mkdir -p /home/daytona/workspace/carb-studyguide && ls /home/daytona/workspace/c…

~/carb-studyguide/generate_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.lib.colors import (HexColor, white, black, Color)
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus.flowables import Flowable
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont
import os

# ── Colors ──────────────────────────────────────────────────────────────────
C_DARK_BLUE   = HexColor('#1a3a5c')
C_MED_BLUE    = HexColor('#2563a8')
C_LIGHT_BLUE  = HexColor('#dbeafe')
C_ACCENT      = HexColor('#e63946')
C_GREEN       = HexColor('#16a34a')
C_GREEN_LIGHT = HexColor('#dcfce7')
C_ORANGE      = HexColor('#ea580c')
C_ORANGE_LIGHT= HexColor('#fff7ed')
C_YELLOW_LIGHT= HexColor('#fefce8')
C_YELLOW      = HexColor('#ca8a04')
C_PURPLE      = HexColor('#7c3aed')
C_PURPLE_LIGHT= HexColor('#f5f3ff')
C_GRAY_LIGHT  = HexColor('#f1f5f9')
C_GRAY_MED    = HexColor('#64748b')
C_GRAY_DARK   = HexColor('#334155')
C_TABLE_HDR   = HexColor('#1e40af')
C_TABLE_ALT   = HexColor('#eff6ff')

W = A4[0] - 2*cm  # usable width

# ── Styles ───────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def S(name, **kw):
    return ParagraphStyle(name, **kw)

TITLE_STYLE = S('Title',
    fontSize=26, textColor=white, fontName='Helvetica-Bold',
    alignment=TA_CENTER, spaceAfter=4)

SUBTITLE_STYLE = S('Subtitle',
    fontSize=12, textColor=HexColor('#bfdbfe'), fontName='Helvetica',
    alignment=TA_CENTER, spaceAfter=2)

H1 = S('H1',
    fontSize=14, textColor=white, fontName='Helvetica-Bold',
    alignment=TA_LEFT, spaceBefore=4, spaceAfter=4,
    leftIndent=0, borderPadding=(6,8,6,8))

H2 = S('H2',
    fontSize=12, textColor=C_DARK_BLUE, fontName='Helvetica-Bold',
    spaceBefore=10, spaceAfter=4, leftIndent=0)

H3 = S('H3',
    fontSize=10.5, textColor=C_MED_BLUE, fontName='Helvetica-Bold',
    spaceBefore=8, spaceAfter=3, leftIndent=0)

BODY = S('Body',
    fontSize=9.5, textColor=C_GRAY_DARK, fontName='Helvetica',
    leading=14, spaceBefore=2, spaceAfter=2, alignment=TA_JUSTIFY)

BODY_BOLD = S('BodyBold',
    fontSize=9.5, textColor=C_GRAY_DARK, fontName='Helvetica-Bold',
    leading=14, spaceBefore=2, spaceAfter=2)

BULLET = S('Bullet',
    fontSize=9.5, textColor=C_GRAY_DARK, fontName='Helvetica',
    leading=14, spaceBefore=1, spaceAfter=1,
    leftIndent=14, bulletIndent=4)

BULLET2 = S('Bullet2',
    fontSize=9, textColor=C_GRAY_DARK, fontName='Helvetica',
    leading=13, spaceBefore=1, spaceAfter=1,
    leftIndent=28, bulletIndent=18)

NOTE = S('Note',
    fontSize=9, textColor=C_ORANGE, fontName='Helvetica-BoldOblique',
    leading=13, spaceBefore=3, spaceAfter=3,
    leftIndent=10, borderPadding=4)

MNEMONIC = S('Mnemonic',
    fontSize=9.5, textColor=C_PURPLE, fontName='Helvetica-Bold',
    leading=14, spaceBefore=2, spaceAfter=2,
    leftIndent=10)

CODE = S('Code',
    fontSize=8.5, textColor=C_DARK_BLUE, fontName='Courier-Bold',
    leading=12, spaceBefore=1, spaceAfter=1,
    leftIndent=20)

CAPTION = S('Caption',
    fontSize=8, textColor=C_GRAY_MED, fontName='Helvetica-Oblique',
    alignment=TA_CENTER, spaceBefore=2, spaceAfter=4)

# ── Helper Flowables ─────────────────────────────────────────────────────────
class ColorBox(Flowable):
    """A colored rectangle used as section header background."""
    def __init__(self, text, bg_color, text_color=white, height=28, fontsize=13):
        Flowable.__init__(self)
        self.text = text
        self.bg_color = bg_color
        self.text_color = text_color
        self.height = height
        self.fontsize = fontsize
        self.width = W

    def draw(self):
        c = self.canv
        c.setFillColor(self.bg_color)
        c.roundRect(0, 0, self.width, self.height, 5, fill=1, stroke=0)
        c.setFillColor(self.text_color)
        c.setFont('Helvetica-Bold', self.fontsize)
        c.drawString(10, 8, self.text)

    def wrap(self, *args):
        return (self.width, self.height + 4)

class InfoBox(Flowable):
    """Colored info/alert box."""
    def __init__(self, lines, bg_color, border_color, label='', width=None):
        Flowable.__init__(self)
        self.lines = lines
        self.bg_color = bg_color
        self.border_color = border_color
        self.label = label
        self._width = width or W

    def wrap(self, avail_w, avail_h):
        self.width = self._width
        self.height = 14 * len(self.lines) + 16
        return (self.width, self.height)

    def draw(self):
        c = self.canv
        h = self.height
        c.setFillColor(self.bg_color)
        c.roundRect(0, 0, self.width, h, 5, fill=1, stroke=0)
        c.setStrokeColor(self.border_color)
        c.setLineWidth(1.5)
        c.roundRect(0, 0, self.width, h, 5, fill=0, stroke=1)
        c.setFillColor(self.border_color)
        if self.label:
            c.setFont('Helvetica-Bold', 9)
            c.drawString(10, h - 14, self.label)
        c.setFillColor(C_GRAY_DARK)
        c.setFont('Helvetica', 9)
        for i, line in enumerate(self.lines):
            y = h - 14 - (14 * i) - (14 if self.label else 0)
            if line.startswith('**') and line.endswith('**'):
                c.setFont('Helvetica-Bold', 9)
                c.drawString(12, y, line.strip('*'))
                c.setFont('Helvetica', 9)
            else:
                c.drawString(12, y, line)

def sp(h=4):
    return Spacer(1, h)

def hr(color=C_LIGHT_BLUE):
    return HRFlowable(width='100%', thickness=1, color=color, spaceAfter=4, spaceBefore=4)

def make_table(data, col_widths=None, header_bg=C_TABLE_HDR, alt_bg=C_TABLE_ALT):
    style = TableStyle([
        ('BACKGROUND',   (0,0), (-1,0), header_bg),
        ('TEXTCOLOR',    (0,0), (-1,0), white),
        ('FONTNAME',     (0,0), (-1,0), 'Helvetica-Bold'),
        ('FONTSIZE',     (0,0), (-1,0), 9),
        ('FONTNAME',     (0,1), (-1,-1), 'Helvetica'),
        ('FONTSIZE',     (0,1), (-1,-1), 8.5),
        ('TEXTCOLOR',    (0,1), (-1,-1), C_GRAY_DARK),
        ('ROWBACKGROUNDS',(0,1),(-1,-1), [white, alt_bg]),
        ('GRID',         (0,0), (-1,-1), 0.5, HexColor('#cbd5e1')),
        ('VALIGN',       (0,0), (-1,-1), 'MIDDLE'),
        ('LEFTPADDING',  (0,0), (-1,-1), 6),
        ('RIGHTPADDING', (0,0), (-1,-1), 6),
        ('TOPPADDING',   (0,0), (-1,-1), 4),
        ('BOTTOMPADDING',(0,0), (-1,-1), 4),
        ('ROWBACKGROUNDS',(0,0),(-1,0), [header_bg]),
    ])
    t = Table(data, colWidths=col_widths, repeatRows=1)
    t.setStyle(style)
    return t

def two_col_table(left_data, right_data, left_w=None, right_w=None):
    """Place two tables side by side."""
    lw = left_w or W*0.48
    rw = right_w or W*0.48
    gap = W - lw - rw
    combined = Table([[left_data, Spacer(gap, 1), right_data]],
                     colWidths=[lw, gap, rw])
    combined.setStyle(TableStyle([
        ('VALIGN', (0,0), (-1,-1), 'TOP'),
        ('LEFTPADDING', (0,0), (-1,-1), 0),
        ('RIGHTPADDING', (0,0), (-1,-1), 0),
    ]))
    return combined

# ── Cover page builder ───────────────────────────────────────────────────────
class CoverPage(Flowable):
    def __init__(self, width, height):
        Flowable.__init__(self)
        self.pg_width = width
        self.pg_height = height

    def wrap(self, *args):
        return (self.pg_width, self.pg_height)

    def draw(self):
        c = self.canv
        w, h = self.pg_width, self.pg_height
        # background gradient simulation
        c.setFillColor(C_DARK_BLUE)
        c.rect(0, 0, w, h, fill=1, stroke=0)
        # accent strip
        c.setFillColor(C_MED_BLUE)
        c.rect(0, h*0.35, w, h*0.3, fill=1, stroke=0)
        # decorative circles
        c.setFillColor(HexColor('#ffffff15'))
        c.circle(w*0.85, h*0.8, 120, fill=1, stroke=0)
        c.circle(w*0.1, h*0.15, 80, fill=1, stroke=0)
        # Title
        c.setFillColor(white)
        c.setFont('Helvetica-Bold', 32)
        c.drawCentredString(w/2, h*0.62, 'CARBOHYDRATES &')
        c.drawCentredString(w/2, h*0.55, 'GLUCOSE METABOLISM')
        # Subtitle
        c.setFont('Helvetica', 14)
        c.setFillColor(HexColor('#bfdbfe'))
        c.drawCentredString(w/2, h*0.48, 'Complete Study Guide')
        # divider
        c.setStrokeColor(C_ACCENT)
        c.setLineWidth(3)
        c.line(w*0.2, h*0.44, w*0.8, h*0.44)
        # Topics
        c.setFont('Helvetica-Bold', 10)
        c.setFillColor(white)
        topics = [
            '• Classification of Carbohydrates',
            '• Glycolysis & Energetics',
            '• TCA Cycle (Krebs Cycle)',
            '• HMP Shunt / Pentose Phosphate Pathway',
            '• Gluconeogenesis & Glycogenesis',
            '• Blood Glucose Regulation',
            '• Glucose Tolerance Test (GTT)',
            '• Glycosuria & Clinical Conditions',
        ]
        y = h*0.40
        for t in topics:
            c.drawCentredString(w/2, y, t)
            y -= 18
        # footer
        c.setFont('Helvetica', 9)
        c.setFillColor(HexColor('#94a3b8'))
        c.drawCentredString(w/2, 30, 'Sources: Basic Medical Biochemistry 6e  |  Guyton & Hall Physiology  |  Tietz Laboratory Medicine 7e')

# ── Build Story ───────────────────────────────────────────────────────────────
def build():
    path = '/home/daytona/workspace/carb-studyguide/Carbohydrates_Glucose_Metabolism_StudyGuide.pdf'
    doc = SimpleDocTemplate(
        path, pagesize=A4,
        leftMargin=1*cm, rightMargin=1*cm,
        topMargin=1.2*cm, bottomMargin=1.2*cm,
        title='Carbohydrates & Glucose Metabolism Study Guide',
        author='Orris Medical'
    )

    story = []

    # ── COVER ─────────────────────────────────────────────────────────────────
    story.append(CoverPage(A4[0], A4[1]))
    story.append(PageBreak())

    # ── SECTION 1: Classification ─────────────────────────────────────────────
    story.append(ColorBox('1.  CLASSIFICATION OF CARBOHYDRATES', C_DARK_BLUE))
    story.append(sp(6))

    story.append(Paragraph('Carbohydrates are polyhydroxy aldehydes or ketones - basically sugar molecules of different sizes.', BODY))
    story.append(sp(4))

    # Monosaccharides
    story.append(Paragraph('Monosaccharides  (Single sugar unit - cannot be broken down further)', H2))
    data = [['Sugar', 'Type', 'Key Role'],
            ['Glucose', 'Aldohexose', 'Primary fuel of the body'],
            ['Fructose', 'Ketohexose', 'Fruit sugar; enters glycolysis as F6P'],
            ['Galactose', 'Aldohexose', 'Milk sugar component'],
            ['Ribose', 'Aldopentose', 'Backbone of RNA, ATP, NAD+'],
            ['Deoxyribose', 'Deoxypentose', 'Backbone of DNA']]
    story.append(make_table(data, col_widths=[W*0.25, W*0.25, W*0.5]))
    story.append(sp(6))

    # Disaccharides
    story.append(Paragraph('Disaccharides  (Two monosaccharide units)', H2))
    data = [['Name', 'Components', 'Bond', 'Source'],
            ['Sucrose', 'Glucose + Fructose', 'α1,β2', 'Table sugar'],
            ['Lactose', 'Glucose + Galactose', 'β1,4', 'Milk (lactase deficiency = bloating)'],
            ['Maltose', 'Glucose + Glucose', 'α1,4', 'Malt, starch digestion product']]
    story.append(make_table(data, col_widths=[W*0.18, W*0.28, W*0.14, W*0.40]))
    story.append(sp(6))

    # Polysaccharides
    story.append(Paragraph('Polysaccharides  (Many sugar units)', H2))
    story.append(Paragraph('<b>A. Homopolysaccharides</b> — all units are the SAME monosaccharide', H3))
    data = [['Name', 'Monomer', 'Linkage', 'Location / Function'],
            ['Starch (Amylose)', 'Glucose', 'α-1,4', 'Plant storage; linear chain'],
            ['Starch (Amylopectin)', 'Glucose', 'α-1,4 + α-1,6 branches', 'Plant storage; branched (every 24-30 units)'],
            ['Glycogen', 'Glucose', 'α-1,4 + α-1,6 branches', 'Animal storage; liver & muscle (more branched)'],
            ['Cellulose', 'Glucose', 'β-1,4', 'Plant cell wall; not digestible by humans'],
            ['Dextran', 'Glucose', 'α-1,6', 'Bacterial; used as plasma volume expander'],
            ['Inulin', 'Fructose', 'β-2,1', 'Lab: used to measure GFR (freely filtered, not reabsorbed)'],
            ['Chitin', 'N-Acetylglucosamine', 'β-1,4', 'Insect exoskeletons, fungal cell walls']]
    story.append(make_table(data, col_widths=[W*0.22, W*0.18, W*0.22, W*0.38]))
    story.append(sp(8))

    story.append(Paragraph('<b>B. Mucopolysaccharides (Glycosaminoglycans / GAGs)</b> — alternating disaccharide units, highly negatively charged, attract water → form gel-like ground substance of connective tissue', H3))
    data = [['GAG', 'Composition', 'Key Location', 'Function'],
            ['Hyaluronic acid', 'GlcUA + GlcNAc', 'Synovial fluid, vitreous humor', 'Lubrication, shock absorption'],
            ['Chondroitin sulfate', 'GlcUA + GalNAc-SO4', 'Cartilage, bone, cornea', 'Structural support'],
            ['Dermatan sulfate', 'IdoUA + GalNAc-SO4', 'Skin, blood vessels', 'Structural, anticoagulant'],
            ['Heparin / Heparan sulfate', 'IdoUA/GlcUA + GlcNH2', 'Mast cells, blood vessel walls', 'Anticoagulant (activates antithrombin III)'],
            ['Keratan sulfate', 'Galactose + GlcNAc-SO4', 'Cornea, cartilage, bone', 'Corneal transparency']]
    story.append(make_table(data, col_widths=[W*0.22, W*0.25, W*0.28, W*0.25]))
    story.append(sp(4))
    story.append(InfoBox(
        ['⚠  CLINICAL: Mucopolysaccharidoses — deficiency of lysosomal enzymes that degrade GAGs',
         '   → GAGs accumulate in tissues → coarse facies, organomegaly, skeletal deformity, mental retardation',
         '   Hurler syndrome: deficiency of α-L-iduronidase (AR) | Hunter syndrome: iduronate sulfatase (XR)'],
        C_ORANGE_LIGHT, C_ORANGE, ''))
    story.append(PageBreak())

    # ── SECTION 2: Fate of Glucose ────────────────────────────────────────────
    story.append(ColorBox('2.  FATE OF GLUCOSE IN THE BODY', C_MED_BLUE))
    story.append(sp(6))
    story.append(Paragraph('After absorption from the gut, glucose in the blood can take 6 pathways:', BODY))
    story.append(sp(4))
    fate_data = [
        ['Pathway', 'Product', 'Where', 'When'],
        ['Glycolysis → TCA → OXPHOS', '~30-32 ATP', 'All cells', 'Always (primary energy source)'],
        ['Glycogenesis', 'Glycogen', 'Liver, Muscle', 'Fed state (high insulin)'],
        ['Pentose Phosphate (HMP Shunt)', 'NADPH + Ribose-5-P', 'Liver, RBCs, Adrenal', 'For biosynthesis + antioxidant'],
        ['Lipogenesis', 'Triglycerides', 'Liver, Adipose', 'Excess glucose; fed state'],
        ['Glucuronate pathway', 'Glucuronic acid', 'Liver', 'Detoxification, GAG synthesis'],
        ['Excretion in urine (Glycosuria)', 'None', 'Kidney', 'Only if blood glucose > 180 mg/dL'],
    ]
    story.append(make_table(fate_data, col_widths=[W*0.30, W*0.22, W*0.22, W*0.26]))
    story.append(PageBreak())

    # ── SECTION 3: Glycolysis ─────────────────────────────────────────────────
    story.append(ColorBox('3.  GLYCOLYSIS — Pathway & Energetics', C_DARK_BLUE))
    story.append(sp(6))
    story.append(Paragraph('<b>Definition:</b> Breakdown of 1 glucose (6C) → 2 pyruvate (3C) | Location: Cytosol | Works with OR without O₂', BODY))
    story.append(sp(8))

    story.append(Paragraph('PHASE 1 — Investment Phase (spends 2 ATP)', H2))
    p1_data = [
        ['Step', 'Reaction', 'Enzyme', 'Key Points'],
        ['1', 'Glucose → Glucose-6-P', 'Hexokinase (all tissues)\nGlucokinase (liver, β-cells)', 'Uses 1 ATP; traps glucose; irreversible; Glucokinase: high Km, not saturated at normal glucose'],
        ['2', 'G6P → Fructose-6-P', 'Phosphoglucose isomerase', 'Reversible; isomerization'],
        ['3', 'F6P → Fructose-1,6-BP', 'Phosphofructokinase-1 (PFK-1)', '★ RATE-LIMITING STEP; uses 1 ATP; irreversible\nActivated by: AMP, ADP, F-2,6-BP, insulin\nInhibited by: ATP, citrate, glucagon'],
        ['4', 'F-1,6-BP → DHAP + G3P', 'Aldolase', 'Splits 6C into two 3C fragments'],
        ['5', 'DHAP ⇌ G3P', 'Triose phosphate isomerase', 'DHAP converted to G3P → both enter Phase 2'],
    ]
    story.append(make_table(p1_data, col_widths=[W*0.06, W*0.28, W*0.26, W*0.40]))
    story.append(sp(8))

    story.append(Paragraph('PHASE 2 — Payoff Phase (all steps × 2, earns 4 ATP + 2 NADH)', H2))
    p2_data = [
        ['Step', 'Reaction', 'Enzyme', 'Key Points'],
        ['6', 'G3P → 1,3-Bisphosphoglycerate', 'G3P Dehydrogenase', 'Oxidation step; produces 2 NADH (×2); uses inorganic phosphate'],
        ['7', '1,3-BPG → 3-Phosphoglycerate', 'Phosphoglycerate kinase', '2 ATP produced (×2) — substrate-level phosphorylation'],
        ['8', '3-PG → 2-Phosphoglycerate', 'Phosphoglycerate mutase', 'Shifts phosphate group'],
        ['9', '2-PG → PEP', 'Enolase', 'Inhibited by fluoride (used in fluoride tubes!)'],
        ['10', 'PEP → Pyruvate', 'Pyruvate kinase', '2 ATP produced (×2); irreversible\nInhibited by: ATP, alanine\nActivated by: F-1,6-BP (feedforward)'],
    ]
    story.append(make_table(p2_data, col_widths=[W*0.06, W*0.28, W*0.24, W*0.42]))
    story.append(sp(8))

    story.append(Paragraph('Net Energetics of Glycolysis', H2))
    net_data = [
        ['Product', 'Amount', 'Notes'],
        ['ATP (net)', '2 ATP', 'Substrate-level phosphorylation'],
        ['NADH', '2 NADH', '5 ATP if via malate-aspartate shuttle; 3 ATP via G3P shuttle'],
        ['Pyruvate', '2 molecules', 'Further oxidized aerobically or reduced to lactate anaerobically'],
    ]
    story.append(make_table(net_data, col_widths=[W*0.25, W*0.20, W*0.55]))
    story.append(sp(6))

    story.append(Paragraph('Fate of Pyruvate', H3))
    fate_pyr = [
        ['Condition', 'Product', 'Enzyme', 'Significance'],
        ['Aerobic (O₂ present)', 'Acetyl-CoA + CO₂ + NADH', 'Pyruvate Dehydrogenase Complex\n(needs: TPP, lipoate, CoA, FAD, NAD+)', 'Enters TCA cycle → ~28 more ATP'],
        ['Anaerobic (no O₂)', 'Lactate + NAD+', 'Lactate Dehydrogenase (LDH)', 'Regenerates NAD+ → glycolysis continues; Cori cycle sends lactate to liver'],
        ['In liver/yeast', 'Acetaldehyde → Ethanol', 'Pyruvate decarboxylase → Alcohol DH', 'Alcoholic fermentation'],
    ]
    story.append(make_table(fate_pyr, col_widths=[W*0.22, W*0.30, W*0.26, W*0.22]))
    story.append(sp(4))
    story.append(InfoBox(
        ['★ Mnemonic for Glycolysis steps:',
         '   "Goodness Gracious, Father Franklin Did Go By Picking Peas"',
         '   Glucose → G6P → F6P → F1,6BP → (DHAP+G3P) → 1,3BPG → 3PG → 2PG → PEP → Pyruvate'],
        C_PURPLE_LIGHT, C_PURPLE, ''))
    story.append(PageBreak())

    # ── SECTION 4: TCA Cycle ──────────────────────────────────────────────────
    story.append(ColorBox('4.  TCA CYCLE (Krebs Cycle / Citric Acid Cycle)', C_GREEN))
    story.append(sp(6))
    story.append(Paragraph('<b>Location:</b> Mitochondrial matrix  |  <b>Entry substrate:</b> Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C)', BODY))
    story.append(sp(6))

    tca_data = [
        ['#', 'Reaction', 'Enzyme', 'Product', 'Notes'],
        ['1', 'Acetyl-CoA + OAA → Citrate', 'Citrate Synthase', '—', 'Condensation; inhibited by ATP, NADH, succinyl-CoA'],
        ['2', 'Citrate → Isocitrate', 'Aconitase', '—', 'Isomerization via aconitate; inhibited by fluoroacetate'],
        ['3', 'Isocitrate → α-Ketoglutarate', 'Isocitrate Dehydrogenase', 'NADH + CO₂', '★ RATE-LIMITING; activated by ADP, Ca²⁺; inhibited by ATP, NADH'],
        ['4', 'α-KG → Succinyl-CoA', 'α-KG Dehydrogenase complex', 'NADH + CO₂', 'Irreversible; same cofactors as PDC; inhibited by NADH, succinyl-CoA'],
        ['5', 'Succinyl-CoA → Succinate', 'Succinyl-CoA Synthetase', 'GTP (or ATP)', 'Only substrate-level phosphorylation in TCA'],
        ['6', 'Succinate → Fumarate', 'Succinate Dehydrogenase', 'FADH₂', 'Only FAD-linked TCA enzyme; embedded in inner membrane (Complex II)'],
        ['7', 'Fumarate → Malate', 'Fumarase', 'H₂O added', 'Trans-addition of water'],
        ['8', 'Malate → Oxaloacetate', 'Malate Dehydrogenase', 'NADH', 'OAA regenerated → ready for next turn'],
    ]
    story.append(make_table(tca_data, col_widths=[W*0.04, W*0.28, W*0.22, W*0.12, W*0.34]))
    story.append(sp(8))

    story.append(Paragraph('Energetics per Acetyl-CoA (one turn):', H3))
    e_data = [
        ['Product', 'Amount', 'ATP Equivalent'],
        ['NADH', '3', '3 × 2.5 = 7.5 ATP'],
        ['FADH₂', '1', '1 × 1.5 = 1.5 ATP'],
        ['GTP', '1', '1 ATP'],
        ['TOTAL', '', '≈ 10 ATP per Acetyl-CoA'],
    ]
    story.append(make_table(e_data, col_widths=[W*0.30, W*0.20, W*0.50]))
    story.append(sp(6))

    story.append(Paragraph('Importance / Functions of TCA Cycle', H3))
    imp = [
        '1. Primary source of NADH and FADH₂ → drives oxidative phosphorylation → most body ATP',
        '2. Amphibolic pathway: catabolism + anabolism (both breakdown and synthesis)',
        '3. Provides biosynthetic precursors: OAA → aspartate/amino acids; α-KG → glutamate; Succinyl-CoA → heme synthesis; Citrate → exported for fatty acid synthesis',
        '4. Two CO₂ released per turn → exhaled',
        '5. Anaplerotic reactions replenish intermediates (e.g., Pyruvate Carboxylase: Pyr + CO₂ → OAA)',
        '6. Ca²⁺ activates three key enzymes → coupling muscle contraction to energy production',
    ]
    for i in imp:
        story.append(Paragraph(i, BULLET))
    story.append(sp(4))
    story.append(InfoBox(
        ['★ Mnemonic for TCA intermediates:',
         '   "Citrate Is Krebs\' Starting Substrate For Making OAA"',
         '   Citrate → Isocitrate → α-Ketoglutarate → Succinyl-CoA → Succinate → Fumarate → Malate → OAA'],
        C_GREEN_LIGHT, C_GREEN, ''))
    story.append(PageBreak())

    # ── SECTION 5: HMP Shunt ──────────────────────────────────────────────────
    story.append(ColorBox('5.  HMP SHUNT  (Hexose Monophosphate / Pentose Phosphate Pathway)', HexColor('#7c3aed')))
    story.append(sp(6))
    story.append(Paragraph('<b>Location:</b> Cytosol  |  <b>Active in:</b> Liver, RBCs, Adrenal cortex, Gonads, Lactating mammary gland', BODY))
    story.append(Paragraph('<b>Purpose:</b> NOT for ATP. For NADPH production (antioxidant + biosynthesis) and Ribose-5-P (nucleotide synthesis).', BODY))
    story.append(sp(8))

    story.append(Paragraph('Phase 1 — Oxidative Phase (IRREVERSIBLE) → Generates NADPH', H2))
    ox_data = [
        ['Step', 'Reaction', 'Enzyme', 'Products'],
        ['1', 'Glucose-6-P → 6-Phosphogluconolactone', 'G6P Dehydrogenase (★ Rate-limiting)', 'NADPH'],
        ['2', '6-Phosphogluconolactone → 6-Phosphogluconate', 'Lactonase', 'H₂O'],
        ['3', '6-Phosphogluconate → Ribulose-5-P + CO₂', '6-Phosphogluconate Dehydrogenase', 'NADPH + CO₂'],
    ]
    story.append(make_table(ox_data, col_widths=[W*0.06, W*0.40, W*0.30, W*0.24]))
    story.append(Paragraph('Net per G6P in oxidative phase: 2 NADPH + 1 CO₂ + Ribulose-5-P', BODY_BOLD))
    story.append(sp(8))

    story.append(Paragraph('Phase 2 — Non-Oxidative Phase (REVERSIBLE) → Interconverts sugars', H2))
    story.append(Paragraph('Transketolase and Transaldolase reactions shuffle C3-C7 sugar phosphates. Products can re-enter glycolysis as F6P and G3P, or be used for nucleotide synthesis.', BODY))
    story.append(sp(8))

    story.append(Paragraph('Functions of NADPH', H3))
    nadph_data = [
        ['Function', 'Details'],
        ['RBC protection', 'Reduces glutathione (GSSG → GSH) → neutralises H₂O₂ via glutathione peroxidase → prevents oxidative haemolysis'],
        ['Fatty acid synthesis', 'Required by Fatty Acid Synthase complex in liver and adipose'],
        ['Cholesterol synthesis', 'Required by HMG-CoA reductase pathway'],
        ['Steroid hormone synthesis', 'P450 enzymes in adrenal cortex need NADPH'],
        ['Phagocyte killing', 'NADPH oxidase produces O₂⁻ (superoxide) → oxidative burst to kill bacteria'],
        ['Detoxification', 'Cytochrome P450 enzymes in liver use NADPH'],
    ]
    story.append(make_table(nadph_data, col_widths=[W*0.30, W*0.70]))
    story.append(sp(6))
    story.append(InfoBox(
        ['⚠  G6PD Deficiency — Most common enzyme deficiency worldwide (X-linked recessive)',
         '   No G6PD → no NADPH → RBCs unprotected → oxidative stress → hemolytic anemia',
         '   Triggers: Primaquine, Dapsone, Sulfonamides, Nitrofurantoin, Fava beans, Infections',
         '   Blood film: Heinz bodies (denatured Hb), bite cells | Test: G6PD enzyme assay'],
        C_ORANGE_LIGHT, C_ORANGE, ''))
    story.append(PageBreak())

    # ── SECTION 6: Gluconeogenesis ────────────────────────────────────────────
    story.append(ColorBox('6.  GLUCONEOGENESIS', C_DARK_BLUE))
    story.append(sp(6))
    story.append(Paragraph('<b>Definition:</b> Synthesis of glucose from non-carbohydrate precursors. Occurs mainly in <b>liver</b> (90%) and <b>kidney</b> (10%, important in prolonged fasting/acidosis).', BODY))
    story.append(Paragraph('<b>When:</b> Fasting > 4-6h (after liver glycogen falls), prolonged exercise, stress, starvation', BODY))
    story.append(sp(6))

    story.append(Paragraph('Non-Carbohydrate Precursors (Sources of Glucose)', H2))
    prec_data = [
        ['Precursor', 'How it enters', 'Source', 'Clinical Relevance'],
        ['Lactate', 'Lactate → Pyruvate (LDH) → gluconeogenesis', 'Anaerobic muscle, RBCs', 'Cori Cycle: lactate shuttled to liver'],
        ['Alanine', 'Alanine → Pyruvate (ALT/transamination)', 'Muscle protein catabolism', 'Alanine Cycle: key during fasting/starvation'],
        ['Glutamine', 'Glutamine → α-KG (TCA) → OAA → PEP', 'Muscle, gut', 'Important in kidney during acidosis'],
        ['Glycerol', 'Glycerol → DHAP (via G3P)', 'Lipolysis of triglycerides', 'Fat stores provide ~10% of gluconeogenesis substrate'],
        ['Propionate', 'Propionate → Succinyl-CoA → OAA → PEP', 'Odd-chain fatty acid β-oxidation', 'Only fatty acid precursor for glucose'],
    ]
    story.append(make_table(prec_data, col_widths=[W*0.18, W*0.27, W*0.22, W*0.33]))
    story.append(Paragraph('❌  Even-chain fatty acids CANNOT generate net glucose (Acetyl-CoA → TCA → CO₂, net carbon balance = 0)', NOTE))
    story.append(sp(8))

    story.append(Paragraph('The Three Unique Steps of Gluconeogenesis (Bypass Reactions)', H2))
    bypass_data = [
        ['Glycolytic Enzyme\n(IRREVERSIBLE)', 'Problem', 'Gluconeogenic Bypass\nEnzyme(s)', 'Location + Cofactors'],
        ['Pyruvate Kinase\n(PEP → Pyruvate)', 'Cannot reverse PEP → Pyr', 'Step 1: Pyruvate Carboxylase\n(Pyruvate + CO₂ → OAA)\nStep 2: PEPCK\n(OAA → PEP + CO₂)', 'PC: mitochondria, needs Biotin + ATP\nPEPCK: cytosol, needs GTP'],
        ['PFK-1\n(F6P → F-1,6-BP)', 'Cannot reverse F6P → F-1,6-BP', 'Fructose-1,6-Bisphosphatase\n(F-1,6-BP → F6P)', 'Cytosol; inhibited by AMP, F-2,6-BP\nActivated by citrate'],
        ['Hexokinase/Glucokinase\n(Glucose → G6P)', 'Cannot reverse glucose → G6P', 'Glucose-6-Phosphatase\n(G6P → Glucose)', 'ER membrane; ONLY in liver + kidney\n(NOT in muscle or brain!)'],
    ]
    story.append(make_table(bypass_data, col_widths=[W*0.22, W*0.22, W*0.28, W*0.28]))
    story.append(sp(6))

    story.append(Paragraph('Regulation of Gluconeogenesis', H3))
    reg_gneg = [
        ['Regulator', 'Effect', 'Mechanism'],
        ['Insulin (fed state)', 'INHIBITS', '↓ PEPCK expression, ↑ PFK-2 activity → ↑ F-2,6-BP → inhibits FBPase-1'],
        ['Glucagon (fasting)', 'ACTIVATES', 'cAMP → PKA → activates FBPase-2 → ↓ F-2,6-BP → removes inhibition of FBPase-1'],
        ['Cortisol', 'ACTIVATES', 'Induces PEPCK, FBPase-1; provides amino acid substrates from muscle proteolysis'],
        ['Acetyl-CoA', 'ACTIVATES (allosteric)', 'Activates Pyruvate Carboxylase → ↑ OAA → drives gluconeogenesis'],
        ['AMP', 'INHIBITS FBPase-1', 'Allosteric inhibition → blocks gluconeogenesis (promotes glycolysis instead)'],
    ]
    story.append(make_table(reg_gneg, col_widths=[W*0.22, W*0.16, W*0.62]))
    story.append(sp(4))
    story.append(InfoBox(
        ['★ Mnemonic for gluconeogenic precursors: "GOAL"',
         '   G = Glycerol  |  O = Odd-chain fatty acids  |  A = Amino acids  |  L = Lactate'],
        C_PURPLE_LIGHT, C_PURPLE, ''))
    story.append(PageBreak())

    # ── SECTION 7: Glycogenesis ───────────────────────────────────────────────
    story.append(ColorBox('7.  GLYCOGENESIS  (Glycogen Synthesis)', C_MED_BLUE))
    story.append(sp(6))
    story.append(Paragraph('<b>Definition:</b> Synthesis of glycogen from glucose for storage. Occurs in <b>liver</b> (blood glucose maintenance) and <b>skeletal muscle</b> (local energy reserve).', BODY))
    story.append(sp(6))

    story.append(Paragraph('Steps of Glycogenesis', H2))
    gly_data = [
        ['Step', 'Reaction', 'Enzyme', 'Key Detail'],
        ['1', 'Glucose → Glucose-6-Phosphate', 'Hexokinase (muscle)\nGlucokinase (liver)', 'Uses 1 ATP; traps glucose'],
        ['2', 'G6P → Glucose-1-Phosphate', 'Phosphoglucomutase', 'Prepares for activation'],
        ['3', 'G1P + UTP → UDP-Glucose + PPi', 'UDP-Glucose Pyrophosphorylase', '"Activated glucose" — high-energy form ready to be added to chain'],
        ['4', 'UDP-Glucose → Glycogen (elongation)', 'Glycogen Synthase ★', 'Adds glucose via α-1,4 bonds to non-reducing ends; needs glycogenin primer (≥4 glucose units)'],
        ['5', 'Branch creation (every ~11 residues)', 'Branching Enzyme\n(Amylo-1,4→1,6 glucan transferase)', 'Moves 6-7 glucose block to create α-1,6 branch point; ↑ solubility, ↑ free ends for faster mobilization'],
    ]
    story.append(make_table(gly_data, col_widths=[W*0.06, W*0.28, W*0.26, W*0.40]))
    story.append(sp(8))

    story.append(Paragraph('Regulation of Glycogen Synthase', H3))
    gs_data = [
        ['State', 'Signal', 'Effect on Glycogen Synthase', 'Result'],
        ['Fed (post-meal)', 'Insulin ↑', 'Protein phosphatase dephosphorylates → ACTIVE form', 'Glycogen stored'],
        ['Fasting/Stress', 'Glucagon/Epinephrine ↑', 'PKA phosphorylates → INACTIVE (b) form', 'Glycogen breakdown'],
        ['Muscle (local)', 'Glucose-6-P ↑', 'Allosteric activation of inactive form', 'Glycogen stored locally'],
    ]
    story.append(make_table(gs_data, col_widths=[W*0.16, W*0.20, W*0.36, W*0.28]))
    story.append(sp(4))
    story.append(InfoBox(
        ['★ Key rule: Glycogen Synthase is ACTIVE when DEPHOSPHORYLATED (insulin activates phosphatase)',
         '   Glycogen Phosphorylase (breakdown) is ACTIVE when PHOSPHORYLATED (glucagon/epinephrine activates PKA)',
         '   These two pathways are reciprocally regulated — can\'t synthesize and break down simultaneously'],
        C_LIGHT_BLUE, C_MED_BLUE, ''))
    story.append(PageBreak())

    # ── SECTION 8: Blood Glucose Regulation ──────────────────────────────────
    story.append(ColorBox('8.  BLOOD GLUCOSE REGULATION', C_DARK_BLUE))
    story.append(sp(6))

    story.append(Paragraph('Normal Values — Must Know!', H2))
    bgl_data = [
        ['Condition', 'Blood Glucose Level', 'Significance'],
        ['Normal fasting (8h)', '70–100 mg/dL (3.9–5.6 mmol/L)', 'Standard reference range'],
        ['2h post-meal (OGTT)', '< 140 mg/dL (< 7.8 mmol/L)', 'Normal postprandial'],
        ['Impaired fasting glucose', '100–125 mg/dL', 'Pre-diabetes'],
        ['Impaired glucose tolerance', '140–199 mg/dL at 2h OGTT', 'Pre-diabetes'],
        ['Diabetes Mellitus (fasting)', '≥ 126 mg/dL (on 2 occasions)', 'Diagnostic threshold'],
        ['Diabetes Mellitus (2h OGTT)', '≥ 200 mg/dL', 'Diagnostic threshold'],
        ['Renal threshold for glucose', '≈ 180 mg/dL', 'Glucose appears in urine above this'],
        ['Hypoglycemia', '< 70 mg/dL', 'Symptoms: sweating, palpitations, confusion'],
    ]
    story.append(make_table(bgl_data, col_widths=[W*0.30, W*0.35, W*0.35]))
    story.append(sp(8))

    story.append(Paragraph('Hormonal Regulation', H2))
    horm_data = [
        ['Hormone', 'Source', 'Effect on Blood Glucose', 'Key Actions'],
        ['Insulin', 'Pancreatic β-cells', '↓ DECREASES', '↑ GLUT4 (muscle/fat), ↑ glycolysis, ↑ glycogenesis, ↑ lipogenesis; ↓ gluconeogenesis, ↓ glycogenolysis'],
        ['Glucagon', 'Pancreatic α-cells', '↑ INCREASES', '↑ glycogenolysis, ↑ gluconeogenesis; ↓ glycolysis (via ↓ F-2,6-BP)'],
        ['Epinephrine (Adrenaline)', 'Adrenal medulla', '↑ INCREASES', '↑ glycogenolysis (liver + muscle), ↑ gluconeogenesis, ↑ lipolysis; rapid response'],
        ['Cortisol', 'Adrenal cortex', '↑ INCREASES', '↑ gluconeogenesis enzyme expression, ↑ proteolysis (provides substrates), ↓ peripheral glucose uptake'],
        ['Growth Hormone', 'Anterior pituitary', '↑ INCREASES', 'Anti-insulin; ↓ glucose uptake by peripheral tissues, ↑ lipolysis; "diabetogenic"'],
        ['Somatostatin', 'Pancreatic δ-cells', '— Biphasic', 'Inhibits BOTH insulin and glucagon secretion'],
        ['GLP-1 / GIP (Incretins)', 'Gut L-cells / K-cells', '↓ Indirectly decreases', 'Potentiate insulin release in response to glucose; inhibit glucagon; GLP-1 also slows gastric emptying'],
        ['Thyroxine (T₄)', 'Thyroid gland', '↑ INCREASES', '↑ glycogenolysis, ↑ glucose absorption from gut, ↑ basal metabolic rate'],
    ]
    story.append(make_table(horm_data, col_widths=[W*0.18, W*0.18, W*0.16, W*0.48]))
    story.append(sp(8))

    story.append(Paragraph('Response to Hypoglycemia (sequential, layered defense)', H3))
    hypo_data = [
        ['Timeframe', 'Response', 'Mechanism'],
        ['Minutes (1st line)', 'Glucagon ↑', 'Glycogenolysis + gluconeogenesis in liver'],
        ['Minutes (2nd line)', 'Epinephrine ↑', 'Emergency glycogenolysis; also inhibits insulin secretion'],
        ['Hours (3rd line)', 'Growth Hormone ↑\nCortisol ↑', 'Reduce glucose utilisation by peripheral tissues; ↑ gluconeogenesis; ↑ lipolysis'],
        ['All phases', 'Hepatic gluconeogenesis', 'After ~30h fast: glycogen depleted → gluconeogenesis is only source'],
    ]
    story.append(make_table(hypo_data, col_widths=[W*0.22, W*0.25, W*0.53]))
    story.append(sp(4))
    story.append(InfoBox(
        ['★ Key quote from Guyton & Hall:',
         '   "Glucose is the ONLY nutrient that can be used by the brain, retina, and germinal epithelium',
         '    of the gonads in sufficient quantities to supply optimally required energy."',
         '   This is WHY blood glucose regulation is so critical.'],
        C_LIGHT_BLUE, C_MED_BLUE, ''))
    story.append(PageBreak())

    # ── SECTION 9: GTT ───────────────────────────────────────────────────────
    story.append(ColorBox('9.  GLUCOSE TOLERANCE TEST (GTT / OGTT)', C_GREEN))
    story.append(sp(6))
    story.append(Paragraph('<b>Purpose:</b> Assesses the body\'s ability to handle a standard glucose load. Diagnoses DM, pre-diabetes, and gestational diabetes.', BODY))
    story.append(sp(6))

    story.append(Paragraph('Indications for GTT', H2))
    ind = [
        '• Fasting blood glucose borderline (100–125 mg/dL) — suspected pre-diabetes or DM',
        '• Gestational Diabetes Mellitus (GDM) screening: 24–28 weeks of pregnancy (MANDATORY)',
        '• HbA1c unreliable (hemolytic anaemia, hemoglobinopathies, iron deficiency)',
        '• Suspected reactive hypoglycemia',
        '• Discordant fasting and random glucose results',
    ]
    for i in ind:
        story.append(Paragraph(i, BULLET))
    story.append(sp(8))

    story.append(Paragraph('Procedure — Standard 75g OGTT', H2))
    proc_data = [
        ['Step', 'Action', 'Details'],
        ['Preparation (3 days before)', 'Unrestricted diet', 'Must eat ≥ 150g carbohydrates/day for 3 days before test'],
        ['Night before', '8–12 hour fast', 'Water only; no alcohol, no smoking, no exercise'],
        ['Time = 0 min', 'Fasting blood sample drawn', 'Also record symptoms; check urine for glucose'],
        ['Glucose load', 'Drink 75g anhydrous glucose', 'Dissolved in 250–300 mL water; consumed within 5 minutes\n(Children: 1.75 g/kg up to max 75g)'],
        ['Time = 60 min', 'Blood sample drawn', 'Required for GDM diagnosis; optional for adult DM screening'],
        ['Time = 120 min', 'Blood sample drawn', 'Primary diagnostic time point'],
        ['Special: GDM', '75g load (IADPSG) or 100g (CC criteria)', 'Any ONE value ≥ threshold = GDM (IADPSG: F≥92, 1h≥180, 2h≥153 mg/dL)'],
    ]
    story.append(make_table(proc_data, col_widths=[W*0.22, W*0.26, W*0.52]))
    story.append(sp(8))

    story.append(Paragraph('Interpretation — 75g OGTT (ADA Criteria)', H2))
    interp_data = [
        ['Category', 'Fasting', '2-Hour Value', 'Action'],
        ['Normal', '< 100 mg/dL', '< 140 mg/dL', 'Reassure; lifestyle advice'],
        ['Impaired Fasting Glucose (IFG)', '100–125 mg/dL', '—', 'Lifestyle modification; repeat annually'],
        ['Impaired Glucose Tolerance (IGT)', '—', '140–199 mg/dL', 'Pre-diabetes; lifestyle modification, consider Metformin'],
        ['Diabetes Mellitus', '≥ 126 mg/dL', '≥ 200 mg/dL', 'Diagnosis confirmed (if asymptomatic, repeat once)'],
        ['Gestational DM (IADPSG)', 'F ≥ 92', '2h ≥ 153 mg/dL', 'Any ONE value met = GDM (also 1h ≥ 180)'],
    ]
    story.append(make_table(interp_data, col_widths=[W*0.28, W*0.17, W*0.18, W*0.37],
                            header_bg=C_GREEN))
    story.append(sp(6))

    story.append(Paragraph('Special GTT Curves', H3))
    curves_data = [
        ['Curve Type', 'Pattern', 'Cause'],
        ['Normal', 'Peak ~140 mg/dL at 1h; returns < 140 at 2h', 'Normal insulin response'],
        ['Diabetic curve', 'Exaggerated peak; slow return; still elevated at 2h', 'Insulin deficiency or resistance'],
        ['Flat curve', 'Minimal rise after glucose load', 'Malabsorption, Addison\'s disease, hypothyroidism'],
        ['Lag storage / Alimentary curve', 'Very high early peak (> 200) then rapid fall', 'Post-gastrectomy, hyperthyroidism'],
        ['Reactive hypoglycemia', 'Normal rise then falls below 70 mg/dL at 3-5h', 'Excess insulin response; insulinoma'],
    ]
    story.append(make_table(curves_data, col_widths=[W*0.22, W*0.42, W*0.36], header_bg=C_GREEN))
    story.append(PageBreak())

    # ── SECTION 10: Glycosuria ────────────────────────────────────────────────
    story.append(ColorBox('10.  GLYCOSURIA', C_ORANGE))
    story.append(sp(6))
    story.append(Paragraph('<b>Definition:</b> Presence of glucose in the urine. Normally, ALL filtered glucose is reabsorbed in the proximal convoluted tubule (PCT) via SGLT2 (90%) and SGLT1 (10%).', BODY))
    story.append(sp(4))

    story.append(Paragraph('Renal Handling of Glucose', H2))
    rh_data = [
        ['Concept', 'Value / Details'],
        ['Renal threshold for glucose', '≈ 180 mg/dL plasma glucose (range 160–200)'],
        ['Tubular maximum (Tm) for glucose', '≈ 375 mg/min (range 300–450 mg/min)'],
        ['Normal urinary glucose', '< 0.8 mmol/L (essentially absent on dipstick)'],
        ['Mechanism of reabsorption', 'PCT: SGLT2 (low affinity, high capacity) + SGLT1 (high affinity, low capacity)'],
        ['Splay in titration curve', 'Not all nephrons have same Tm → glycosuria starts before theoretical Tm is reached'],
    ]
    story.append(make_table(rh_data, col_widths=[W*0.40, W*0.60]))
    story.append(sp(8))

    story.append(Paragraph('Causes of Glycosuria', H2))
    gly_cause = [
        ['Type', 'Blood Glucose', 'Cause', 'Examples'],
        ['Hyperglycaemic\n(overflow glycosuria)', 'HIGH\n(> 180 mg/dL)', 'Blood glucose exceeds Tm → glucose spills', 'DM, Cushing\'s syndrome, acromegaly, pheochromocytoma, steroid therapy, pancreatitis, stress hyperglycaemia'],
        ['Renal glycosuria\n(normoglycaemic)', 'NORMAL', 'Reduced renal threshold OR Tm defect', 'Benign renal glycosuria (SGLT2 mutation), Fanconi syndrome, SGLT2 inhibitor drugs (gliflozins)'],
        ['Physiological\n(pregnancy)', 'NORMAL or mildly ↑', 'Increased GFR + reduced threshold', 'Normal in pregnancy; must rule out GDM'],
        ['Alimentary glycosuria', 'Post-meal SPIKE', 'Rapid absorption overwhelms threshold transiently', 'Post-gastrectomy, rapid gastric emptying'],
    ]
    story.append(make_table(gly_cause, col_widths=[W*0.20, W*0.16, W*0.24, W*0.40],
                            header_bg=C_ORANGE))
    story.append(sp(8))

    story.append(Paragraph('Tests for Glycosuria', H3))
    test_data = [
        ['Test', 'Principle', 'Detects', 'Clinical Use'],
        ['Glucose oxidase dipstick\n(specific)', 'Enzyme-specific for glucose', 'Glucose ONLY', 'Routine DM monitoring; most common'],
        ['Benedict\'s / Fehling\'s test\n(non-specific)', 'Reduces Cu²⁺ (blue→brick red)', 'ALL reducing sugars\n(glucose, galactose, fructose, lactose)', 'Neonatal metabolic screening; detects galactosemia'],
        ['Clinitest tablets', 'Chemical reduction method', 'All reducing sugars', 'Now largely replaced by dipstick'],
    ]
    story.append(make_table(test_data, col_widths=[W*0.24, W*0.22, W*0.22, W*0.32],
                            header_bg=C_ORANGE))
    story.append(sp(4))
    story.append(InfoBox(
        ['⚠  IMPORTANT: In Galactosaemia (newborn) — Benedict\'s test POSITIVE but glucose dipstick NEGATIVE',
         '   Because galactose (not glucose) is the reducing sugar present in urine!',
         '   Also in Fanconi syndrome: glycosuria + aminoaciduria + phosphaturia + uricosuria (generalised PCT defect)'],
        C_ORANGE_LIGHT, C_ORANGE, ''))
    story.append(PageBreak())

    # ── SECTION 11: Master Summary ────────────────────────────────────────────
    story.append(ColorBox('11.  MASTER SUMMARY — ATP Yield & Quick Reference', C_DARK_BLUE))
    story.append(sp(6))

    story.append(Paragraph('Complete ATP Yield from 1 Glucose Molecule (Aerobic Oxidation)', H2))
    atp_data = [
        ['Stage', 'Process', 'Direct ATP', 'NADH/FADH₂', 'ATP from ETC', 'Total'],
        ['Glycolysis', 'Glucose → 2 Pyruvate (cytosol)', '2', '2 NADH', '5 (M-A shuttle)', '7'],
        ['Pyruvate → Acetyl-CoA', 'PDC (mitochondria)', '0', '2 NADH', '5', '5'],
        ['TCA Cycle ×2', '2 Acetyl-CoA', '2 GTP', '6 NADH + 2 FADH₂', '15 + 3 = 18', '20'],
        ['', 'GRAND TOTAL', '', '', '', '≈ 30–32 ATP'],
    ]
    story.append(make_table(atp_data, col_widths=[W*0.20, W*0.26, W*0.12, W*0.16, W*0.14, W*0.12]))
    story.append(sp(8))

    story.append(Paragraph('Key Regulatory Enzymes — Quick Reference', H2))
    reg_data = [
        ['Enzyme', 'Pathway', 'Activated by', 'Inhibited by'],
        ['Hexokinase', 'Glycolysis', 'Glucose', 'G6P (product inhibition)'],
        ['Glucokinase', 'Glycolysis (liver)', 'Glucose (high Km)', 'No product inhibition'],
        ['PFK-1 ★', 'Glycolysis (rate-limiting)', 'AMP, ADP, F-2,6-BP, insulin', 'ATP, citrate, glucagon'],
        ['Pyruvate Kinase', 'Glycolysis', 'F-1,6-BP (feedforward)', 'ATP, alanine, glucagon'],
        ['Pyruvate Dehydrogenase', 'Pyr → Acetyl-CoA', 'ADP, CoA, NAD+, Ca²+', 'ATP, Acetyl-CoA, NADH'],
        ['Citrate Synthase', 'TCA (entry)', 'OAA, Acetyl-CoA', 'ATP, NADH, succinyl-CoA'],
        ['Isocitrate DH ★', 'TCA (rate-limiting)', 'ADP, Ca²+', 'ATP, NADH'],
        ['G6P Dehydrogenase ★', 'HMP Shunt (rate-limiting)', 'NADP+', 'NADPH (product inhibition)'],
        ['Pyruvate Carboxylase', 'Gluconeogenesis', 'Acetyl-CoA (allosteric)', 'ADP'],
        ['FBPase-1', 'Gluconeogenesis', 'Citrate', 'AMP, F-2,6-BP'],
        ['Glycogen Synthase', 'Glycogenesis', 'G6P, insulin (PP)', 'PKA phosphorylation (glucagon)'],
        ['Glycogen Phosphorylase', 'Glycogenolysis', 'AMP, Ca²+, PKA (glucagon)', 'G6P, ATP, insulin'],
    ]
    story.append(make_table(reg_data, col_widths=[W*0.22, W*0.18, W*0.30, W*0.30]))
    story.append(sp(8))

    story.append(Paragraph('Clinically Important Metabolic Diseases', H2))
    clin_data = [
        ['Disease', 'Defect', 'Key Features'],
        ['G6PD Deficiency', 'G6P Dehydrogenase (HMP shunt)', 'Episodic hemolytic anemia; triggered by oxidants; X-linked; Heinz bodies'],
        ['Galactosaemia', 'Galactose-1-P uridyltransferase (Type 1)', 'Neonatal jaundice, cataracts, liver failure; reducing sugar in urine'],
        ['Fructose Intolerance', 'Aldolase B (liver)', 'Hypoglycemia after fructose; liver damage; avoid sucrose/sorbitol'],
        ['Von Gierke Disease (GSD Ia)', 'Glucose-6-Phosphatase', 'Fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperlipidemia'],
        ['McArdle Disease (GSD V)', 'Muscle Glycogen Phosphorylase', 'Exercise intolerance, cramps, myoglobinuria; no rise in lactate on exercise'],
        ['Pyruvate Kinase Deficiency', 'Pyruvate Kinase (RBCs)', 'Chronic hemolytic anemia; ↑ 2,3-BPG (right-shift of O₂ curve)'],
        ['Hurler Syndrome', 'α-L-Iduronidase (GAG degradation)', 'Coarse facies, corneal clouding, organomegaly, intellectual disability'],
    ]
    story.append(make_table(clin_data, col_widths=[W*0.25, W*0.28, W*0.47]))
    story.append(sp(8))

    story.append(Paragraph('All Mnemonics — Quick Recall', H2))
    mn_data = [
        ['Topic', 'Mnemonic'],
        ['Glycolysis 10 steps', '"Goodness Gracious, Father Franklin Did Go By Picking Peas"\nGlucose → G6P → F6P → F1,6BP → DHAP/G3P → 1,3BPG → 3PG → 2PG → PEP → Pyruvate'],
        ['TCA cycle intermediates', '"Citrate Is Krebs\' Starting Substrate For Making OAA"\nCitrate → Isocitrate → α-KG → Succinyl-CoA → Succinate → Fumarate → Malate → OAA'],
        ['Gluconeogenic precursors', '"GOAL" — Glycerol, Odd-chain fatty acids, Amino acids, Lactate'],
        ['Hypoglycemia hormones', '"GECGo" — Glucagon (1st), Epinephrine (2nd), Cortisol (3rd), Growth hormone (4th)'],
        ['Glycolysis regulators', 'PFK-1: "CAFE" activates = Citrate Absent (inhibitor), Fructose-2,6-BP, AMP/ADP, Energy low'],
        ['Glycogenesis vs lysis', '"Synthase Dephosphorylated = Active" (insulin state)\n"Phosphorylase Phosphorylated = Active" (glucagon/epi state)'],
    ]
    story.append(make_table(mn_data, col_widths=[W*0.30, W*0.70],
                            header_bg=C_PURPLE, alt_bg=C_PURPLE_LIGHT))
    story.append(sp(6))
    story.append(Paragraph('Sources: Basic Medical Biochemistry - A Clinical Approach 6e  |  Guyton and Hall Textbook of Medical Physiology  |  Tietz Textbook of Laboratory Medicine 7e  |  Goodman & Gilman\'s Pharmacological Basis of Therapeutics', CAPTION))

    doc.build(story)
    print(f"PDF created: {path}")
    return path

if __name__ == '__main__':
    build()

cd /home/daytona/workspace/carb-studyguide && python generate_pdf.py 2>&1

~/carb-studyguide/generate_pdf.py

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/carb-studyguide/generate_pdf.py'

~/carb-studyguide/generate_pdf.py

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/carb-studyguide/generate_pdf.py'

~/carb-studyguide/generate_pdf.py

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/carb-studyguide/generate_pdf.py'

cd /home/daytona/workspace/carb-studyguide && python generate_pdf.py 2>&1

ls -lh /home/daytona/workspace/carb-studyguide/Carbohydrates_Glucose_Metabolism_…

~/nucleic-acids-guide/generate_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.lib.colors import HexColor, white, black
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus.flowables import Flowable
import math, os

os.makedirs('/home/daytona/workspace/nucleic-acids-guide', exist_ok=True)

# ── Colors ────────────────────────────────────────────────────────────────────
C_NAVY        = HexColor('#0f2d5e')
C_BLUE        = HexColor('#1d4ed8')
C_BLUE_LIGHT  = HexColor('#dbeafe')
C_TEAL        = HexColor('#0d9488')
C_TEAL_LIGHT  = HexColor('#ccfbf1')
C_RED         = HexColor('#dc2626')
C_RED_LIGHT   = HexColor('#fee2e2')
C_PURPLE      = HexColor('#7c3aed')
C_PURPLE_LIGHT= HexColor('#ede9fe')
C_ORANGE      = HexColor('#ea580c')
C_ORANGE_LIGHT= HexColor('#fff7ed')
C_GREEN       = HexColor('#16a34a')
C_GREEN_LIGHT = HexColor('#dcfce7')
C_GOLD        = HexColor('#b45309')
C_GOLD_LIGHT  = HexColor('#fef3c7')
C_GRAY        = HexColor('#64748b')
C_GRAY_DARK   = HexColor('#1e293b')
C_GRAY_LIGHT  = HexColor('#f1f5f9')

PAGE_W = A4[0]
PAGE_H = A4[1]
W = PAGE_W - 2*cm

# ── Styles ────────────────────────────────────────────────────────────────────
def S(name, **kw): return ParagraphStyle(name, **kw)

H1  = S('H1',  fontSize=13, fontName='Helvetica-Bold', textColor=white,
        spaceBefore=2, spaceAfter=4)
H2  = S('H2',  fontSize=11.5, fontName='Helvetica-Bold', textColor=C_NAVY,
        spaceBefore=10, spaceAfter=4)
H3  = S('H3',  fontSize=10.5, fontName='Helvetica-Bold', textColor=C_BLUE,
        spaceBefore=7, spaceAfter=3)
BODY= S('Body',fontSize=9.5,  fontName='Helvetica', textColor=C_GRAY_DARK,
        leading=14, spaceBefore=2, spaceAfter=2, alignment=TA_JUSTIFY)
BB  = S('BB',  fontSize=9.5,  fontName='Helvetica-Bold', textColor=C_GRAY_DARK,
        leading=14, spaceBefore=2, spaceAfter=2)
BUL = S('Bul', fontSize=9.5,  fontName='Helvetica', textColor=C_GRAY_DARK,
        leading=14, spaceBefore=1, spaceAfter=1, leftIndent=14, bulletIndent=4)
BU2 = S('Bu2', fontSize=9,    fontName='Helvetica', textColor=C_GRAY_DARK,
        leading=13, spaceBefore=1, spaceAfter=1, leftIndent=28, bulletIndent=18)
CAP = S('Cap', fontSize=8,    fontName='Helvetica-Oblique', textColor=C_GRAY,
        alignment=TA_CENTER, spaceBefore=2, spaceAfter=4)
MNE = S('Mne', fontSize=9.5,  fontName='Helvetica-Bold', textColor=C_PURPLE,
        leading=14, spaceBefore=2, spaceAfter=2, leftIndent=10)

def sp(h=4): return Spacer(1, h)
def hr(c=C_BLUE_LIGHT): return HRFlowable(width='100%', thickness=1, color=c, spaceAfter=4, spaceBefore=4)

# ── Section Header ─────────────────────────────────────────────────────────────
class SectionHeader(Flowable):
    def __init__(self, text, bg, icon='', height=30, fontsize=13):
        Flowable.__init__(self)
        self.text = text; self.bg = bg; self.icon = icon
        self.height = height; self.fontsize = fontsize
    def wrap(self, *a): return (W, self.height + 6)
    def draw(self):
        c = self.canv
        c.setFillColor(self.bg)
        c.roundRect(0, 0, W, self.height, 6, fill=1, stroke=0)
        c.setFillColor(white)
        c.setFont('Helvetica-Bold', self.fontsize)
        c.drawString(12, 9, self.text)

# ── Info box ─────────────────────────────────────────────────────────────────
class InfoBox(Flowable):
    def __init__(self, lines, bg, border, label=''):
        Flowable.__init__(self)
        self.lines=lines; self.bg=bg; self.border=border; self.label=label
    def wrap(self, aw, ah):
        lh = 13
        label_h = lh if self.label else 0
        self.height = lh * len(self.lines) + label_h + 14
        return (W, self.height)
    def draw(self):
        c = self.canv
        h = self.height
        c.setFillColor(self.bg)
        c.roundRect(0, 0, W, h, 5, fill=1, stroke=0)
        c.setStrokeColor(self.border); c.setLineWidth(1.5)
        c.roundRect(0, 0, W, h, 5, fill=0, stroke=1)
        c.setFillColor(self.border)
        off = 0
        if self.label:
            c.setFont('Helvetica-Bold', 9)
            c.drawString(10, h-14, self.label)
            off = 13
        c.setFont('Helvetica', 9); c.setFillColor(C_GRAY_DARK)
        for i, ln in enumerate(self.lines):
            y = h - 14 - off - 13*i
            if ln.startswith('**') and ln.endswith('**'):
                c.setFont('Helvetica-Bold', 9)
                c.drawString(12, y, ln.strip('*'))
                c.setFont('Helvetica', 9)
            else:
                c.drawString(12, y, ln)

# ── tRNA Cloverleaf Drawing ───────────────────────────────────────────────────
class TRNACloverleaf(Flowable):
    """Hand-drawn tRNA cloverleaf structure using ReportLab canvas."""
    def __init__(self, width=500, height=480):
        Flowable.__init__(self)
        self._w = width; self._h = height
    def wrap(self, *a): return (self._w, self._h)

    def _stem(self, c, cx, cy, angle_deg, length, pairs, color, label='', label_side='right'):
        """Draw a stem as a series of base pair rungs."""
        angle = math.radians(angle_deg)
        rung_spacing = 14
        rung_half = 10
        perp = math.radians(angle_deg + 90)
        c.setStrokeColor(color); c.setLineWidth(1.8)
        for i in range(pairs):
            # backbone strand 1
            x1 = cx + math.cos(angle) * i * rung_spacing - math.cos(perp) * rung_half
            y1 = cy + math.sin(angle) * i * rung_spacing - math.sin(perp) * rung_half
            x2 = cx + math.cos(angle) * i * rung_spacing + math.cos(perp) * rung_half
            y2 = cy + math.sin(angle) * i * rung_spacing + math.sin(perp) * rung_half
            c.line(x1, y1, x2, y2)
        # backbone lines
        c.setLineWidth(2.5)
        x_start1 = cx - math.cos(perp) * rung_half
        y_start1 = cy - math.sin(perp) * rung_half
        x_end1   = cx + math.cos(angle) * (pairs-1) * rung_spacing - math.cos(perp) * rung_half
        y_end1   = cy + math.sin(angle) * (pairs-1) * rung_spacing - math.sin(perp) * rung_half
        c.line(x_start1, y_start1, x_end1, y_end1)
        x_start2 = cx + math.cos(perp) * rung_half
        y_start2 = cy + math.sin(perp) * rung_half
        x_end2   = cx + math.cos(angle) * (pairs-1) * rung_spacing + math.cos(perp) * rung_half
        y_end2   = cy + math.sin(angle) * (pairs-1) * rung_spacing + math.sin(perp) * rung_half
        c.line(x_start2, y_start2, x_end2, y_end2)

    def _loop(self, c, cx, cy, radius, color, label, label_color, nucleotides=7, fill=None):
        """Draw a loop circle with label."""
        c.setStrokeColor(color); c.setLineWidth(2)
        if fill:
            c.setFillColor(fill)
            c.circle(cx, cy, radius, fill=1, stroke=1)
        else:
            c.circle(cx, cy, radius, fill=0, stroke=1)
        c.setFillColor(label_color); c.setFont('Helvetica-Bold', 9)
        c.drawCentredString(cx, cy - 4, label)

    def draw(self):
        c = self.canv
        W_d, H_d = self._w, self._h

        # Background
        c.setFillColor(HexColor('#f8fafc'))
        c.roundRect(0, 0, W_d, H_d, 10, fill=1, stroke=0)
        c.setStrokeColor(HexColor('#cbd5e1')); c.setLineWidth(1)
        c.roundRect(0, 0, W_d, H_d, 10, fill=0, stroke=1)

        # Title
        c.setFillColor(C_NAVY); c.setFont('Helvetica-Bold', 13)
        c.drawCentredString(W_d/2, H_d - 24, 'tRNA Cloverleaf Structure')
        c.setFont('Helvetica', 8.5); c.setFillColor(C_GRAY)
        c.drawCentredString(W_d/2, H_d - 38, '(2D Cloverleaf → folds into 3D L-shaped tertiary structure)')

        # ── Central coordinate system ─────────────────────────────────────────
        # Center of the molecule junction area
        cx = W_d / 2
        # We'll place: Acceptor stem (top), D-loop (upper left), Anticodon loop (bottom),
        # TψC loop (upper right), Variable loop (right)

        # ── ACCEPTOR STEM (top, vertical) ─────────────────────────────────────
        acc_base_x = cx
        acc_base_y = 280
        stem_bp = 7
        rung_sp = 14
        rung_h  = 12

        c.setLineWidth(2.5)
        # Left backbone (5' end)
        c.setStrokeColor(C_NAVY)
        c.line(acc_base_x - rung_h, acc_base_y, acc_base_x - rung_h, acc_base_y + stem_bp * rung_sp)
        # Right backbone (3' end)
        c.setStrokeColor(C_RED)
        c.line(acc_base_x + rung_h, acc_base_y, acc_base_x + rung_h, acc_base_y + stem_bp * rung_sp)
        # Base pair rungs
        c.setStrokeColor(HexColor('#64748b')); c.setLineWidth(1.5)
        for i in range(stem_bp):
            y = acc_base_y + i * rung_sp
            c.line(acc_base_x - rung_h, y, acc_base_x + rung_h, y)

        # 5' and 3' labels
        c.setFillColor(C_NAVY); c.setFont('Helvetica-Bold', 10)
        c.drawRightString(acc_base_x - rung_h - 3, acc_base_y + stem_bp * rung_sp + 4, "5'")
        c.setFillColor(C_RED)
        c.drawString(acc_base_x + rung_h + 3, acc_base_y + stem_bp * rung_sp + 4, "3' -CCA")

        # Acceptor stem label
        c.setFillColor(C_NAVY); c.setFont('Helvetica-Bold', 8.5)
        c.drawCentredString(acc_base_x + 52, acc_base_y + 50, 'ACCEPTOR STEM')
        c.setFillColor(C_GRAY); c.setFont('Helvetica', 7.5)
        c.drawCentredString(acc_base_x + 52, acc_base_y + 40, '(7 base pairs)')
        c.drawCentredString(acc_base_x + 52, acc_base_y + 30, 'Amino acid attaches')
        c.drawCentredString(acc_base_x + 52, acc_base_y + 20, "at 3' CCA-OH end")

        # ── D-LOOP (upper left) ───────────────────────────────────────────────
        # Stem going down-left from acceptor
        dl_stem_start_x = acc_base_x - rung_h
        dl_stem_start_y = acc_base_y

        # D-loop stem (3-4 bp going left-down)
        d_stem_pairs = 4
        d_stem_angle = -135  # degrees
        da = math.radians(d_stem_angle)
        perp_da = math.radians(d_stem_angle + 90)
        rh = 8

        c.setLineWidth(2.5); c.setStrokeColor(C_NAVY)
        for i in range(d_stem_pairs):
            bx = dl_stem_start_x + math.cos(da) * i * rung_sp
            by = dl_stem_start_y + math.sin(da) * i * rung_sp
            x1 = bx - math.cos(perp_da) * rh
            y1 = by - math.sin(perp_da) * rh
            x2 = bx + math.cos(perp_da) * rh
            y2 = by + math.sin(perp_da) * rh
            c.setStrokeColor(HexColor('#64748b')); c.setLineWidth(1.5)
            c.line(x1, y1, x2, y2)

        # D-loop backbones
        c.setLineWidth(2.5); c.setStrokeColor(C_NAVY)
        c.line(dl_stem_start_x,
               dl_stem_start_y,
               dl_stem_start_x + math.cos(da) * (d_stem_pairs-1) * rung_sp - math.cos(perp_da)*rh,
               dl_stem_start_y + math.sin(da) * (d_stem_pairs-1) * rung_sp - math.sin(perp_da)*rh)

        d_loop_cx = dl_stem_start_x + math.cos(da) * d_stem_pairs * rung_sp
        d_loop_cy = dl_stem_start_y + math.sin(da) * d_stem_pairs * rung_sp

        # D loop circle
        d_r = 28
        c.setFillColor(C_GOLD_LIGHT); c.setStrokeColor(C_GOLD); c.setLineWidth(2)
        c.circle(d_loop_cx, d_loop_cy, d_r, fill=1, stroke=1)
        c.setFillColor(C_GOLD); c.setFont('Helvetica-Bold', 9)
        c.drawCentredString(d_loop_cx, d_loop_cy + 3, 'D-LOOP')
        c.setFont('Helvetica', 7.5)
        c.drawCentredString(d_loop_cx, d_loop_cy - 9, '(DiHydroUridine)')

        # D-loop arm label
        c.setFillColor(C_GOLD); c.setFont('Helvetica-Bold', 8.5)
        c.drawCentredString(d_loop_cx - 48, d_loop_cy + 14, 'D-ARM')
        c.setFillColor(C_GRAY); c.setFont('Helvetica', 7.5)
        c.drawCentredString(d_loop_cx - 48, d_loop_cy + 4, '(3-4 bp stem)')

        # ── TψC LOOP (upper right) ────────────────────────────────────────────
        tc_stem_start_x = acc_base_x + rung_h
        tc_stem_start_y = acc_base_y
        tc_angle = -45
        tc_a = math.radians(tc_angle)
        perp_tc = math.radians(tc_angle + 90)
        tc_pairs = 5

        c.setStrokeColor(C_TEAL)
        for i in range(tc_pairs):
            bx = tc_stem_start_x + math.cos(tc_a) * i * rung_sp
            by = tc_stem_start_y + math.sin(tc_a) * i * rung_sp
            x1 = bx - math.cos(perp_tc) * rh
            y1 = by - math.sin(perp_tc) * rh
            x2 = bx + math.cos(perp_tc) * rh
            y2 = by + math.sin(perp_tc) * rh
            c.setStrokeColor(HexColor('#64748b')); c.setLineWidth(1.5)
            c.line(x1, y1, x2, y2)

        c.setLineWidth(2.5); c.setStrokeColor(C_TEAL)
        c.line(tc_stem_start_x, tc_stem_start_y,
               tc_stem_start_x + math.cos(tc_a) * (tc_pairs-1) * rung_sp + math.cos(perp_tc)*rh,
               tc_stem_start_y + math.sin(tc_a) * (tc_pairs-1) * rung_sp + math.sin(perp_tc)*rh)

        tc_loop_cx = tc_stem_start_x + math.cos(tc_a) * tc_pairs * rung_sp
        tc_loop_cy = tc_stem_start_y + math.sin(tc_a) * tc_pairs * rung_sp

        tc_r = 28
        c.setFillColor(C_TEAL_LIGHT); c.setStrokeColor(C_TEAL); c.setLineWidth(2)
        c.circle(tc_loop_cx, tc_loop_cy, tc_r, fill=1, stroke=1)
        c.setFillColor(C_TEAL); c.setFont('Helvetica-Bold', 8.5)
        c.drawCentredString(tc_loop_cx, tc_loop_cy + 5, 'TψC-LOOP')
        c.setFont('Helvetica', 7.5)
        c.drawCentredString(tc_loop_cx, tc_loop_cy - 7, '(RiboThymidine +')
        c.drawCentredString(tc_loop_cx, tc_loop_cy - 17, 'Pseudouridine)')

        # TψC arm label
        c.setFillColor(C_TEAL); c.setFont('Helvetica-Bold', 8.5)
        c.drawString(tc_loop_cx + 38, tc_loop_cy + 14, 'TψC-ARM')
        c.setFillColor(C_GRAY); c.setFont('Helvetica', 7.5)
        c.drawString(tc_loop_cx + 38, tc_loop_cy + 4, '(5 bp stem)')

        # ── VARIABLE LOOP (right middle) ─────────────────────────────────────
        var_cx = tc_loop_cx + 2
        var_cy = 215
        c.setStrokeColor(C_TEAL); c.setLineWidth(1.5)
        c.line(tc_loop_cx, tc_loop_cy - tc_r, var_cx, var_cy + 16)
        c.setFillColor(C_GRAY_LIGHT); c.setStrokeColor(C_ORANGE); c.setLineWidth(2)
        c.ellipse(var_cx - 22, var_cy - 12, var_cx + 22, var_cy + 12, fill=1, stroke=1)
        c.setFillColor(C_ORANGE); c.setFont('Helvetica-Bold', 8)
        c.drawCentredString(var_cx, var_cy + 1, 'VARIABLE LOOP')
        c.setFillColor(C_GRAY); c.setFont('Helvetica', 7)
        c.drawString(var_cx + 26, var_cy + 1, '(varies 4-21 nt)')

        # ── ANTICODON STEM + LOOP (bottom) ────────────────────────────────────
        # Stem going straight down from junction
        ac_stem_start_x = cx
        ac_stem_start_y = acc_base_y - 4
        ac_pairs = 5

        # Left backbone
        c.setLineWidth(2.5); c.setStrokeColor(C_NAVY)
        c.line(acc_base_x - rung_h, acc_base_y - 2,
               acc_base_x - rung_h, acc_base_y - ac_pairs * rung_sp - 2)
        # Right backbone
        c.setStrokeColor(HexColor('#475569'))
        c.line(acc_base_x + rung_h, acc_base_y - 2,
               acc_base_x + rung_h, acc_base_y - ac_pairs * rung_sp - 2)

        # Anticodon stem rungs
        c.setStrokeColor(HexColor('#64748b')); c.setLineWidth(1.5)
        for i in range(1, ac_pairs + 1):
            y = acc_base_y - i * rung_sp
            c.line(acc_base_x - rung_h, y, acc_base_x + rung_h, y)

        # Anticodon loop
        ac_loop_cx = acc_base_x
        ac_loop_cy = acc_base_y - ac_pairs * rung_sp - 35
        ac_r = 36

        c.setFillColor(C_RED_LIGHT); c.setStrokeColor(C_RED); c.setLineWidth(2.5)
        c.circle(ac_loop_cx, ac_loop_cy, ac_r, fill=1, stroke=1)
        c.setFillColor(C_RED); c.setFont('Helvetica-Bold', 9.5)
        c.drawCentredString(ac_loop_cx, ac_loop_cy + 12, 'ANTICODON')
        c.drawCentredString(ac_loop_cx, ac_loop_cy - 1, 'LOOP')
        c.setFont('Helvetica-Bold', 8)
        c.setFillColor(C_NAVY)
        c.drawCentredString(ac_loop_cx, ac_loop_cy - 14, "(5'- N-N-N -3')")

        # Connect stem bottoms to anticodon loop
        c.setStrokeColor(C_NAVY); c.setLineWidth(2.5)
        c.line(acc_base_x - rung_h, acc_base_y - ac_pairs * rung_sp,
               ac_loop_cx - rung_h, ac_loop_cy + ac_r)
        c.setStrokeColor(HexColor('#475569'))
        c.line(acc_base_x + rung_h, acc_base_y - ac_pairs * rung_sp,
               ac_loop_cx + rung_h, ac_loop_cy + ac_r)

        # Anticodon arm label
        c.setFillColor(C_RED); c.setFont('Helvetica-Bold', 8.5)
        c.drawRightString(ac_loop_cx - 50, ac_loop_cy + 10, 'ANTICODON ARM')
        c.setFillColor(C_GRAY); c.setFont('Helvetica', 7.5)
        c.drawRightString(ac_loop_cx - 50, ac_loop_cy, '(5 bp stem)')
        c.drawRightString(ac_loop_cx - 50, ac_loop_cy - 10, 'Pairs with mRNA codon')

        # ── JUNCTION connecting D-loop stem end to anticodon stem ──────────────
        # Connect D-loop return to anticodon stem left
        d_return_x = dl_stem_start_x + math.cos(da) * (d_stem_pairs-1) * rung_sp - math.cos(perp_da)*rh
        d_return_y = dl_stem_start_y + math.sin(da) * (d_stem_pairs-1) * rung_sp - math.sin(perp_da)*rh
        c.setStrokeColor(C_NAVY); c.setLineWidth(2)
        c.line(d_return_x, d_return_y, acc_base_x - rung_h, acc_base_y)

        # ── LEGEND ───────────────────────────────────────────────────────────
        leg_x = 15; leg_y = 100
        c.setFillColor(C_NAVY); c.setFont('Helvetica-Bold', 9)
        c.drawString(leg_x, leg_y + 60, 'LEGEND:')

        items = [
            (C_NAVY,        "5' end strand"),
            (C_RED,         "3' end strand (—CCA—OH)"),
            (C_GOLD,        "D-loop (Dihydrouridine)"),
            (C_RED,         "Anticodon loop"),
            (C_TEAL,        "TψC loop"),
            (C_ORANGE,      "Variable loop"),
        ]
        for i, (col, txt) in enumerate(items):
            y = leg_y + 44 - i * 13
            c.setFillColor(col)
            c.rect(leg_x, y+1, 12, 8, fill=1, stroke=0)
            c.setFillColor(C_GRAY_DARK); c.setFont('Helvetica', 8)
            c.drawString(leg_x + 16, y + 1, txt)

        # ── Key facts box ─────────────────────────────────────────────────────
        bx, by = 300, 32
        c.setFillColor(C_BLUE_LIGHT); c.setStrokeColor(C_BLUE)
        c.roundRect(bx, by, W_d - bx - 10, 80, 5, fill=1, stroke=1)
        c.setFillColor(C_NAVY); c.setFont('Helvetica-Bold', 8.5)
        c.drawString(bx + 8, by + 62, 'Key Facts:')
        facts = [
            '• ~73-93 nucleotides long',
            '• Contains modified bases (D, T, ψ)',
            "• 3'-CCA is universal amino acid attachment",
            '• Anticodon (3 nt) pairs with mRNA codon',
            '• Folds into L-shaped 3D tertiary structure',
        ]
        c.setFillColor(C_GRAY_DARK); c.setFont('Helvetica', 7.5)
        for i, f in enumerate(facts):
            c.drawString(bx + 8, by + 50 - i * 11, f)


# ── Table Helper ─────────────────────────────────────────────────────────────
def make_table(data, cw=None, hbg=None, alt=None):
    hbg = hbg or C_NAVY; alt = alt or HexColor('#eff6ff')
    ts = TableStyle([
        ('BACKGROUND',    (0,0), (-1,0), hbg),
        ('TEXTCOLOR',     (0,0), (-1,0), white),
        ('FONTNAME',      (0,0), (-1,0), 'Helvetica-Bold'),
        ('FONTSIZE',      (0,0), (-1,0), 9),
        ('FONTNAME',      (0,1), (-1,-1), 'Helvetica'),
        ('FONTSIZE',      (0,1), (-1,-1), 8.5),
        ('TEXTCOLOR',     (0,1), (-1,-1), C_GRAY_DARK),
        ('ROWBACKGROUNDS',(0,1), (-1,-1), [white, alt]),
        ('GRID',          (0,0), (-1,-1), 0.5, HexColor('#cbd5e1')),
        ('VALIGN',        (0,0), (-1,-1), 'MIDDLE'),
        ('LEFTPADDING',   (0,0), (-1,-1), 6),
        ('RIGHTPADDING',  (0,0), (-1,-1), 6),
        ('TOPPADDING',    (0,0), (-1,-1), 4),
        ('BOTTOMPADDING', (0,0), (-1,-1), 4),
    ])
    t = Table(data, colWidths=cw, repeatRows=1)
    t.setStyle(ts)
    return t

# ── Canvas callbacks ──────────────────────────────────────────────────────────
def draw_cover(canvas, doc):
    w, h = A4
    canvas.saveState()
    canvas.setFillColor(C_NAVY)
    canvas.rect(0, 0, w, h, fill=1, stroke=0)
    canvas.setFillColor(HexColor('#1d3a6e'))
    canvas.rect(0, h*0.36, w, h*0.28, fill=1, stroke=0)
    canvas.setFillColor(HexColor('#1e3a80'))
    canvas.circle(w*0.82, h*0.82, 100, fill=1, stroke=0)
    canvas.circle(w*0.12, h*0.13, 70, fill=1, stroke=0)
    canvas.setFillColor(white)
    canvas.setFont('Helvetica-Bold', 36)
    canvas.drawCentredString(w/2, h*0.64, 'NUCLEIC ACIDS')
    canvas.setFont('Helvetica-Bold', 22)
    canvas.setFillColor(HexColor('#bfdbfe'))
    canvas.drawCentredString(w/2, h*0.57, 'DNA  &  RNA')
    canvas.setFont('Helvetica', 14)
    canvas.setFillColor(HexColor('#93c5fd'))
    canvas.drawCentredString(w/2, h*0.51, 'Complete Study Guide')
    canvas.setStrokeColor(HexColor('#e63946'))
    canvas.setLineWidth(3)
    canvas.line(w*0.2, h*0.475, w*0.8, h*0.475)
    canvas.setFont('Helvetica-Bold', 10.5)
    canvas.setFillColor(white)
    topics = [
        '• Structure and Components of DNA',
        '• Functions of DNA',
        '• Types and Functions of RNA',
        '• Differences Between DNA and RNA',
        '• Structure and Function of tRNA',
        '• Cloverleaf Structure of tRNA (Detailed Diagram)',
        '• Modified Bases in RNA',
        '• Clinical Correlations',
    ]
    y = h*0.44
    for t in topics:
        canvas.drawCentredString(w/2, y, t)
        y -= 20
    canvas.setFont('Helvetica', 8.5)
    canvas.setFillColor(HexColor('#94a3b8'))
    canvas.drawCentredString(w/2, 28, 'Sources: Thompson & Thompson Genetics 9e  |  Basic Medical Biochemistry 6e  |  Harper\'s Illustrated Biochemistry 32e')
    canvas.restoreState()

def draw_later(canvas, doc):
    w, h = A4
    canvas.saveState()
    canvas.setFillColor(C_NAVY)
    canvas.rect(0, h-22, w, 22, fill=1, stroke=0)
    canvas.setFillColor(white)
    canvas.setFont('Helvetica-Bold', 8)
    canvas.drawString(10, h-15, 'NUCLEIC ACIDS — DNA & RNA  |  Study Guide')
    canvas.setFont('Helvetica', 8)
    canvas.drawRightString(w-10, h-15, f'Page {doc.page}')
    canvas.setFillColor(C_GRAY)
    canvas.setFont('Helvetica', 7.5)
    canvas.drawCentredString(w/2, 14, 'Thompson & Thompson Genetics 9e  |  Basic Medical Biochemistry 6e  |  Harper\'s Illustrated Biochemistry 32e')
    canvas.restoreState()

# ── Build ─────────────────────────────────────────────────────────────────────
def build():
    out = '/home/daytona/workspace/nucleic-acids-guide/Nucleic_Acids_DNA_RNA_StudyGuide.pdf'
    doc = SimpleDocTemplate(out, pagesize=A4,
        leftMargin=1*cm, rightMargin=1*cm,
        topMargin=1.5*cm, bottomMargin=1.2*cm,
        title='Nucleic Acids – DNA & RNA Study Guide')
    story = []
    story.append(PageBreak())  # cover on page 1

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 1: NUCLEIC ACIDS — OVERVIEW
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('1.  NUCLEIC ACIDS — Overview & Components', C_NAVY))
    story.append(sp(6))
    story.append(Paragraph(
        'Nucleic acids are biological macromolecules that store and transmit genetic information and direct protein synthesis. '
        'There are two types: <b>DNA (Deoxyribonucleic Acid)</b> and <b>RNA (Ribonucleic Acid)</b>.',
        BODY))
    story.append(sp(6))

    story.append(Paragraph('Building Blocks — Nucleotides', H2))
    story.append(Paragraph(
        'A <b>nucleotide</b> = three components joined together:', BODY))
    comps = [
        '1. <b>Pentose sugar</b> — Deoxyribose (DNA) or Ribose (RNA)',
        '2. <b>Nitrogenous base</b> — Purine or Pyrimidine',
        '3. <b>Phosphate group</b> — One or more phosphates (mono/di/triphosphate)',
    ]
    for c in comps:
        story.append(Paragraph(c, BUL))
    story.append(sp(6))

    story.append(Paragraph(
        'A <b>nucleoside</b> = sugar + base only (no phosphate). '
        'Nucleotides are linked by <b>3\'–5\' phosphodiester bonds</b> forming long polynucleotide chains.', BODY))
    story.append(sp(6))

    story.append(Paragraph('Nitrogenous Bases', H2))
    base_data = [
        ['Type', 'Base', 'Found in', 'Structure', 'Pairs with'],
        ['Purine\n(double ring)', 'Adenine (A)', 'DNA & RNA', '6-aminopurine', 'T (DNA) or U (RNA)'],
        ['Purine\n(double ring)', 'Guanine (G)', 'DNA & RNA', '2-amino-6-oxopurine', 'C (DNA & RNA)'],
        ['Pyrimidine\n(single ring)', 'Cytosine (C)', 'DNA & RNA', '2-oxo-4-aminopyrimidine', 'G (DNA & RNA)'],
        ['Pyrimidine\n(single ring)', 'Thymine (T)', 'DNA ONLY', '2,4-dioxo-5-methylpyrimidine', 'A (DNA)'],
        ['Pyrimidine\n(single ring)', 'Uracil (U)', 'RNA ONLY', '2,4-dioxopyrimidine (no methyl)', 'A (RNA)'],
    ]
    story.append(make_table(base_data, cw=[W*0.18, W*0.12, W*0.14, W*0.30, W*0.14]))
    story.append(sp(4))
    story.append(InfoBox(
        ['★  Mnemonic — Purines (double ring): "PURe As Gold" = PURines: Adenine, Guanine',
         '   Pyrimidines (single ring): "CUT the PY" = Cytosine, Uracil, Thymine are PYrimidines',
         '   "Funny (Phunny) = Pyrimidines" — C, U, T are "funny" (single ring)'],
        C_PURPLE_LIGHT, C_PURPLE, ''))
    story.append(sp(6))

    story.append(Paragraph('Watson-Crick Base Pairing Rules', H3))
    story.append(Paragraph('<b>A=T</b> (2 hydrogen bonds) | <b>G≡C</b> (3 hydrogen bonds, stronger!)', BB))
    story.append(Paragraph(
        'Because G≡C pairs have 3 H-bonds, DNA with high G+C content has a higher melting temperature (Tm). '
        'This is used in molecular biology to estimate DNA stability.', BODY))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 2: DNA — STRUCTURE
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('2.  DNA — Structure', C_BLUE))
    story.append(sp(6))

    story.append(Paragraph('The Watson-Crick Double Helix Model (1953)', H2))
    story.append(Paragraph(
        'DNA exists as a <b>right-handed double helix</b>, as proposed by James Watson and Francis Crick in 1953 '
        '(based on X-ray crystallography data by Rosalind Franklin and Maurice Wilkins). '
        'It resembles a twisted ladder (spiral staircase).', BODY))
    story.append(sp(4))

    dna_feat = [
        ['Feature', 'Detail'],
        ['Two strands', 'Two antiparallel polynucleotide chains (one runs 5\'→3\', the other 3\'→5\')'],
        ['Antiparallel orientation', '5\' end of one strand faces the 3\' end of the other'],
        ['Backbone', 'Sugar-phosphate backbone on the outside of the helix'],
        ['Bases', 'Nitrogenous bases face the inside, stacked perpendicular to helix axis'],
        ['Helix direction', 'Right-handed (B-form is most common in cells)'],
        ['Helix diameter', '~2 nm (20 Å)'],
        ['Base pairs per turn', '10 bp per turn (B-DNA)'],
        ['Rise per base pair', '0.34 nm (3.4 Å)'],
        ['Pitch (full turn)', '3.4 nm per complete turn'],
        ['H-bonds', 'A=T (2 H-bonds); G≡C (3 H-bonds)'],
        ['Major groove', 'Wide groove — accessible to most regulatory proteins and restriction enzymes'],
        ['Minor groove', 'Narrow groove — some drugs and proteins bind here'],
    ]
    story.append(make_table(dna_feat, cw=[W*0.30, W*0.70]))
    story.append(sp(8))

    story.append(Paragraph('Forms of DNA Double Helix', H3))
    forms_data = [
        ['Form', 'Helix', 'bp/turn', 'Conditions', 'Significance'],
        ['B-DNA', 'Right-handed', '10', 'Physiological (aqueous)', 'Most common in living cells (Watson-Crick form)'],
        ['A-DNA', 'Right-handed', '11', 'Dehydrated conditions', 'Seen in RNA-DNA hybrids'],
        ['Z-DNA', 'Left-handed', '12', 'High salt; CG repeats', 'May play a role in gene regulation'],
    ]
    story.append(make_table(forms_data, cw=[W*0.12, W*0.16, W*0.12, W*0.25, W*0.35]))
    story.append(sp(8))

    story.append(Paragraph('DNA Packaging in the Nucleus', H2))
    pack = [
        '• DNA wraps around <b>histone</b> proteins (H2A, H2B, H3, H4 × 2 each) forming the <b>nucleosome</b> (core particle)',
        '• ~147 bp of DNA wraps 1.65 turns around each nucleosome',
        '• Nucleosomes joined by linker DNA (~20-60 bp) + H1 histone = <b>"beads on a string"</b> (10 nm fiber)',
        '• Further coiling → 30 nm fiber (solenoid) → loops → scaffold → chromosome',
        '• Total compaction from ~2 meters of DNA to ~6 μm nucleus!',
    ]
    for p in pack:
        story.append(Paragraph(p, BUL))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 3: DNA — FUNCTIONS
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('3.  DNA — Functions', C_NAVY))
    story.append(sp(6))

    func_data = [
        ['Function', 'Description', 'How'],
        ['1. Genetic Information Storage', 'DNA carries the hereditary blueprint of every organism in the sequence of its bases (A, T, G, C)', 'Linear sequence of codons encodes amino acid sequences of all proteins'],
        ['2. Replication (Self-copying)', 'Exact duplication before cell division; each daughter cell gets an identical copy', 'Semi-conservative: each strand serves as template; DNA Polymerase synthesizes new strand'],
        ['3. Transcription (Gene Expression)', 'DNA serves as template for RNA synthesis', 'RNA Polymerase reads 3\'→5\' template strand; produces mRNA (5\'→3\')'],
        ['4. Mutation & Evolution', 'Base sequence changes (mutations) introduce genetic variation', 'Point mutations, insertions, deletions drive evolution and disease'],
        ['5. Recombination', 'Genetic diversity via chromosomal crossover during meiosis', 'Homologous recombination shuffles alleles between homologous chromosomes'],
        ['6. Regulation', 'Controls when and how much protein is made', 'Promoters, enhancers, silencers are regulatory DNA sequences'],
    ]
    story.append(make_table(func_data, cw=[W*0.28, W*0.38, W*0.34]))
    story.append(sp(8))

    story.append(Paragraph('DNA Replication — Key Points', H2))
    rep = [
        '• <b>Semi-conservative:</b> Each new DNA molecule has one old strand + one new strand',
        '• <b>Bidirectional:</b> Replication forks move outward from origin of replication (ori) in both directions',
        '• <b>DNA Polymerase III</b> (prokaryotes) / <b>DNA Polymerase δ/ε</b> (eukaryotes) adds nucleotides 5\'→3\'',
        '• Requires a <b>primer</b> (short RNA) — DNA Pol cannot initiate de novo',
        '• <b>Leading strand</b> — synthesized continuously toward replication fork',
        '• <b>Lagging strand</b> — synthesized discontinuously as Okazaki fragments (away from fork)',
        '• <b>Proofreading</b> — DNA Pol has 3\'→5\' exonuclease activity to correct errors (error rate ~10⁻⁹)',
    ]
    for r in rep:
        story.append(Paragraph(r, BUL))
    story.append(sp(4))
    story.append(InfoBox(
        ['⚠  Clinical: DNA Repair Defects',
         '   Xeroderma Pigmentosum: defective Nucleotide Excision Repair → UV damage not repaired → skin cancer',
         '   Lynch syndrome (HNPCC): defective Mismatch Repair → colorectal cancer',
         '   BRCA1/2 mutations: defective Homologous Recombination → breast and ovarian cancer'],
        C_RED_LIGHT, C_RED, ''))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 4: RNA — Types & Functions
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('4.  RNA — Types and Functions', C_TEAL))
    story.append(sp(6))
    story.append(Paragraph(
        'RNA (Ribonucleic Acid) is a single-stranded nucleic acid transcribed from DNA. '
        'It serves as the intermediary between the genetic code (DNA) and protein synthesis. '
        'Three major functional types + multiple regulatory RNAs exist.',
        BODY))
    story.append(sp(6))

    story.append(Paragraph('A. Three Major Types of RNA', H2))
    major_data = [
        ['Type', 'Abbrev', '% of total RNA', 'Location', 'Function'],
        ['Messenger RNA', 'mRNA', '~3-5%', 'Nucleus → Cytoplasm', 'Carries genetic message (codons) from DNA to ribosome for translation into protein'],
        ['Ribosomal RNA', 'rRNA', '~80%', 'Cytoplasm (ribosomes)', 'Structural and catalytic component of ribosomes; 23S/16S (prokaryote); 28S/18S/5.8S/5S (eukaryote)'],
        ['Transfer RNA', 'tRNA', '~15%', 'Cytoplasm', 'Adaptor molecule: carries specific amino acid to ribosome; anticodon pairs with mRNA codon'],
    ]
    story.append(make_table(major_data, cw=[W*0.17, W*0.10, W*0.13, W*0.18, W*0.42], hbg=C_TEAL))
    story.append(sp(8))

    story.append(Paragraph('B. Other Regulatory RNA Types', H2))
    other_data = [
        ['Type', 'Abbrev', 'Function'],
        ['Small nuclear RNA', 'snRNA', 'Component of spliceosomes; removes introns from pre-mRNA (RNA splicing)'],
        ['Small nucleolar RNA', 'snoRNA', 'Directs chemical modifications (methylation, pseudouridylation) of rRNA and other RNAs in nucleolus'],
        ['MicroRNA', 'miRNA', 'Single-stranded ~22 nt; post-transcriptional gene silencing by binding 3\'UTR of target mRNA → degradation or translation inhibition'],
        ['Small interfering RNA', 'siRNA', 'Double-stranded ~21 nt; RNA interference (RNAi) — cleaves target mRNA; used as experimental tool and therapeutic'],
        ['Long non-coding RNA', 'lncRNA', 'Regulates gene expression at multiple levels; X-chromosome inactivation (XIST), chromatin remodeling'],
        ['Piwi-interacting RNA', 'piRNA', 'Germ-line specific; protects genome from transposable elements/parasitic DNA'],
        ['Ribozyme', '—', 'RNA with catalytic activity (self-splicing introns, ribonuclease P, ribosome peptidyl transferase activity of 23S rRNA)'],
    ]
    story.append(make_table(other_data, cw=[W*0.22, W*0.10, W*0.68], hbg=C_TEAL))
    story.append(sp(8))

    story.append(Paragraph('C. mRNA Structure (Eukaryotic)', H2))
    mrna_parts = [
        ['Component', 'Description', 'Function'],
        ["5' Cap (7-methylguanosine)", "Added co-transcriptionally at 5' end", 'Protects mRNA from degradation; required for ribosome binding (translation initiation)'],
        ['5\' Untranslated Region (UTR)', '5\' of start codon AUG', 'Regulatory; contains Kozak sequence (ribosome binding in eukaryotes)'],
        ['Open Reading Frame (ORF)', 'AUG (start) → UAA/UAG/UGA (stop)', 'Encodes the protein; read in triplet codons'],
        ['3\' UTR', "3' of stop codon", 'Regulatory; binding site for miRNAs; affects stability and translation'],
        ['3\' Poly-A tail', "Added post-transcriptionally; ~200 A's", 'Protects from degradation; aids nuclear export and translation'],
    ]
    story.append(make_table(mrna_parts, cw=[W*0.26, W*0.26, W*0.48], hbg=C_TEAL))
    story.append(sp(8))

    story.append(Paragraph('D. Ribosomal RNA (rRNA) — Key Facts', H2))
    rrna_data = [
        ['Organism', 'Small Subunit', 'Large Subunit', 'Assembled Ribosome', 'rRNA molecules'],
        ['Prokaryotes (E. coli)', '30S  (16S rRNA)', '50S  (23S + 5S rRNA)', '70S', '3 rRNA + ~55 proteins'],
        ['Eukaryotes (Human)', '40S  (18S rRNA)', '60S  (28S + 5.8S + 5S rRNA)', '80S', '4 rRNA + ~80 proteins'],
        ['Mitochondria (Human)', '28S (12S rRNA)', '39S (16S rRNA)', '55S', 'Resembles prokaryotic ribosomes'],
    ]
    story.append(make_table(rrna_data, cw=[W*0.22, W*0.20, W*0.22, W*0.18, W*0.18], hbg=C_TEAL))
    story.append(sp(4))
    story.append(InfoBox(
        ['★  "Goes (G) together (70S)" — 50S + 30S = 70S ribosome (prokaryote)',
         '   "Eukaryote Eighty (80S)" — 60S + 40S = 80S ribosome (eukaryote)',
         '★  Clinically important: Antibiotics target prokaryotic ribosomes:',
         '   30S inhibitors: Tetracycline, Aminoglycosides (Gentamicin), Streptomycin',
         '   50S inhibitors: Chloramphenicol, Erythromycin (macrolides), Clindamycin, Linezolid'],
        C_GOLD_LIGHT, C_GOLD, ''))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 5: DNA vs RNA — Comparison
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('5.  DIFFERENCES BETWEEN DNA AND RNA', C_PURPLE))
    story.append(sp(6))

    diff_data = [
        ['Feature', 'DNA', 'RNA'],
        ['Full name', 'Deoxyribonucleic Acid', 'Ribonucleic Acid'],
        ['Sugar', 'Deoxyribose (lacks 2\'–OH)', 'Ribose (has 2\'–OH group)'],
        ['Bases', 'A, T, G, C', 'A, U, G, C  (Uracil replaces Thymine)'],
        ['Strands', 'Double-stranded (dsDNA)', 'Usually single-stranded (can fold on itself)'],
        ['Helix', 'Double helix (B-form)', 'No stable helix; forms hairpin loops, stems'],
        ['Location', 'Nucleus + Mitochondria', 'Nucleus + Cytoplasm + Ribosomes'],
        ['Stability', 'Very stable; long-lived', 'Less stable; shorter half-life; degraded by RNases'],
        ['2\'–OH group', 'Absent (deoxy)', 'Present — makes RNA more reactive and less stable'],
        ['Modified bases', '5-methylcytosine (epigenetics)', 'Many: pseudouridine (ψ), dihydrouridine (D), inosine, 7-methylguanosine'],
        ['Function', 'Permanent genetic information storage; template for replication and transcription', 'Functional intermediary: carries (mRNA), adapts (tRNA), and catalyzes (rRNA) protein synthesis'],
        ['Amount in cell', 'Constant (diploid = 6 pg/cell)', 'Variable; depends on gene expression'],
        ['Synthesis', 'DNA Replication (DNA-dependent DNA Pol)', 'Transcription (DNA-dependent RNA Pol); no primer needed'],
        ['Susceptibility', 'Stable to alkali', 'Hydrolyzed by dilute alkali (2\'–OH cleaves phosphodiester bond)'],
        ['Genetic material', 'In all cellular organisms and most viruses', 'Genetic material in RNA viruses (HIV, influenza, SARS-CoV-2)'],
    ]
    story.append(make_table(diff_data, cw=[W*0.22, W*0.39, W*0.39], hbg=C_PURPLE))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 6: tRNA — Structure & Function
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('6.  tRNA — Structure and Function', C_RED))
    story.append(sp(6))

    story.append(Paragraph('Overview', H2))
    story.append(Paragraph(
        'Transfer RNA (tRNA) is the <b>adaptor molecule</b> of translation. '
        'It decodes the genetic code by carrying a specific amino acid to the ribosome, '
        'where it base-pairs its anticodon with the matching mRNA codon.',
        BODY))
    story.append(sp(4))

    overview = [
        '• Size: <b>73–93 nucleotides</b> (smallest functional RNA in the cell)',
        '• At least <b>20 types</b> of tRNA exist — one for each amino acid',
        '• Some amino acids are carried by multiple tRNAs (<b>isoacceptor tRNAs</b>)',
        '• Charged tRNA (aminoacyl-tRNA) = tRNA with amino acid attached',
        '• The enzyme that attaches amino acid to tRNA: <b>Aminoacyl-tRNA Synthetase</b> (20 types, one per amino acid)',
        '• The Aminoacyl-tRNA synthetase reaction requires <b>ATP → AMP + PPi</b> (consumes 2 high-energy bonds)',
    ]
    for o in overview:
        story.append(Paragraph(o, BUL))
    story.append(sp(8))

    story.append(Paragraph('The Cloverleaf Structure (2D Secondary Structure)', H2))
    story.append(Paragraph(
        'tRNA folds into a <b>cloverleaf</b> shape in 2D due to intramolecular base pairing. '
        'This structure has <b>4 stems</b> and <b>3-4 loops</b>:',
        BODY))
    story.append(sp(6))

    clover_data = [
        ['Structure', 'Base pairs in stem', 'Contents', 'Function'],
        ['Acceptor Stem', '7 bp', "5' end + 3'-CCA (universal)", "3'-CCA-OH is the amino acid attachment site (amino acid links to 3'-OH of ribose of terminal adenosine)"],
        ['D-Arm / D-Stem-Loop', '3-4 bp', 'D-loop contains Dihydrouridine (D) modified base', 'Interaction with aminoacyl-tRNA synthetase for recognition'],
        ['Anticodon Arm', '5 bp', 'Anticodon loop: 7 nt; middle 3 nt = anticodon (5\'–NNN–3\')', 'Anticodon reads mRNA codon by antiparallel complementary base pairing'],
        ['Variable Loop', '0-5 bp (small); up to 21 nt (large)', 'Variable number of nucleotides', 'Varies by tRNA class; used in synthetase recognition in some tRNAs'],
        ['TψC Arm', '5 bp', 'TψC loop contains Ribothymidine (T) and Pseudouridine (ψ)', 'Interacts with ribosome (EF-Tu/EF1A binding region); ensures correct positioning'],
    ]
    story.append(make_table(clover_data, cw=[W*0.20, W*0.16, W*0.28, W*0.36], hbg=C_RED))
    story.append(sp(8))

    story.append(Paragraph('The 3\' CCA End — Universal Feature', H3))
    story.append(Paragraph(
        'ALL tRNAs in ALL organisms end with the sequence <b>3\'-C–C–A–OH</b> at their 3\' terminus. '
        'The amino acid is attached to the <b>2\'–OH or 3\'–OH</b> of the terminal Adenosine by an ester bond. '
        'This CCA sequence is added post-transcriptionally by the enzyme <b>CCA-adding enzyme (tRNA nucleotidyltransferase)</b>.',
        BODY))
    story.append(sp(8))

    story.append(Paragraph('Modified Bases in tRNA', H3))
    mod_data = [
        ['Modified Base', 'Parent Base', 'Location in tRNA', 'Function'],
        ['Dihydrouridine (D)', 'Uridine', 'D-loop', 'Reduces base stacking → allows flexible conformation needed for synthetase recognition'],
        ['Pseudouridine (ψ)', 'Uridine', 'TψC loop', 'Isomeric form of uridine (C5-glycosidic bond instead of N1); stabilizes helix'],
        ['Ribothymidine (T)', 'Thymidine', 'TψC loop', 'Unusual in RNA (T normally only in DNA); ribosome binding'],
        ['Inosine (I)', 'Adenosine', 'Anticodon position 34 (wobble)', 'Wobble base pairing — can pair with U, C, or A on mRNA'],
        ['7-methylguanosine', 'Guanosine', 'Various', 'Part of 5\' cap of mRNA; also in tRNA'],
    ]
    story.append(make_table(mod_data, cw=[W*0.22, W*0.15, W*0.20, W*0.43], hbg=C_RED))
    story.append(sp(6))
    story.append(InfoBox(
        ['★  The Wobble Hypothesis (Crick, 1966):',
         '   The 3rd base of the codon (3rd position) can pair loosely ("wobble") with the 1st base of the anticodon',
         '   This allows ONE tRNA to recognize MULTIPLE codons differing at the 3rd position',
         '   Example: Inosine at anticodon position 34 can pair with U, C, or A in mRNA',
         '   This explains why fewer tRNAs (~45 in humans) are needed than the 61 sense codons'],
        C_ORANGE_LIGHT, C_ORANGE, ''))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 7: tRNA CLOVERLEAF DIAGRAM
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('7.  tRNA CLOVERLEAF STRUCTURE — Diagram', C_RED))
    story.append(sp(10))
    story.append(TRNACloverleaf(width=W, height=490))
    story.append(sp(8))

    story.append(Paragraph('3D Tertiary Structure of tRNA', H2))
    story.append(Paragraph(
        'The cloverleaf folds further into an <b>L-shaped 3D structure</b> (determined by X-ray crystallography). '
        'The L-shape has two functional ends far apart:',
        BODY))
    l_shape = [
        '• <b>One end (acceptor stem)</b>: holds the amino acid at the 3\'–CCA–OH',
        '• <b>Other end (anticodon loop)</b>: reads the mRNA codon — these two ends are ~7 nm apart',
        '• The D-loop and TψC-loop form tertiary contacts with each other, stabilizing the L-shape',
        '• This L-shape is critical for: (1) fitting into the ribosomal A-site, (2) facilitating peptide bond formation',
    ]
    for l in l_shape:
        story.append(Paragraph(l, BUL))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 8: tRNA FUNCTION — Translation
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('8.  tRNA FUNCTION in Translation', C_GREEN))
    story.append(sp(6))

    story.append(Paragraph('Steps of tRNA Action', H2))
    steps = [
        ['Step', 'Process', 'Details'],
        ['1', 'Aminoacylation (Charging)', 'Aminoacyl-tRNA Synthetase attaches correct amino acid to 3\'–OH of tRNA. Requires ATP → AMP + PPi. This step "interprets" the genetic code.'],
        ['2', 'Entry to Ribosome (A-site)', 'Aminoacyl-tRNA enters the A-site (acceptor site) of the ribosome as part of ternary complex with EF-Tu (prokaryote) / EF-1A (eukaryote) + GTP'],
        ['3', 'Codon-Anticodon Recognition', 'Anticodon of tRNA base-pairs with mRNA codon in A-site; GTP hydrolysis confirms correct pairing'],
        ['4', 'Peptide Bond Formation', 'Peptidyl transferase (23S rRNA ribozyme activity!) catalyzes transfer of growing peptide chain from P-site tRNA to amino acid on A-site tRNA'],
        ['5', 'Translocation', 'Ribosome moves 3 nucleotides along mRNA; A-site tRNA moves to P-site; P-site tRNA moves to E-site (exit); new A-site is exposed. Catalyzed by EF-G (prokaryote) / EF-2 (eukaryote) + GTP'],
        ['6', 'Release', 'When stop codon (UAA, UAG, UGA) is in A-site, Release Factors (RF) enter; polypeptide is released; ribosome dissociates'],
    ]
    story.append(make_table(steps, cw=[W*0.06, W*0.24, W*0.70], hbg=C_GREEN))
    story.append(sp(8))

    story.append(Paragraph('Ribosomal Sites for tRNA', H3))
    sites_data = [
        ['Site', 'Name', 'Contains', 'Function'],
        ['A-site', 'Aminoacyl site', 'Incoming aminoacyl-tRNA', 'Accepts new charged tRNA; codon-anticodon recognition'],
        ['P-site', 'Peptidyl site', 'tRNA carrying growing peptide', 'Peptide bond formation occurs here'],
        ['E-site', 'Exit site', 'Uncharged tRNA leaving ribosome', 'Discharged tRNA exits here'],
    ]
    story.append(make_table(sites_data, cw=[W*0.10, W*0.18, W*0.25, W*0.47], hbg=C_GREEN))
    story.append(sp(4))
    story.append(InfoBox(
        ['★  Mnemonic for ribosomal sites: "APE" — A (Aminoacyl) → P (Peptidyl) → E (Exit)',
         '   New tRNA enters A, chain is on P, empty tRNA exits from E',
         '★  Important: Peptidyl transferase activity is in 23S rRNA (large subunit) = a RIBOZYME',
         '   This proves the "RNA World" hypothesis — RNA came before protein'],
        C_GREEN_LIGHT, C_GREEN, ''))
    story.append(PageBreak())

    # ════════════════════════════════════════════════════════════════════════
    #  SECTION 9: MASTER SUMMARY & CLINICAL CORRELATIONS
    # ════════════════════════════════════════════════════════════════════════
    story.append(SectionHeader('9.  MASTER SUMMARY & CLINICAL CORRELATIONS', C_NAVY))
    story.append(sp(6))

    story.append(Paragraph('The Central Dogma of Molecular Biology', H2))
    story.append(Paragraph(
        'The Central Dogma (Francis Crick, 1958) describes the flow of genetic information:',
        BODY))
    story.append(sp(4))
    story.append(Paragraph(
        '  DNA  →(Replication)→  DNA  →(Transcription)→  RNA  →(Translation)→  Protein',
        ParagraphStyle('Central', fontSize=12, fontName='Helvetica-Bold', textColor=C_NAVY,
                       alignment=TA_CENTER, spaceBefore=4, spaceAfter=8)))
    additions = [
        '• <b>Reverse Transcription</b> (RNA → DNA): Retroviruses (HIV) use reverse transcriptase',
        '• <b>RNA Replication</b> (RNA → RNA): RNA viruses (influenza, SARS-CoV-2) use RNA-dependent RNA Pol',
        '• <b>No Protein → Nucleic Acid flow</b> exists in nature (Crick\'s "Weismann barrier")',
    ]
    for a in additions:
        story.append(Paragraph(a, BUL))
    story.append(sp(8))

    story.append(Paragraph('Clinical Correlations', H2))
    clin_data = [
        ['Disease / Application', 'Nucleic Acid Relevance', 'Key Detail'],
        ['HIV / AIDS', 'RNA virus; reverse transcription', 'HIV has RNA genome → Reverse Transcriptase → DNA → integrates as provirus. Drug target: RT inhibitors (AZT, Tenofovir)'],
        ['SARS-CoV-2 (COVID-19)', 'RNA virus; mRNA vaccine', 'mRNA vaccines deliver mRNA encoding spike protein → cell makes protein → immune response'],
        ['Cancer (oncogenes)', 'DNA mutations; altered gene expression', 'Proto-oncogene mutations → overexpression (RAS, MYC, HER2); tumor suppressor loss (p53, RB)'],
        ['Xeroderma Pigmentosum', 'DNA repair defect (NER)', 'Cannot repair UV-induced pyrimidine dimers → extreme sun sensitivity → skin cancer'],
        ['Sickle Cell Disease', 'Point mutation in DNA', 'A→T mutation in β-globin gene codon 6 → GAG (Glu) → GTG (Val) → HbS polymerization'],
        ['SLE (Lupus)', 'Autoantibodies to DNA/RNA', 'Anti-dsDNA antibodies, anti-snRNP (Smith) antibodies are diagnostic markers'],
        ['Ribosomes as antibiotic targets', 'rRNA targeted by antibiotics', '30S: tetracyclines, aminoglycosides | 50S: chloramphenicol, macrolides, linezolid'],
        ['PCR / Molecular Diagnostics', 'DNA amplification', 'Polymerase Chain Reaction amplifies specific DNA sequences for diagnosis (COVID-19 PCR test)'],
        ['Gene Therapy', 'Correcting DNA/RNA defects', 'Delivering correct DNA or using RNA interference (siRNA) to silence disease genes'],
        ['siRNA Therapeutics', 'RNA interference', 'Patisiran (Onpattro) — FDA-approved siRNA for hereditary transthyretin amyloidosis'],
    ]
    story.append(make_table(clin_data, cw=[W*0.26, W*0.22, W*0.52]))
    story.append(sp(8))

    story.append(Paragraph('All Key Mnemonics — Quick Reference', H2))
    mne_data = [
        ['Topic', 'Mnemonic'],
        ['Purines (2-ring bases)', '"PURe As Gold" → PURines = Adenine + Guanine'],
        ['Pyrimidines (1-ring bases)', '"CUT the PY" or "Funny" = Cytosine, Uracil, Thymine'],
        ['DNA only base', '"Thymine Tells DNA" — Thymine is DNA-specific (RNA has Uracil)'],
        ['tRNA loops', '"Departed Anticodons To Variable exits" = D-loop, Anticodon, TψC, Variable'],
        ['Ribosomal sites', '"APE" = A-site (Aminoacyl) → P-site (Peptidyl) → E-site (Exit)'],
        ['Prokaryotic ribosomes', '"50 + 30 = 70" — never actually adds like math but mnemonics are: 50S + 30S = 70S'],
        ['Eukaryotic ribosomes', '"60 + 40 = 80" — 60S + 40S = 80S'],
        ['H-bonds in base pairs', '"AT = 2, GC = 3" — AT has 2 H-bonds, GC has 3 (GC is stronger)'],
        ['Antibiotics on 30S', '"TANK" = Tetracyclines, Aminoglycosides, (strep)tomiaN, Kanamycin'],
        ['Antibiotics on 50S', '"CCLE" = Chloramphenicol, Clindamycin, Linezolid, Erythromycin (macrolides)'],
    ]
    story.append(make_table(mne_data, cw=[W*0.32, W*0.68], hbg=C_PURPLE,
                            alt=C_PURPLE_LIGHT))
    story.append(sp(6))
    story.append(Paragraph(
        'Sources: Thompson & Thompson Genetics and Genomics in Medicine, 9th ed  |  '
        'Basic Medical Biochemistry - A Clinical Approach, 6th ed  |  '
        "Harper's Illustrated Biochemistry, 32nd ed  |  Kaplan & Sadock's Comprehensive Textbook of Psychiatry",
        CAP))

    doc.build(story, onFirstPage=draw_cover, onLaterPages=draw_later)
    print(f'PDF created: {out}')

if __name__ == '__main__':
    build()

cd /home/daytona/workspace/nucleic-acids-guide && python generate_pdf.py 2>&1

ls -lh /home/daytona/workspace/nucleic-acids-guide/Nucleic_Acids_DNA_RNA_StudyGu…

ls -lh /home/daytona/workspace/nucleic-acids-guide/ && ls -lh /home/daytona/work…

python3 -c " from pypdf import PdfReader for f in ['/home/daytona/workspace/nucl…

ls /home/daytona/skills/docx/scripts/office/ && node --version && npm list -g do…

~/nucleic-acids-guide/generate_docx.js

"use strict";
const {
  Document, Packer, Paragraph, TextRun, Table, TableRow, TableCell,
  HeadingLevel, AlignmentType, BorderStyle, WidthType, ShadingType,
  VerticalAlign, PageNumber, Header, Footer, PageBreak,
  TableOfContents, StyleLevel, UnderlineType
} = require("docx");
const fs = require("fs");

// ── Colour palette ──────────────────────────────────────────────────────────
const NAVY    = "0F2D5E";
const BLUE    = "1D4ED8";
const TEAL    = "0D9488";
const RED     = "DC2626";
const PURPLE  = "7C3AED";
const GREEN   = "16A34A";
const ORANGE  = "EA580C";
const GOLD    = "B45309";
const WHITE   = "FFFFFF";
const DARK    = "1E293B";
const GRAY    = "475569";
const LGRAY   = "F1F5F9";
const LBLUE   = "DBEAFE";
const LTEAL   = "CCFBF1";
const LRED    = "FEE2E2";
const LPURPLE = "EDE9FE";
const LGREEN  = "DCFCE7";
const LORANGE = "FFF7ED";
const LGOLD   = "FEF3C7";

// ── Helpers ─────────────────────────────────────────────────────────────────
const pt = (n) => n * 20; // half-points to twips

function h1(text, color = NAVY) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_1,
    spacing: { before: pt(12), after: pt(6) },
    children: [new TextRun({ text, bold: true, color, size: pt(14), font: "Calibri" })],
    shading: { type: ShadingType.SOLID, fill: LBLUE },
  });
}

function h2(text, color = NAVY) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_2,
    spacing: { before: pt(10), after: pt(4) },
    children: [new TextRun({ text, bold: true, color, size: pt(12), font: "Calibri" })],
  });
}

function h3(text, color = BLUE) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_3,
    spacing: { before: pt(8), after: pt(3) },
    children: [new TextRun({ text, bold: true, color, size: pt(11), font: "Calibri" })],
  });
}

function sectionHeader(text, bgColor = NAVY) {
  return new Paragraph({
    spacing: { before: pt(14), after: pt(6) },
    shading: { type: ShadingType.SOLID, fill: bgColor },
    children: [new TextRun({ text: `  ${text}`, bold: true, color: WHITE, size: pt(13), font: "Calibri" })],
  });
}

function body(runs) {
  if (typeof runs === "string") {
    runs = [new TextRun({ text: runs, size: pt(10), font: "Calibri", color: DARK })];
  }
  return new Paragraph({
    spacing: { before: pt(2), after: pt(2), line: 276 },
    children: runs,
  });
}

function bullet(text, level = 0) {
  // Parse **bold** markers
  const children = [];
  const parts = text.split(/(\*\*[^*]+\*\*)/g);
  for (const p of parts) {
    if (p.startsWith("**") && p.endsWith("**")) {
      children.push(new TextRun({ text: p.slice(2,-2), bold: true, size: pt(10), font: "Calibri", color: DARK }));
    } else if (p) {
      children.push(new TextRun({ text: p, size: pt(10), font: "Calibri", color: DARK }));
    }
  }
  return new Paragraph({
    bullet: { level },
    spacing: { before: pt(1), after: pt(1), line: 260 },
    children,
  });
}

function boldBody(text) {
  return new Paragraph({
    spacing: { before: pt(2), after: pt(2) },
    children: [new TextRun({ text, bold: true, size: pt(10), font: "Calibri", color: DARK })],
  });
}

function mnemonic(text) {
  return new Paragraph({
    spacing: { before: pt(3), after: pt(3) },
    shading: { type: ShadingType.SOLID, fill: LPURPLE },
    indent: { left: pt(10) },
    children: [new TextRun({ text: `★  ${text}`, bold: true, size: pt(10), font: "Calibri", color: PURPLE })],
  });
}

function infoBox(lines, bgColor = LBLUE, textColor = NAVY) {
  return lines.map(line =>
    new Paragraph({
      spacing: { before: pt(1), after: pt(1) },
      shading: { type: ShadingType.SOLID, fill: bgColor },
      indent: { left: pt(10) },
      children: [new TextRun({
        text: line,
        size: pt(9.5),
        font: "Calibri",
        color: textColor,
        bold: line.startsWith("★") || line.startsWith("⚠"),
      })],
    })
  );
}

function spacer() {
  return new Paragraph({ spacing: { before: pt(4), after: pt(4) }, children: [new TextRun("")] });
}

function pageBreak() {
  return new Paragraph({ children: [new PageBreak()] });
}

// ── Table builder ─────────────────────────────────────────────────────────
function makeTable(rows, colWidths, headerBg = NAVY) {
  return new Table({
    width: { size: 9300, type: WidthType.DXA },
    margins: { top: 40, bottom: 40, left: 80, right: 80 },
    rows: rows.map((row, ri) =>
      new TableRow({
        children: row.map((cell, ci) => {
          const isHeader = ri === 0;
          const isAlt = !isHeader && ri % 2 === 0;
          const bg = isHeader ? headerBg : (isAlt ? LBLUE : WHITE);
          const textColor = isHeader ? WHITE : DARK;
          const parts = String(cell).split(/(\*\*[^*]+\*\*)/g);
          const runs = parts.map(p => {
            if (p.startsWith("**") && p.endsWith("**")) {
              return new TextRun({ text: p.slice(2,-2), bold: true, size: pt(9), font: "Calibri", color: textColor });
            }
            return new TextRun({ text: p, bold: isHeader, size: pt(9), font: "Calibri", color: textColor });
          });
          return new TableCell({
            width: colWidths ? { size: colWidths[ci], type: WidthType.DXA } : undefined,
            verticalAlign: VerticalAlign.CENTER,
            shading: { type: ShadingType.SOLID, fill: bg },
            borders: {
              top:    { style: BorderStyle.SINGLE, size: 4, color: "CBD5E1" },
              bottom: { style: BorderStyle.SINGLE, size: 4, color: "CBD5E1" },
              left:   { style: BorderStyle.SINGLE, size: 4, color: "CBD5E1" },
              right:  { style: BorderStyle.SINGLE, size: 4, color: "CBD5E1" },
            },
            children: [new Paragraph({
              spacing: { before: 40, after: 40 },
              children: runs,
            })],
          });
        }),
      })
    ),
  });
}

// ════════════════════════════════════════════════════════════════════════════
// DOCUMENT CONTENT
// ════════════════════════════════════════════════════════════════════════════
const children = [];

// ── TITLE PAGE ──────────────────────────────────────────────────────────────
children.push(
  new Paragraph({ spacing: { before: pt(60) }, children: [] }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(20), after: pt(8) },
    shading: { type: ShadingType.SOLID, fill: NAVY },
    children: [new TextRun({ text: "  NUCLEIC ACIDS — DNA & RNA  ", bold: true, color: WHITE, size: pt(28), font: "Calibri" })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(6), after: pt(6) },
    shading: { type: ShadingType.SOLID, fill: BLUE },
    children: [new TextRun({ text: "Complete Study Guide", bold: true, color: WHITE, size: pt(16), font: "Calibri" })],
  }),
  spacer(),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(4), after: pt(4) },
    children: [new TextRun({ text: "Topics Covered:", bold: true, size: pt(11), color: NAVY, font: "Calibri" })],
  }),
);

const topics = [
  "• Structure and Components of DNA",
  "• Functions of DNA",
  "• Types and Functions of RNA",
  "• Differences Between DNA and RNA",
  "• Structure and Function of tRNA",
  "• Cloverleaf Structure of tRNA (Detailed Diagram)",
  "• Modified Bases in RNA",
  "• Clinical Correlations",
];
for (const t of topics) {
  children.push(new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(2), after: pt(2) },
    children: [new TextRun({ text: t, size: pt(11), color: DARK, font: "Calibri" })],
  }));
}

children.push(
  spacer(),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(6) },
    children: [new TextRun({
      text: "Sources: Thompson & Thompson Genetics 9e  |  Basic Medical Biochemistry 6e  |  Harper's Illustrated Biochemistry 32e",
      size: pt(8), color: GRAY, italics: true, font: "Calibri"
    })],
  }),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 1 — NUCLEIC ACIDS OVERVIEW
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("1.  NUCLEIC ACIDS — Overview & Components", NAVY),
  spacer(),
  body("Nucleic acids are biological macromolecules that store and transmit genetic information and direct protein synthesis. There are two types: DNA (Deoxyribonucleic Acid) and RNA (Ribonucleic Acid)."),
  spacer(),
  h2("Building Blocks — Nucleotides"),
  body("A nucleotide = three components joined together:"),
  bullet("**Pentose sugar** — Deoxyribose (DNA) or Ribose (RNA)"),
  bullet("**Nitrogenous base** — Purine or Pyrimidine"),
  bullet("**Phosphate group** — One or more phosphates (mono/di/triphosphate)"),
  body("A nucleoside = sugar + base only (no phosphate). Nucleotides are linked by 3'–5' phosphodiester bonds forming long polynucleotide chains."),
  spacer(),
  h2("Nitrogenous Bases"),
  makeTable([
    ["Type", "Base", "Found in", "Structure", "Pairs with"],
    ["Purine (2-ring)", "Adenine (A)", "DNA & RNA", "6-aminopurine", "T (DNA) / U (RNA)"],
    ["Purine (2-ring)", "Guanine (G)", "DNA & RNA", "2-amino-6-oxopurine", "C"],
    ["Pyrimidine (1-ring)", "Cytosine (C)", "DNA & RNA", "2-oxo-4-aminopyrimidine", "G"],
    ["Pyrimidine (1-ring)", "Thymine (T)", "DNA ONLY", "5-methyluracil", "A (DNA)"],
    ["Pyrimidine (1-ring)", "Uracil (U)", "RNA ONLY", "No methyl group at C5", "A (RNA)"],
  ], [1800, 1100, 1000, 2200, 1000]),
  spacer(),
  mnemonic("Purines = 'PURe As Gold' → Adenine + Guanine  |  Pyrimidines = 'CUT' → Cytosine, Uracil, Thymine"),
  spacer(),
  h2("Watson-Crick Base Pairing"),
  boldBody("A = T  (2 hydrogen bonds)   |   G ≡ C  (3 hydrogen bonds — stronger, higher melting temperature)"),
  body("Higher G+C content = higher melting temperature (Tm) of DNA. Used in molecular biology to estimate DNA stability."),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 2 — DNA STRUCTURE
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("2.  DNA — Structure", BLUE),
  spacer(),
  h2("The Watson-Crick Double Helix Model (1953)"),
  body("DNA exists as a right-handed double helix proposed by James Watson and Francis Crick in 1953, based on X-ray crystallography data by Rosalind Franklin. It resembles a twisted ladder (spiral staircase)."),
  spacer(),
  makeTable([
    ["Feature", "Detail"],
    ["Two strands", "Two antiparallel polynucleotide chains (one runs 5'→3', the other 3'→5')"],
    ["Antiparallel", "5' end of one strand faces the 3' end of the other"],
    ["Backbone", "Sugar-phosphate backbone on the OUTSIDE of the helix"],
    ["Bases", "Nitrogenous bases face INSIDE, stacked perpendicular to helix axis"],
    ["Helix direction", "Right-handed (B-form — most common in cells)"],
    ["Helix diameter", "~2 nm (20 Å)"],
    ["Base pairs per turn", "10 bp per turn (B-DNA)"],
    ["Rise per base pair", "0.34 nm (3.4 Å) between adjacent base pairs"],
    ["Pitch (full turn)", "3.4 nm per complete turn of helix"],
    ["H-bonds", "A=T: 2 H-bonds  |  G≡C: 3 H-bonds (stronger)"],
    ["Major groove", "Wide — accessible to regulatory proteins, restriction enzymes"],
    ["Minor groove", "Narrow — some drugs (e.g. netropsin) and proteins bind here"],
  ], [2800, 6400]),
  spacer(),
  h2("Forms of DNA Double Helix"),
  makeTable([
    ["Form", "Helix", "bp/turn", "Conditions", "Significance"],
    ["B-DNA", "Right-handed", "10", "Physiological (aqueous)", "Most common in living cells — Watson-Crick form"],
    ["A-DNA", "Right-handed", "11", "Dehydrated conditions", "Found in RNA-DNA hybrid duplexes"],
    ["Z-DNA", "Left-handed", "12", "High salt; CG repeats", "May play a role in gene regulation"],
  ], [1200, 1400, 900, 2000, 3200]),
  spacer(),
  h2("DNA Packaging in the Nucleus"),
  bullet("DNA wraps around **histone** proteins (H2A, H2B, H3, H4 ×2 each) forming the **nucleosome** (core particle)"),
  bullet("~147 bp of DNA wraps 1.65 turns around each nucleosome"),
  bullet("Nucleosomes joined by linker DNA (~20-60 bp) + H1 histone = 'beads on a string' (10 nm fiber)"),
  bullet("Further coiling → 30 nm fiber (solenoid) → loops → scaffold → chromosome"),
  bullet("Total compaction: ~2 meters of DNA packed into a ~6 μm nucleus!"),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 3 — DNA FUNCTIONS
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("3.  DNA — Functions", NAVY),
  spacer(),
  makeTable([
    ["Function", "Description", "Mechanism"],
    ["1. Genetic Information Storage", "Carries the hereditary blueprint in the sequence of A, T, G, C", "Linear sequence of codons encodes amino acid sequences of all proteins"],
    ["2. Replication (Self-copying)", "Exact duplication before every cell division", "Semi-conservative: each strand is a template; DNA Pol synthesizes new complementary strand"],
    ["3. Transcription (Gene Expression)", "DNA serves as template for RNA synthesis", "RNA Polymerase reads 3'→5' template strand; produces mRNA 5'→3'"],
    ["4. Mutation & Evolution", "Base sequence changes introduce genetic variation", "Point mutations, insertions, deletions drive evolution and disease"],
    ["5. Recombination", "Genetic diversity via chromosomal crossover in meiosis", "Homologous recombination shuffles alleles between homologous chromosomes"],
    ["6. Gene Regulation", "Controls when and how much protein is made", "Promoters, enhancers, silencers, insulators are regulatory DNA elements"],
  ], [2000, 3000, 4200]),
  spacer(),
  h2("DNA Replication — Key Points"),
  bullet("**Semi-conservative:** Each new DNA = one original strand + one new strand"),
  bullet("**Bidirectional:** Replication forks move from origin (ori) in both directions"),
  bullet("**DNA Pol III** (prokaryotes) / **DNA Pol δ/ε** (eukaryotes) adds nucleotides 5'→3'"),
  bullet("Requires a **RNA primer** — DNA Pol cannot initiate synthesis de novo"),
  bullet("**Leading strand** — synthesized continuously toward the replication fork"),
  bullet("**Lagging strand** — synthesized discontinuously as Okazaki fragments"),
  bullet("**Proofreading** — DNA Pol 3'→5' exonuclease corrects errors (rate ~1 in 10⁹)"),
  spacer(),
  ...infoBox([
    "⚠  DNA Repair Defects — Clinical Correlations:",
    "   Xeroderma Pigmentosum: defective Nucleotide Excision Repair → UV damage → skin cancers",
    "   Lynch syndrome (HNPCC): defective Mismatch Repair → colorectal cancer",
    "   BRCA1/2 mutations: defective Homologous Recombination → breast & ovarian cancer",
  ], LRED, RED),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 4 — RNA TYPES & FUNCTIONS
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("4.  RNA — Types and Functions", TEAL),
  spacer(),
  body("RNA (Ribonucleic Acid) is a single-stranded nucleic acid transcribed from DNA. It serves as the intermediary between the genetic code (DNA) and protein synthesis."),
  spacer(),
  h2("A. Three Major Types of RNA"),
  makeTable([
    ["Type", "Abbrev", "% of RNA", "Location", "Function"],
    ["Messenger RNA", "mRNA", "~3-5%", "Nucleus → Cytoplasm", "Carries genetic message (codons) from DNA to ribosome for translation into protein"],
    ["Ribosomal RNA", "rRNA", "~80%", "Cytoplasm (ribosomes)", "Structural AND catalytic component of ribosomes; 28S/18S/5.8S/5S (eukaryotes)"],
    ["Transfer RNA", "tRNA", "~15%", "Cytoplasm", "Adaptor molecule: carries amino acid to ribosome; anticodon pairs with mRNA codon"],
  ], [1600, 800, 800, 1600, 4400], TEAL),
  spacer(),
  h2("B. Other Regulatory RNA Types"),
  makeTable([
    ["Type", "Abbrev", "Function"],
    ["Small nuclear RNA", "snRNA", "Component of spliceosomes; removes introns from pre-mRNA (RNA splicing)"],
    ["Small nucleolar RNA", "snoRNA", "Directs chemical modifications (methylation, pseudouridylation) of rRNA in nucleolus"],
    ["MicroRNA", "miRNA", "Single-stranded ~22 nt; post-transcriptional gene silencing by binding 3'UTR of target mRNA"],
    ["Small interfering RNA", "siRNA", "Double-stranded ~21 nt; RNA interference (RNAi) — cleaves target mRNA; therapeutic uses"],
    ["Long non-coding RNA", "lncRNA", "Regulates gene expression; X-chromosome inactivation (XIST); chromatin remodeling"],
    ["Ribozyme", "—", "RNA with catalytic activity (self-splicing introns; peptidyl transferase of 23S rRNA)"],
  ], [2000, 900, 6200], TEAL),
  spacer(),
  h2("C. mRNA Structure (Eukaryotic)"),
  makeTable([
    ["Component", "Description", "Function"],
    ["5' Cap (7-methylguanosine)", "Added co-transcriptionally at 5' end", "Protects from degradation; required for ribosome binding"],
    ["5' UTR", "5' of start codon AUG", "Contains Kozak sequence; ribosome binding in eukaryotes"],
    ["Open Reading Frame (ORF)", "AUG (start) → UAA/UAG/UGA (stop)", "Encodes the protein; read as triplet codons"],
    ["3' UTR", "3' of stop codon", "Regulatory; binding site for miRNAs; affects mRNA stability"],
    ["3' Poly-A tail", "~200 adenosine residues added post-transcriptionally", "Protects from degradation; aids nuclear export and translation"],
  ], [2200, 2400, 4600], TEAL),
  spacer(),
  h2("D. Ribosomal RNA (rRNA) — Prokaryote vs Eukaryote"),
  makeTable([
    ["Organism", "Small Subunit", "Large Subunit", "Ribosome", "Notes"],
    ["Prokaryotes (E. coli)", "30S (16S rRNA)", "50S (23S + 5S rRNA)", "70S", "Target of aminoglycosides, tetracyclines (30S); chloramphenicol, macrolides (50S)"],
    ["Eukaryotes (Human)", "40S (18S rRNA)", "60S (28S + 5.8S + 5S rRNA)", "80S", "Targeted by diphtheria toxin (EF-2), ricin (28S rRNA)"],
    ["Mitochondria (Human)", "28S (12S rRNA)", "39S (16S rRNA)", "55S", "Resembles prokaryotic — explains aminoglycoside ototoxicity/nephrotoxicity"],
  ], [1600, 1600, 2200, 900, 3200], TEAL),
  spacer(),
  ...infoBox([
    "★  Antibiotics targeting ribosomes:",
    "   30S inhibitors: Tetracyclines, Aminoglycosides (Gentamicin), Streptomycin",
    "   50S inhibitors: Chloramphenicol, Erythromycin (macrolides), Clindamycin, Linezolid",
    "   Mnemonic: 'TANK' hits 30S | 'CCLE' hits 50S",
  ], LGOLD, GOLD),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 5 — DNA vs RNA
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("5.  DIFFERENCES BETWEEN DNA AND RNA", PURPLE),
  spacer(),
  makeTable([
    ["Feature", "DNA", "RNA"],
    ["Full name", "Deoxyribonucleic Acid", "Ribonucleic Acid"],
    ["Sugar", "Deoxyribose (lacks 2'–OH)", "Ribose (has 2'–OH group)"],
    ["Bases", "A, T, G, C", "A, U, G, C  (Uracil replaces Thymine)"],
    ["Strands", "Double-stranded (dsDNA)", "Usually single-stranded (can fold on itself)"],
    ["Helix", "Double helix (right-handed B-form)", "No stable helix; forms hairpin loops, stems"],
    ["Location", "Nucleus + Mitochondria", "Nucleus + Cytoplasm + Ribosomes"],
    ["Stability", "Very stable; long-lived", "Less stable; shorter half-life; degraded by RNases"],
    ["2'–OH group", "Absent (deoxy = more stable)", "Present — makes RNA more reactive and less stable"],
    ["Modified bases", "5-methylcytosine (epigenetics; CpG)", "Many: pseudouridine (ψ), dihydrouridine (D), inosine, 7-methylguanosine"],
    ["Function", "Permanent genetic information storage; template", "Functional intermediary: carries (mRNA), adapts (tRNA), catalyzes (rRNA)"],
    ["Amount in cell", "Constant (diploid = 6 pg/cell)", "Variable; depends on level of gene expression"],
    ["Synthesis", "DNA Replication (DNA-dependent DNA Pol)", "Transcription (DNA-dependent RNA Pol); no primer needed"],
    ["Alkali stability", "Stable to dilute alkali", "Hydrolyzed by dilute alkali (2'–OH cleaves phosphodiester bond)"],
    ["As genetic material", "All cellular organisms + most viruses", "RNA viruses: HIV, influenza, SARS-CoV-2"],
  ], [2200, 3300, 3700], PURPLE),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 6 — tRNA STRUCTURE & FUNCTION
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("6.  tRNA — Structure and Function", RED),
  spacer(),
  h2("Overview"),
  body("Transfer RNA (tRNA) is the adaptor molecule of translation. It decodes the genetic code by carrying a specific amino acid to the ribosome, where its anticodon base-pairs with the matching mRNA codon."),
  bullet("**Size:** 73–93 nucleotides (smallest functional RNA in the cell)"),
  bullet("At least **20 types** of tRNA exist — one for each amino acid"),
  bullet("Some amino acids have multiple tRNAs (**isoacceptor tRNAs**)"),
  bullet("**Charged tRNA** (aminoacyl-tRNA) = tRNA with amino acid attached"),
  bullet("**Aminoacyl-tRNA Synthetase** attaches amino acid to tRNA (20 types, one per amino acid)"),
  bullet("The charging reaction requires **ATP → AMP + PPi** (consumes 2 high-energy phosphate bonds)"),
  spacer(),
  h2("The Cloverleaf Structure (2D Secondary Structure)"),
  body("tRNA folds into a cloverleaf shape due to intramolecular base pairing. It has 4 stems and 3-4 loops:"),
  spacer(),
  makeTable([
    ["Structure", "Base Pairs\nin Stem", "Contents", "Function"],
    ["Acceptor Stem", "7 bp", "5' end + universal 3'-CCA", "3'-CCA-OH is the amino acid attachment site; amino acid links to 3'-OH of terminal adenosine"],
    ["D-Arm (D-Stem-Loop)", "3-4 bp", "D-loop: contains Dihydrouridine (D) modified base", "Recognition by aminoacyl-tRNA synthetase"],
    ["Anticodon Arm", "5 bp", "Anticodon loop: 7 nt; middle 3 nt = anticodon (5'-NNN-3')", "Anticodon reads mRNA codon by antiparallel complementary base pairing"],
    ["Variable Loop", "0-5 bp (small)\nor up to 21 nt", "Variable number of nucleotides (4-21)", "Varies by tRNA class; used in synthetase recognition in Class II tRNAs"],
    ["TψC Arm", "5 bp", "TψC loop: contains Ribothymidine (T) and Pseudouridine (ψ)", "Interacts with ribosome (EF-Tu binding); ensures correct positioning in A-site"],
  ], [1800, 1200, 2800, 3400], RED),
  spacer(),
  h3("The 3'-CCA End — Universal Feature"),
  body("ALL tRNAs in ALL organisms end with 3'-C–C–A–OH. The amino acid is attached to the 2'–OH or 3'–OH of the terminal Adenosine by an ester bond. The CCA sequence is added post-transcriptionally by CCA-adding enzyme (tRNA nucleotidyltransferase)."),
  spacer(),
  h3("Modified Bases in tRNA"),
  makeTable([
    ["Modified Base", "Parent Base", "Location", "Function"],
    ["Dihydrouridine (D)", "Uridine", "D-loop", "Reduces base stacking → flexible conformation for synthetase recognition"],
    ["Pseudouridine (ψ)", "Uridine", "TψC loop", "C5-glycosidic bond (instead of N1); stabilizes helix structure"],
    ["Ribothymidine (T)", "Thymidine", "TψC loop", "Unusual in RNA (T normally only in DNA); involved in ribosome binding"],
    ["Inosine (I)", "Adenosine", "Anticodon position 34 (wobble)", "Wobble base: can pair with U, C, or A on mRNA → fewer tRNAs needed"],
    ["7-methylguanosine", "Guanosine", "5' cap of mRNA / tRNA", "Part of mRNA 5' cap; also modifies tRNA"],
  ], [2000, 1400, 1800, 4000], RED),
  spacer(),
  ...infoBox([
    "★  Wobble Hypothesis (Crick, 1966):",
    "   The 3rd codon base pairs loosely ('wobbles') with 1st anticodon base",
    "   ONE tRNA can recognize MULTIPLE codons differing at the 3rd position",
    "   Inosine at anticodon pos. 34 can pair with U, C, or A on mRNA",
    "   This explains why only ~45 tRNAs (humans) read 61 sense codons",
  ], LORANGE, ORANGE),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 7 — tRNA CLOVERLEAF DIAGRAM (ASCII / text-art)
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("7.  tRNA CLOVERLEAF STRUCTURE — Annotated Diagram", RED),
  spacer(),
  new Paragraph({
    spacing: { before: pt(4), after: pt(4) },
    shading: { type: ShadingType.SOLID, fill: "F8FAFC" },
    alignment: AlignmentType.CENTER,
    children: [new TextRun({ text: "tRNA Cloverleaf — 2D Secondary Structure", bold: true, size: pt(13), color: NAVY, font: "Courier New" })],
  }),
  spacer(),
);

// Build the cloverleaf as a monospaced text diagram
const cloverLines = [
  "                     5'─────────────────────────────3'─CCA─OH",
  "                          │  A C C E P T O R  │         │",
  "                          │    S T E M        │    ← Amino acid",
  "                          │   (7 base pairs)  │       attaches",
  "                          │                   │       here",
  "                    ┌─────┘                   └─────┐",
  "                    │                               │",
  "              D-ARM │                               │ TψC-ARM",
  "             (3-4bp)│                               │(5bp)",
  "                    │                               │",
  "              ┌─────┘                               └─────┐",
  "              │   D - L O O P                TψC-LOOP    │",
  "              │  (Dihydrouridine)          (Ribothymidine │",
  "              │                             + Pseudouridine│",
  "              └─────┐                               ┌─────┘",
  "                    │                               │",
  "                    │        VARIABLE LOOP          │",
  "                    │         (4-21 nt)             │",
  "                    └───────────┬───────────────────┘",
  "                                │",
  "                         ANTICODON ARM",
  "                           (5 bp stem)",
  "                                │",
  "                         ┌─────────────┐",
  "                         │             │",
  "                         │  ANTICODON  │",
  "                         │    LOOP     │",
  "                         │  5'-N-N-N-3'│  ← base-pairs with",
  "                         │             │    mRNA CODON",
  "                         └─────────────┘",
];

for (const line of cloverLines) {
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    children: [new TextRun({ text: line, font: "Courier New", size: pt(9.5), color: DARK })],
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children.push(
  spacer(),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(4), after: pt(4) },
    shading: { type: ShadingType.SOLID, fill: LRED },
    children: [new TextRun({
      text: "★  The cloverleaf (2D) folds into an L-shaped 3D structure — acceptor end and anticodon end are ~7 nm apart",
      bold: true, size: pt(10), color: RED, font: "Calibri"
    })],
  }),
  spacer(),
  h2("Summary of tRNA Loops and Arms"),
  makeTable([
    ["Region", "Stem (bp)", "Key Bases", "Function"],
    ["Acceptor stem", "7 bp", "5' end + 3'-CCA", "Amino acid attachment (ester bond to 3'-CCA-OH)"],
    ["D-loop / D-arm", "3-4 bp", "Dihydrouridine (D)", "Synthetase recognition; 'D' stands for dihydrouridine"],
    ["Anticodon loop / arm", "5 bp", "Anticodon (3 nt) + wobble base", "Reads mRNA codon by antiparallel complementary base pairing"],
    ["Variable loop", "0-5 bp", "Variable (4-21 nt)", "Classification of tRNA class; synthetase recognition in Class II"],
    ["TψC loop / arm", "5 bp", "Ribothymidine (T), Pseudouridine (ψ)", "Ribosome binding via EF-Tu; correct A-site positioning"],
  ], [1800, 1200, 2200, 4000], RED),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 8 — tRNA FUNCTION IN TRANSLATION
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("8.  tRNA FUNCTION in Translation", GREEN),
  spacer(),
  h2("Steps of tRNA Action"),
  makeTable([
    ["Step", "Process", "Details"],
    ["1", "Aminoacylation (Charging)", "Aminoacyl-tRNA Synthetase attaches correct amino acid to 3'–OH of tRNA. Requires ATP → AMP + PPi. This step 'reads' the genetic code."],
    ["2", "Entry to Ribosome (A-site)", "Charged tRNA enters A-site as ternary complex with EF-Tu (prokaryote) / EF-1A (eukaryote) + GTP. GTP hydrolysis confirms correct codon-anticodon match."],
    ["3", "Codon-Anticodon Recognition", "Anticodon (3 nt) base-pairs with mRNA codon in A-site; wobble base pairing at 3rd codon position allowed"],
    ["4", "Peptide Bond Formation", "Peptidyl transferase (23S rRNA — a RIBOZYME!) transfers growing peptide from P-site tRNA to amino acid on A-site tRNA"],
    ["5", "Translocation", "Ribosome moves 3 nt along mRNA: A→P→E. EF-G (prokaryote) / EF-2 (eukaryote) + GTP hydrolysis drives this step"],
    ["6", "Release", "Stop codon (UAA, UAG, UGA) at A-site — Release Factors (RF1/2) enter; polypeptide released; ribosome dissociates"],
  ], [400, 2200, 6600], GREEN),
  spacer(),
  h2("Ribosomal Sites for tRNA"),
  makeTable([
    ["Site", "Name", "Contains", "Function"],
    ["A-site", "Aminoacyl site", "Incoming aminoacyl-tRNA", "Accepts new charged tRNA; codon-anticodon recognition occurs here"],
    ["P-site", "Peptidyl site", "tRNA carrying growing peptide chain", "Peptide bond formation occurs; peptide transferred from P to A-site tRNA"],
    ["E-site", "Exit site", "Uncharged (empty) tRNA leaving", "Discharged tRNA exits ribosome from here"],
  ], [900, 1700, 2500, 4100], GREEN),
  spacer(),
  mnemonic("Ribosomal sites: 'APE' = A (Aminoacyl) → P (Peptidyl) → E (Exit)"),
  mnemonic("Peptidyl transferase is a RIBOZYME (23S rRNA) — proves the RNA World hypothesis"),
  pageBreak(),
);

// ════════════════════════════════════════════════════════════════════════════
// SECTION 9 — MASTER SUMMARY & CLINICAL CORRELATIONS
// ════════════════════════════════════════════════════════════════════════════
children.push(
  sectionHeader("9.  MASTER SUMMARY & CLINICAL CORRELATIONS", NAVY),
  spacer(),
  h2("The Central Dogma of Molecular Biology"),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(6), after: pt(8) },
    shading: { type: ShadingType.SOLID, fill: LBLUE },
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  }),
  bullet("**Reverse Transcription** (RNA → DNA): Retroviruses (HIV) use reverse transcriptase"),
  bullet("**RNA Replication** (RNA → RNA): RNA viruses (influenza, SARS-CoV-2) use RNA-dependent RNA Polymerase"),
  bullet("No Protein → Nucleic Acid flow exists in nature ('Weismann barrier')"),
  spacer(),
  h2("Clinical Correlations"),
  makeTable([
    ["Disease / Application", "Nucleic Acid Connection", "Key Detail"],
    ["HIV/AIDS", "RNA virus; reverse transcription", "HIV RNA → Reverse Transcriptase → DNA → integrates as provirus. Target: RT inhibitors (AZT, Tenofovir)"],
    ["SARS-CoV-2 (COVID-19)", "RNA virus; mRNA vaccine", "mRNA vaccines deliver mRNA encoding spike protein → immune response without live virus"],
    ["Cancer", "DNA mutations; altered expression", "Proto-oncogene mutations (RAS, MYC, HER2); tumor suppressor loss (p53, RB, BRCA)"],
    ["Xeroderma Pigmentosum", "DNA repair defect (NER)", "Cannot repair UV-induced thymine dimers → extreme photosensitivity → multiple skin cancers"],
    ["Sickle Cell Disease", "Single nucleotide mutation", "GAG→GTG in β-globin codon 6 → Glu→Val → HbS polymerization under hypoxia"],
    ["SLE (Lupus)", "Autoantibodies to DNA/RNA", "Anti-dsDNA and anti-snRNP (Smith) antibodies are diagnostic markers of SLE"],
    ["Antibiotic targets", "rRNA structural targets", "30S: aminoglycosides, tetracyclines  |  50S: chloramphenicol, macrolides, linezolid"],
    ["PCR Diagnostics", "DNA amplification", "PCR amplifies specific DNA/cDNA sequences — basis of COVID-19 molecular tests, pathogen ID"],
    ["siRNA Therapeutics", "RNA interference", "Patisiran (FDA-approved siRNA) — treats hereditary transthyretin amyloidosis"],
    ["mRNA Vaccines", "Synthetic mRNA delivery", "BNT162b2 (Pfizer), mRNA-1273 (Moderna) — modified mRNA with N1-methylpseudouridine for stability"],
  ], [2000, 2000, 5200]),
  spacer(),
  h2("All Key Mnemonics — Quick Reference"),
  makeTable([
    ["Topic", "Mnemonic"],
    ["Purines (2-ring)", "'PURe As Gold' → Purines = Adenine + Guanine"],
    ["Pyrimidines (1-ring)", "'CUT the PY' = Cytosine, Uracil, Thymine are Pyrimidines"],
    ["DNA-only base", "'Thymine Tells DNA' — Thymine is DNA-specific; RNA has Uracil"],
    ["tRNA loops", "'Departed Anticodons To Variable exits' = D-loop, Anticodon, TψC, Variable"],
    ["Ribosomal sites", "'APE' = A-site (Aminoacyl) → P-site (Peptidyl) → E-site (Exit)"],
    ["Prokaryotic ribosome", "50S + 30S = 70S  (antibiotic target)"],
    ["Eukaryotic ribosome", "60S + 40S = 80S  (diphtheria toxin, ricin target)"],
    ["H-bonds in base pairs", "'AT = 2, GC = 3' — AT has 2, GC has 3 H-bonds (GC is stronger)"],
    ["30S antibiotics", "'TANK' = Tetracyclines, Aminoglycosides, Neomycin, Kanamycin"],
    ["50S antibiotics", "'CCLE' = Chloramphenicol, Clindamycin, Linezolid, Erythromycin"],
    ["Anticodon wobble", "Inosine (I) at pos. 34 pairs with U, C, or A — 'I wobble with everyone'"],
    ["Central Dogma", "DNA → RNA → Protein  ('DRiP' = DNA Replicates in Pairs)"],
  ], [3200, 6000], PURPLE),
  spacer(),
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      text: "Sources: Thompson & Thompson Genetics 9e  |  Basic Medical Biochemistry 6e  |  Harper's Illustrated Biochemistry 32e  |  Kaplan & Sadock's Comprehensive Textbook of Psychiatry",
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  }),
);

// ════════════════════════════════════════════════════════════════════════════
// BUILD DOCUMENT
// ════════════════════════════════════════════════════════════════════════════
const doc = new Document({
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  title: "Nucleic Acids — DNA & RNA Study Guide",
  description: "Complete study guide for Nucleic Acids including DNA structure, RNA types, and tRNA cloverleaf",
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~/carb-studyguide/generate_docx.js

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const fs = require("fs");

const NAVY   = "0F2D5E"; const BLUE   = "1D4ED8"; const TEAL   = "0D9488";
const RED    = "DC2626"; const PURPLE = "7C3AED"; const GREEN  = "16A34A";
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const LGOLD  = "FEF3C7"; const LGRAY  = "F1F5F9";

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const children = [];

// COVER
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    children: [new TextRun({ text: "  CARBOHYDRATES & GLUCOSE METABOLISM  ", bold: true, color: WHITE, size: pt(26), font: "Calibri" })],
  }),
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    children: [new TextRun({ text: "Complete Study Guide — Easy Language", bold: true, color: WHITE, size: pt(14), font: "Calibri" })],
  }),
  spacer(),
);
const coverTopics = [
  "• Classification of Carbohydrates (Homo- & Mucopolysaccharides)",
  "• Fate of Glucose in the Body",
  "• Glycolysis — All 10 Steps, Phases & Energetics",
  "• TCA Cycle (Krebs Cycle) — Steps, Energetics & Importance",
  "• HMP Shunt / Pentose Phosphate Pathway",
  "• Gluconeogenesis — Definition, Precursors & Bypass Steps",
  "• Glycogenesis — Definition & Steps",
  "• Blood Glucose Regulation — Normal Values, Hormones & Mechanisms",
  "• Glucose Tolerance Test (GTT) — Indications, Procedure & Interpretation",
  "• Glycosuria — Causes, Renal Threshold & Tests",
  "• Master Summary — ATP Yield, Regulatory Enzymes, Clinical Diseases, Mnemonics",
];
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children.push(
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  new Paragraph({ alignment: AlignmentType.CENTER, spacing: { before: pt(6) }, children: [new TextRun({ text: "Sources: Basic Medical Biochemistry 6e  |  Guyton & Hall Physiology  |  Tietz Laboratory Medicine 7e", size: pt(8), color: GRAY, italics: true, font: "Calibri" })] }),
  pageBreak(),
);

// ══ SECTION 1: Classification ══════════════════════════════════════════════
children.push(
  sectionHeader("1.  CLASSIFICATION OF CARBOHYDRATES", NAVY),
  spacer(),
  body("Carbohydrates are polyhydroxy aldehydes or ketones — basically sugar molecules of different sizes."),
  spacer(),
  h2("Monosaccharides (Single sugar unit — cannot be hydrolyzed further)"),
  makeTable([
    ["Sugar", "Type", "Key Role"],
    ["Glucose", "Aldohexose", "Primary fuel of the body — 'petrol for a car'"],
    ["Fructose", "Ketohexose", "Fruit sugar; enters glycolysis as Fructose-6-P"],
    ["Galactose", "Aldohexose", "Milk sugar component"],
    ["Ribose", "Aldopentose", "Backbone of RNA, ATP, NAD+, FAD, CoA"],
    ["Deoxyribose", "Deoxypentose", "Backbone of DNA"],
  ], [1800, 1800, 5700]),
  spacer(),
  h2("Disaccharides (Two monosaccharide units)"),
  makeTable([
    ["Name", "Components", "Bond", "Found in"],
    ["Sucrose", "Glucose + Fructose", "α1,β2", "Table sugar"],
    ["Lactose", "Glucose + Galactose", "β1,4", "Milk (lactase deficiency = bloating, diarrhea)"],
    ["Maltose", "Glucose + Glucose", "α1,4", "Malt; starch digestion product"],
  ], [1500, 2000, 1000, 4800]),
  spacer(),
  h2("Homopolysaccharides (All same monomer)"),
  makeTable([
    ["Name", "Monomer", "Linkage", "Location / Function"],
    ["Starch (Amylose)", "Glucose", "α-1,4", "Plant storage; linear chain; digestible"],
    ["Starch (Amylopectin)", "Glucose", "α-1,4 + α-1,6 branches", "Plant storage; branched every 24-30 units"],
    ["Glycogen", "Glucose", "α-1,4 + α-1,6 branches", "Animal storage — liver & muscle; more branched (every 8-10 units)"],
    ["Cellulose", "Glucose", "β-1,4", "Plant cell wall; NOT digestible by humans"],
    ["Dextran", "Glucose", "α-1,6", "Bacterial; used as plasma volume expander"],
    ["Inulin", "Fructose", "β-2,1", "Used to measure GFR (freely filtered, not reabsorbed)"],
    ["Chitin", "N-Acetylglucosamine", "β-1,4", "Insect exoskeletons, fungal cell walls"],
  ], [1600, 1300, 1800, 4600]),
  spacer(),
  h2("Mucopolysaccharides / Glycosaminoglycans (GAGs)"),
  body("Long unbranched chains of repeating disaccharide units (amino sugar + uronic acid). Highly negatively charged — attract water — form gel-like ground substance of connective tissue."),
  spacer(),
  makeTable([
    ["GAG", "Composition", "Location", "Function"],
    ["Hyaluronic acid", "GlcUA + GlcNAc", "Synovial fluid, vitreous humor", "Lubrication, shock absorption, wound healing"],
    ["Chondroitin sulfate", "GlcUA + GalNAc-SO4", "Cartilage, bone, cornea", "Structural support"],
    ["Dermatan sulfate", "IdoUA + GalNAc-SO4", "Skin, blood vessels", "Structural, anticoagulant role"],
    ["Heparin / Heparan sulfate", "IdoUA + GlcNH2", "Mast cells, blood vessel walls", "Anticoagulant (activates antithrombin III)"],
    ["Keratan sulfate", "Galactose + GlcNAc-SO4", "Cornea, cartilage, bone", "Corneal transparency; structural"],
  ], [1800, 2000, 2000, 3500]),
  spacer(),
  ...infoBox([
    "⚠  Mucopolysaccharidoses — deficiency of lysosomal enzymes that degrade GAGs",
    "   → GAGs accumulate in tissues → coarse facies, organomegaly, skeletal deformity",
    "   Hurler syndrome: α-L-iduronidase deficiency (AR)",
    "   Hunter syndrome: iduronate sulfatase deficiency (X-linked recessive)",
  ], LORANGE, ORANGE),
  pageBreak(),
);

// ══ SECTION 2: Fate of Glucose ════════════════════════════════════════════
children.push(
  sectionHeader("2.  FATE OF GLUCOSE IN THE BODY", BLUE),
  spacer(),
  body("After absorption, glucose can be 'spent, saved, or invested':"),
  spacer(),
  makeTable([
    ["Pathway", "Product", "Where", "When / Why"],
    ["Glycolysis → TCA → OXPHOS", "~30-32 ATP", "All cells", "Primary energy source — always active"],
    ["Glycogenesis", "Glycogen", "Liver, Muscle", "Fed state — insulin high"],
    ["HMP Shunt (Pentose Phosphate)", "NADPH + Ribose-5-P", "Liver, RBCs, Adrenal", "Biosynthesis + antioxidant defense"],
    ["Lipogenesis", "Triglycerides", "Liver, Adipose", "Excess glucose; fed state"],
    ["Glucuronate pathway", "Glucuronic acid", "Liver", "Detoxification, GAG synthesis"],
    ["Glycosuria (overflow)", "Lost in urine", "Kidney", "Only if blood glucose > ~180 mg/dL"],
  ], [2200, 1500, 1500, 4100]),
  pageBreak(),
);

// ══ SECTION 3: Glycolysis ════════════════════════════════════════════════
children.push(
  sectionHeader("3.  GLYCOLYSIS — Pathway & Energetics", NAVY),
  spacer(),
  body("**Definition:** Breakdown of 1 glucose (6C) → 2 pyruvate (3C).   **Location:** Cytosol of ALL cells.   **Works with OR without O₂.**"),
  spacer(),
  h2("PHASE 1 — Investment Phase (spends 2 ATP)"),
  makeTable([
    ["Step", "Reaction", "Enzyme", "Key Points"],
    ["1", "Glucose → Glucose-6-P", "Hexokinase (all tissues)\nGlucokinase (liver, β-cells)", "Uses 1 ATP; traps glucose in cell; IRREVERSIBLE\nGlucokinase: high Km, not saturated at normal glucose"],
    ["2", "G6P → Fructose-6-P", "Phosphoglucose isomerase", "Reversible; isomerization"],
    ["3", "F6P → Fructose-1,6-BP", "★ PFK-1 (RATE-LIMITING)", "Uses 1 ATP; IRREVERSIBLE\nActivated: AMP, ADP, F-2,6-BP, insulin\nInhibited: ATP, citrate, glucagon"],
    ["4", "F-1,6-BP → DHAP + G3P", "Aldolase", "Splits 6C into two 3C fragments"],
    ["5", "DHAP ⇌ G3P", "Triose phosphate isomerase", "DHAP converted to G3P — both enter Phase 2"],
  ], [400, 2400, 2200, 4300]),
  spacer(),
  h2("PHASE 2 — Payoff Phase (all steps ×2, earns 4 ATP + 2 NADH)"),
  makeTable([
    ["Step", "Reaction", "Enzyme", "Key Points"],
    ["6", "G3P → 1,3-Bisphosphoglycerate", "G3P Dehydrogenase", "Oxidation step; produces 2 NADH (×2); uses inorganic phosphate"],
    ["7", "1,3-BPG → 3-Phosphoglycerate", "Phosphoglycerate kinase", "2 ATP produced (×2) — substrate-level phosphorylation"],
    ["8", "3-PG → 2-Phosphoglycerate", "Phosphoglycerate mutase", "Shifts phosphate group"],
    ["9", "2-PG → PEP", "Enolase", "Inhibited by fluoride! (why blood glucose tubes have fluoride)"],
    ["10", "PEP → Pyruvate", "★ Pyruvate Kinase", "2 ATP produced (×2); IRREVERSIBLE\nActivated: F-1,6-BP (feedforward)\nInhibited: ATP, alanine, glucagon"],
  ], [400, 2400, 2200, 4300]),
  spacer(),
  h2("Net Energetics of Glycolysis"),
  makeTable([
    ["Product", "Amount", "Notes"],
    ["ATP (net)", "2 ATP", "Substrate-level phosphorylation"],
    ["NADH", "2 NADH", "→ 5 ATP via malate-aspartate shuttle; or 3 ATP via glycerol-3-P shuttle"],
    ["Pyruvate", "2 molecules", "Further oxidized (aerobic) or reduced to lactate (anaerobic)"],
  ], [2000, 1500, 5800]),
  spacer(),
  h2("Fate of Pyruvate"),
  makeTable([
    ["Condition", "Product", "Enzyme", "Significance"],
    ["Aerobic (O₂ present)", "Acetyl-CoA + CO₂ + NADH", "Pyruvate Dehydrogenase Complex\n(cofactors: TPP, lipoate, CoA, FAD, NAD+)", "Enters TCA cycle → ~28 more ATP"],
    ["Anaerobic (no O₂)", "Lactate + NAD+", "Lactate Dehydrogenase (LDH)", "Regenerates NAD+ → glycolysis continues; Cori cycle: lactate → liver → glucose"],
  ], [1800, 2000, 2600, 2900]),
  spacer(),
  mnemonic("Glycolysis steps: 'Goodness Gracious, Father Franklin Did Go By Picking Peas'"),
  mnemonic("Glucose→G6P→F6P→F1,6BP→DHAP/G3P→1,3BPG→3PG→2PG→PEP→Pyruvate"),
  pageBreak(),
);

// ══ SECTION 4: TCA Cycle ═══════════════════════════════════════════════
children.push(
  sectionHeader("4.  TCA CYCLE (Krebs Cycle / Citric Acid Cycle)", GREEN),
  spacer(),
  body("**Location:** Mitochondrial matrix   **Entry:** Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C)"),
  spacer(),
  makeTable([
    ["#", "Reaction", "Enzyme", "Product", "Notes"],
    ["1", "Acetyl-CoA + OAA → Citrate", "Citrate Synthase", "—", "Condensation; inhibited by ATP, NADH, succinyl-CoA"],
    ["2", "Citrate → Isocitrate", "Aconitase", "—", "Via aconitate intermediate; inhibited by fluoroacetate"],
    ["3", "Isocitrate → α-Ketoglutarate", "★ Isocitrate DH (rate-limiting)", "NADH + CO₂", "Activated: ADP, Ca²⁺  |  Inhibited: ATP, NADH"],
    ["4", "α-KG → Succinyl-CoA", "α-KG Dehydrogenase", "NADH + CO₂", "IRREVERSIBLE; same cofactors as PDC; inhibited by NADH, succinyl-CoA"],
    ["5", "Succinyl-CoA → Succinate", "Succinyl-CoA Synthetase", "GTP", "Only substrate-level phosphorylation in TCA"],
    ["6", "Succinate → Fumarate", "Succinate Dehydrogenase", "FADH₂", "Only FAD-linked TCA enzyme; embedded in inner membrane (Complex II)"],
    ["7", "Fumarate → Malate", "Fumarase", "H₂O added", "Trans-addition of water"],
    ["8", "Malate → Oxaloacetate", "Malate Dehydrogenase", "NADH", "OAA regenerated for next turn"],
  ], [300, 2200, 2000, 1000, 3800]),
  spacer(),
  h2("Energetics per Acetyl-CoA (one turn)"),
  makeTable([
    ["Product", "Amount", "ATP Equivalent"],
    ["NADH", "3", "3 × 2.5 = 7.5 ATP"],
    ["FADH₂", "1", "1 × 1.5 = 1.5 ATP"],
    ["GTP", "1", "1 ATP"],
    ["TOTAL", "", "≈ 10 ATP per Acetyl-CoA"],
  ], [2500, 1500, 5300]),
  spacer(),
  h2("Importance of TCA Cycle"),
  bullet("**Primary source** of NADH and FADH₂ → drives oxidative phosphorylation → most body ATP"),
  bullet("**Amphibolic** — both catabolic AND anabolic (breakdown + synthesis)"),
  bullet("Provides **biosynthetic precursors:** OAA→amino acids; α-KG→glutamate; Succinyl-CoA→heme; Citrate→fatty acids"),
  bullet("Two **CO₂** released per turn → exhaled"),
  bullet("**Anaplerotic reactions** replenish cycle intermediates (e.g., Pyruvate Carboxylase: Pyr+CO₂→OAA)"),
  bullet("Ca²⁺ activates 3 key enzymes → couples muscle contraction to energy production"),
  spacer(),
  mnemonic("TCA intermediates: 'Citrate Is Krebs' Starting Substrate For Making OAA'"),
  mnemonic("Citrate → Isocitrate → α-KG → Succinyl-CoA → Succinate → Fumarate → Malate → OAA"),
  pageBreak(),
);

// ══ SECTION 5: HMP Shunt ══════════════════════════════════════════════
children.push(
  sectionHeader("5.  HMP SHUNT (Hexose Monophosphate / Pentose Phosphate Pathway)", PURPLE),
  spacer(),
  body("**Location:** Cytosol   **Active in:** Liver, RBCs, Adrenal cortex, Gonads, Lactating mammary gland"),
  body("**Purpose:** NOT for ATP — for NADPH production (antioxidant + biosynthesis) and Ribose-5-P (nucleotide synthesis)."),
  spacer(),
  h2("Phase 1 — Oxidative Phase (IRREVERSIBLE) → Generates NADPH"),
  makeTable([
    ["Step", "Reaction", "Enzyme", "Products"],
    ["1", "Glucose-6-P → 6-Phosphogluconolactone", "★ G6P Dehydrogenase (rate-limiting)", "NADPH"],
    ["2", "6-Phosphogluconolactone → 6-Phosphogluconate", "Lactonase", "H₂O"],
    ["3", "6-Phosphogluconate → Ribulose-5-P + CO₂", "6-Phosphogluconate Dehydrogenase", "NADPH + CO₂"],
  ], [400, 3200, 2800, 1900]),
  body("**Net per G6P in oxidative phase: 2 NADPH + 1 CO₂ + Ribulose-5-P**"),
  spacer(),
  h2("Phase 2 — Non-Oxidative Phase (REVERSIBLE)"),
  body("Transketolase and Transaldolase reactions shuffle C3-C7 sugar phosphates. Products can re-enter glycolysis as F6P and G3P, or go to nucleotide synthesis."),
  spacer(),
  h2("Functions of NADPH"),
  makeTable([
    ["Function", "Details"],
    ["**RBC protection**", "Reduces glutathione (GSSG → GSH) → neutralizes H₂O₂ → prevents oxidative hemolysis"],
    ["Fatty acid synthesis", "Required by Fatty Acid Synthase in liver and adipose tissue"],
    ["Cholesterol synthesis", "Required by HMG-CoA reductase pathway; all steroid hormone synthesis"],
    ["Phagocyte killing", "NADPH oxidase produces O₂⁻ (superoxide) → oxidative burst to kill bacteria"],
    ["Detoxification", "Cytochrome P450 enzymes in liver use NADPH"],
  ], [2500, 6800]),
  spacer(),
  ...infoBox([
    "⚠  G6PD Deficiency — Most common enzyme deficiency worldwide (X-linked recessive)",
    "   No G6PD → no NADPH → RBCs unprotected → oxidative stress → hemolytic anemia",
    "   Triggers: Primaquine, Dapsone, Sulfonamides, Nitrofurantoin, Fava beans, Infections",
    "   Blood film: Heinz bodies (denatured Hb), bite cells  |  Test: G6PD enzyme assay",
  ], LORANGE, ORANGE),
  pageBreak(),
);

// ══ SECTION 6: Gluconeogenesis ════════════════════════════════════════
children.push(
  sectionHeader("6.  GLUCONEOGENESIS", NAVY),
  spacer(),
  body("**Definition:** Synthesis of glucose from non-carbohydrate precursors. Occurs mainly in **liver** (90%) and **kidney** (10%). Active during fasting, starvation, prolonged exercise."),
  spacer(),
  h2("Non-Carbohydrate Precursors — 'GOAL'"),
  makeTable([
    ["Precursor", "How it enters", "Source", "Clinical Relevance"],
    ["**Lactate**", "Lactate → Pyruvate (LDH)", "Anaerobic muscle, RBCs", "Cori Cycle: muscle lactate → liver → glucose"],
    ["**Amino acids (Alanine)**", "Alanine → Pyruvate (ALT)", "Muscle protein breakdown", "Alanine Cycle: key during fasting / starvation"],
    ["**Glycerol**", "Glycerol → DHAP", "Lipolysis of triglycerides", "Fat stores provide substrate for gluconeogenesis"],
    ["**Odd-chain fatty acids**", "→ Succinyl-CoA → OAA → PEP", "β-oxidation of odd-chain FA", "Only FA that can generate net glucose"],
  ], [1800, 2200, 2000, 3300]),
  body("❌  Even-chain fatty acids CANNOT generate net glucose (Acetyl-CoA → TCA → CO₂, net carbon = 0)"),
  spacer(),
  h2("The Three Unique Bypass Steps"),
  makeTable([
    ["Glycolytic Enzyme (IRREVERSIBLE)", "Problem", "Gluconeogenic Bypass", "Location + Cofactors"],
    ["Pyruvate Kinase\n(PEP → Pyruvate)", "Cannot reverse", "Step 1: Pyruvate Carboxylase (Pyr→OAA)\nStep 2: PEPCK (OAA→PEP)", "PC: mitochondria; needs Biotin + ATP\nPEPCK: cytosol; needs GTP"],
    ["PFK-1\n(F6P → F-1,6-BP)", "Cannot reverse", "Fructose-1,6-Bisphosphatase\n(F-1,6-BP → F6P)", "Cytosol; inhibited by AMP, F-2,6-BP\nActivated by citrate"],
    ["Hexokinase/Glucokinase\n(Glucose → G6P)", "Cannot reverse", "Glucose-6-Phosphatase\n(G6P → Glucose)", "ER membrane; ONLY in liver + kidney\n★ NOT in muscle or brain!"],
  ], [2200, 1500, 2500, 3100]),
  spacer(),
  mnemonic("Gluconeogenic precursors: 'GOAL' = Glycerol, Odd-chain FA, Amino acids, Lactate"),
  pageBreak(),
);

// ══ SECTION 7: Glycogenesis ═══════════════════════════════════════════
children.push(
  sectionHeader("7.  GLYCOGENESIS (Glycogen Synthesis)", BLUE),
  spacer(),
  body("**Definition:** Converting glucose into glycogen for storage. **Where:** Liver (blood glucose buffer) and Skeletal Muscle (local reserve)."),
  spacer(),
  h2("Steps of Glycogenesis"),
  makeTable([
    ["Step", "Reaction", "Enzyme", "Key Detail"],
    ["1", "Glucose → Glucose-6-P", "Hexokinase / Glucokinase", "Uses 1 ATP; traps glucose"],
    ["2", "G6P → Glucose-1-P", "Phosphoglucomutase", "Prepares for activation"],
    ["3", "G1P + UTP → UDP-Glucose + PPi", "UDP-Glucose Pyrophosphorylase", "'Activated glucose' — high-energy form ready to be added to chain"],
    ["4", "UDP-Glucose added to chain", "★ Glycogen Synthase", "Adds via α-1,4 bonds to non-reducing ends; needs glycogenin primer"],
    ["5", "Branch creation (~every 11 residues)", "Branching Enzyme", "Moves 6-7 glucose block → creates α-1,6 branch point; ↑ solubility, ↑ free ends"],
  ], [400, 2200, 2200, 4500]),
  spacer(),
  h2("Regulation of Glycogenesis"),
  makeTable([
    ["State", "Signal", "Effect on Glycogen Synthase", "Result"],
    ["Fed (post-meal)", "Insulin ↑", "Protein phosphatase dephosphorylates → ACTIVE form (a)", "Glycogen stored"],
    ["Fasting / Stress", "Glucagon / Epinephrine ↑", "PKA phosphorylates → INACTIVE (b) form", "Glycogen breakdown"],
    ["Muscle (local)", "Glucose-6-P ↑", "Allosteric activation of inactive form", "Glycogen stored locally"],
  ], [1800, 2000, 3200, 2300]),
  spacer(),
  ...infoBox([
    "★  Key Rule: Glycogen Synthase = ACTIVE when DEPHOSPHORYLATED (insulin state)",
    "   Glycogen Phosphorylase = ACTIVE when PHOSPHORYLATED (glucagon/epinephrine state)",
    "   These pathways are RECIPROCALLY regulated — cannot synthesize and break down simultaneously",
  ], LBLUE, NAVY),
  pageBreak(),
);

// ══ SECTION 8: Blood Glucose Regulation ══════════════════════════════
children.push(
  sectionHeader("8.  BLOOD GLUCOSE REGULATION", NAVY),
  spacer(),
  h2("Normal Values — Must Know!"),
  makeTable([
    ["Condition", "Blood Glucose Level", "Significance"],
    ["**Normal fasting (8h)**", "**70–100 mg/dL**  (3.9–5.6 mmol/L)", "Standard reference range"],
    ["2h post-meal (OGTT)", "< 140 mg/dL (< 7.8 mmol/L)", "Normal postprandial"],
    ["Impaired fasting glucose", "100–125 mg/dL", "Pre-diabetes"],
    ["Impaired glucose tolerance", "140–199 mg/dL at 2h OGTT", "Pre-diabetes"],
    ["Diabetes Mellitus (fasting)", "≥ 126 mg/dL (×2 occasions)", "Diagnostic threshold"],
    ["Diabetes Mellitus (2h OGTT)", "≥ 200 mg/dL", "Diagnostic threshold"],
    ["**Renal threshold**", "**≈ 180 mg/dL**", "Glucose appears in urine above this value"],
    ["Hypoglycemia", "< 70 mg/dL", "Symptoms: sweating, palpitations, confusion, seizures"],
  ], [2500, 2800, 4000]),
  spacer(),
  h2("Hormonal Regulation"),
  makeTable([
    ["Hormone", "Source", "Effect", "Key Actions"],
    ["**Insulin**", "Pancreatic β-cells", "↓ DECREASES", "↑ GLUT4 (muscle/fat), ↑ glycolysis, ↑ glycogenesis, ↑ lipogenesis; ↓ gluconeogenesis, ↓ glycogenolysis"],
    ["**Glucagon**", "Pancreatic α-cells", "↑ INCREASES", "↑ glycogenolysis, ↑ gluconeogenesis; ↓ glycolysis (via ↓ F-2,6-BP)"],
    ["**Epinephrine**", "Adrenal medulla", "↑ INCREASES", "↑ glycogenolysis (liver + muscle), ↑ gluconeogenesis, ↑ lipolysis — rapid emergency response"],
    ["**Cortisol**", "Adrenal cortex", "↑ INCREASES", "↑ gluconeogenesis enzyme expression; ↑ proteolysis; ↓ peripheral glucose uptake"],
    ["**Growth Hormone**", "Anterior pituitary", "↑ INCREASES", "Anti-insulin; ↓ glucose uptake peripherally; ↑ lipolysis; 'diabetogenic'"],
    ["Somatostatin", "Pancreatic δ-cells", "Biphasic", "Inhibits BOTH insulin AND glucagon secretion"],
    ["GLP-1 / GIP (Incretins)", "Gut (L-cells / K-cells)", "↓ Indirectly", "Potentiate insulin release; inhibit glucagon; GLP-1 slows gastric emptying"],
    ["Thyroxine (T₄)", "Thyroid gland", "↑ INCREASES", "↑ glycogenolysis, ↑ gut glucose absorption, ↑ basal metabolic rate"],
  ], [1500, 1600, 1200, 5000]),
  spacer(),
  h2("Response to Hypoglycemia (Sequential Layered Defense)"),
  makeTable([
    ["Timeframe", "Response", "Mechanism"],
    ["Minutes (1st)", "Glucagon ↑", "Glycogenolysis + gluconeogenesis in liver"],
    ["Minutes (2nd)", "Epinephrine ↑", "Emergency glycogenolysis; inhibits insulin secretion"],
    ["Hours (3rd)", "Growth Hormone ↑ + Cortisol ↑", "Reduce peripheral glucose use; ↑ gluconeogenesis; ↑ lipolysis"],
    ["Prolonged fasting", "Hepatic gluconeogenesis only", "After ~30h fast: glycogen depleted → gluconeogenesis is the ONLY glucose source"],
  ], [1800, 2200, 5300]),
  spacer(),
  ...infoBox([
    "★  Quote from Guyton & Hall Physiology:",
    "   'Glucose is the ONLY nutrient that can be used by the brain, retina, and germinal",
    "    epithelium of the gonads in sufficient quantities to supply optimally required energy.'",
    "   This is WHY blood glucose regulation is so critical.",
  ], LBLUE, NAVY),
  pageBreak(),
);

// ══ SECTION 9: GTT ═══════════════════════════════════════════════════
children.push(
  sectionHeader("9.  GLUCOSE TOLERANCE TEST (GTT / OGTT)", GREEN),
  spacer(),
  body("**Purpose:** Assesses the body's ability to handle a standard glucose load. Diagnoses DM, pre-diabetes, and gestational diabetes (GDM)."),
  spacer(),
  h2("Indications for GTT"),
  bullet("Fasting blood glucose borderline (100–125 mg/dL) — suspected pre-diabetes or DM"),
  bullet("**Gestational Diabetes Mellitus (GDM) screening** — 24–28 weeks of pregnancy (MANDATORY)"),
  bullet("HbA1c unreliable (hemolytic anaemia, hemoglobinopathies, iron deficiency)"),
  bullet("Suspected reactive hypoglycemia or insulinoma"),
  bullet("Discordant fasting and random glucose results"),
  spacer(),
  h2("Procedure — Standard 75g OGTT"),
  makeTable([
    ["Step", "Action", "Details"],
    ["Preparation (3 days before)", "Unrestricted diet", "Must eat ≥ 150g carbohydrates/day for 3 days before test"],
    ["Night before", "8–12 hour fast", "Water only; no alcohol, no smoking, no heavy exercise"],
    ["Time = 0 min", "Fasting blood sample drawn", "Record symptoms; test urine for glucose"],
    ["Glucose load", "Drink 75g anhydrous glucose", "Dissolved in 250-300 mL water; consumed within 5 minutes\nChildren: 1.75 g/kg up to max 75g"],
    ["Time = 60 min", "Blood sample drawn", "Required for GDM diagnosis (IADPSG criteria)"],
    ["Time = 120 min", "Blood sample drawn", "Primary diagnostic time point for DM"],
    ["GDM (IADPSG)", "75g load; any ONE value ≥ threshold = GDM", "Fasting ≥ 92  |  1h ≥ 180  |  2h ≥ 153 mg/dL"],
  ], [2000, 2400, 5000]),
  spacer(),
  h2("Interpretation — 75g OGTT (ADA Criteria)"),
  makeTable([
    ["Category", "Fasting", "2-Hour Value", "Action"],
    ["**Normal**", "< 100 mg/dL", "< 140 mg/dL", "Reassure; lifestyle advice"],
    ["Pre-diabetes (IFG)", "100–125 mg/dL", "—", "Lifestyle modification; consider Metformin"],
    ["Pre-diabetes (IGT)", "—", "140–199 mg/dL", "Lifestyle modification; annual follow-up"],
    ["**Diabetes Mellitus**", "**≥ 126 mg/dL**", "**≥ 200 mg/dL**", "Diagnosis confirmed; initiate management"],
  ], [2200, 1500, 1800, 3800], GREEN),
  spacer(),
  h2("Special GTT Curves"),
  makeTable([
    ["Curve Type", "Pattern", "Cause"],
    ["Normal", "Peak ~140 at 1h; returns < 140 by 2h", "Normal insulin response"],
    ["Diabetic", "Exaggerated peak; slow return; still elevated at 2h", "Insulin deficiency or resistance"],
    ["Flat curve", "Minimal rise after glucose load", "Malabsorption, Addison's disease, hypothyroidism"],
    ["Lag storage", "Very high early peak then rapid fall", "Post-gastrectomy, hyperthyroidism"],
    ["Reactive hypoglycemia", "Normal rise then falls < 70 at 3-5h", "Excess insulin; suspect insulinoma"],
  ], [2000, 4000, 3300], GREEN),
  pageBreak(),
);

// ══ SECTION 10: Glycosuria ════════════════════════════════════════════
children.push(
  sectionHeader("10.  GLYCOSURIA", ORANGE),
  spacer(),
  body("**Definition:** Presence of glucose in the urine. Normally ALL filtered glucose is reabsorbed in the proximal convoluted tubule (PCT) via SGLT2 (90%) and SGLT1 (10%)."),
  spacer(),
  makeTable([
    ["Concept", "Value / Details"],
    ["**Renal threshold for glucose**", "**≈ 180 mg/dL** plasma glucose (range 160–200)"],
    ["Tubular maximum (Tm)", "≈ 375 mg/min (range 300–450 mg/min)"],
    ["Normal urinary glucose", "< 0.8 mmol/L (essentially absent on routine dipstick)"],
    ["Reabsorption mechanism", "PCT: SGLT2 (low affinity, high capacity) + SGLT1 (high affinity, low capacity)"],
  ], [3000, 6300]),
  spacer(),
  h2("Causes of Glycosuria"),
  makeTable([
    ["Type", "Blood Glucose", "Cause", "Examples"],
    ["**Hyperglycaemic** (most common)", "HIGH (> 180 mg/dL)", "Blood glucose exceeds Tm → glucose spills over", "DM, Cushing's syndrome, pheochromocytoma, steroid therapy, pancreatitis"],
    ["**Renal glycosuria** (normoglycaemic)", "NORMAL", "Reduced renal threshold / Tm defect", "Benign renal glycosuria (SGLT2 mutation), Fanconi syndrome, SGLT2 inhibitor drugs (gliflozins)"],
    ["Physiological (pregnancy)", "Normal or mildly ↑", "Increased GFR + reduced threshold", "Normal in pregnancy; must rule out GDM"],
    ["Alimentary glycosuria", "Post-meal spike", "Rapid absorption overwhelms threshold transiently", "Post-gastrectomy, rapid gastric emptying"],
  ], [1800, 1500, 2200, 3800]),
  spacer(),
  h2("Tests for Glycosuria"),
  makeTable([
    ["Test", "Principle", "Detects", "Use"],
    ["Glucose oxidase dipstick (specific)", "Enzyme-specific for glucose", "Glucose ONLY", "Routine DM monitoring; most common"],
    ["Benedict's / Fehling's test", "Reduces Cu²⁺ (blue→brick red)", "ALL reducing sugars\n(glucose, galactose, fructose, lactose)", "Neonatal metabolic screening; galactosemia"],
    ["Clinitest tablets", "Chemical reduction", "All reducing sugars", "Largely replaced by dipstick"],
  ], [2200, 1800, 2000, 3300], ORANGE),
  spacer(),
  ...infoBox([
    "⚠  IMPORTANT: In Galactosaemia — Benedict's test POSITIVE but glucose dipstick NEGATIVE",
    "   Because galactose (not glucose) is the reducing sugar present in urine!",
    "   Fanconi syndrome: glycosuria + aminoaciduria + phosphaturia + uricosuria (generalised PCT defect)",
  ], LORANGE, ORANGE),
  pageBreak(),
);

// ══ SECTION 11: Master Summary ════════════════════════════════════════
children.push(
  sectionHeader("11.  MASTER SUMMARY — ATP Yield, Regulatory Enzymes & Mnemonics", NAVY),
  spacer(),
  h2("Complete ATP Yield from 1 Glucose Molecule (Aerobic Oxidation)"),
  makeTable([
    ["Stage", "Process", "Direct ATP", "NADH/FADH₂", "ATP from ETC", "Total"],
    ["Glycolysis", "Glucose → 2 Pyruvate (cytosol)", "2", "2 NADH", "5 (M-A shuttle)", "7"],
    ["Pyruvate → Acetyl-CoA", "PDC × 2 (mitochondria)", "0", "2 NADH", "5", "5"],
    ["TCA Cycle ×2", "2 Acetyl-CoA oxidized", "2 GTP", "6 NADH + 2 FADH₂", "18", "20"],
    ["", "**GRAND TOTAL**", "", "", "", "**≈ 30-32 ATP**"],
  ], [1700, 2200, 1000, 1500, 1300, 1500]),
  spacer(),
  h2("Key Regulatory Enzymes — Quick Reference"),
  makeTable([
    ["Enzyme", "Pathway", "Activated by", "Inhibited by"],
    ["Hexokinase", "Glycolysis", "Glucose", "G6P (product inhibition)"],
    ["Glucokinase", "Glycolysis (liver)", "Glucose (high Km)", "No product inhibition; regulated by GKRP"],
    ["★ PFK-1", "Glycolysis (rate-limiting)", "AMP, ADP, F-2,6-BP, insulin", "ATP, citrate, glucagon"],
    ["Pyruvate Kinase", "Glycolysis", "F-1,6-BP (feedforward)", "ATP, alanine, glucagon (phosphorylation)"],
    ["Pyruvate Dehydrogenase", "Pyr → Acetyl-CoA", "ADP, CoA, NAD+, Ca²+", "ATP, Acetyl-CoA, NADH (product inhibition)"],
    ["★ Isocitrate DH", "TCA (rate-limiting)", "ADP, Ca²+", "ATP, NADH"],
    ["★ G6P Dehydrogenase", "HMP Shunt (rate-limiting)", "NADP+", "NADPH (product inhibition)"],
    ["Pyruvate Carboxylase", "Gluconeogenesis", "Acetyl-CoA (allosteric)", "ADP"],
    ["Fructose-1,6-Bisphosphatase", "Gluconeogenesis", "Citrate", "AMP, F-2,6-BP"],
    ["Glycogen Synthase", "Glycogenesis", "G6P, insulin (via PP)", "PKA phosphorylation (glucagon)"],
    ["Glycogen Phosphorylase", "Glycogenolysis", "AMP, Ca²+, PKA (glucagon)", "G6P, ATP, insulin"],
  ], [2000, 1600, 2500, 3200]),
  spacer(),
  h2("Clinically Important Metabolic Diseases"),
  makeTable([
    ["Disease", "Enzyme Defect", "Key Features"],
    ["G6PD Deficiency", "G6P Dehydrogenase (HMP shunt)", "Episodic hemolytic anemia; X-linked; Heinz bodies; triggered by oxidants"],
    ["Galactosaemia", "Galactose-1-P uridyltransferase", "Neonatal jaundice, cataracts, liver failure; reducing sugar in urine"],
    ["Fructose Intolerance", "Aldolase B (liver)", "Hypoglycemia after fructose; liver damage; avoid sucrose and sorbitol"],
    ["Von Gierke (GSD Ia)", "Glucose-6-Phosphatase", "Fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperlipidemia"],
    ["McArdle (GSD V)", "Muscle Glycogen Phosphorylase", "Exercise intolerance, cramps, myoglobinuria; NO lactate rise on exercise"],
    ["Pyruvate Kinase Deficiency", "Pyruvate Kinase (RBCs)", "Chronic hemolytic anemia; ↑ 2,3-BPG (right shift O₂ curve)"],
    ["Hurler Syndrome", "α-L-Iduronidase", "Coarse facies, corneal clouding, organomegaly, intellectual disability"],
  ], [2000, 2200, 5100]),
  spacer(),
  h2("All Mnemonics — Quick Recall"),
  makeTable([
    ["Topic", "Mnemonic"],
    ["Glycolysis 10 steps", "'Goodness Gracious, Father Franklin Did Go By Picking Peas'\nGlucose → G6P → F6P → F1,6BP → DHAP/G3P → 1,3BPG → 3PG → 2PG → PEP → Pyruvate"],
    ["TCA intermediates", "'Citrate Is Krebs' Starting Substrate For Making OAA'\nCitrate → Isocitrate → α-KG → Succinyl-CoA → Succinate → Fumarate → Malate → OAA"],
    ["Gluconeogenic precursors", "'GOAL' = Glycerol, Odd-chain FA, Amino acids, Lactate"],
    ["Hypoglycemia hormones", "'GECGo' = Glucagon (1st), Epinephrine (2nd), Cortisol (3rd), Growth hormone (4th)"],
    ["Glycogen synthase activity", "'Synthase Dephosphorylated = Active' (insulin)\n'Phosphorylase Phosphorylated = Active' (glucagon/epinephrine)"],
    ["Insulin vs Glucagon", "'INsulin = INto cells = decreases blood glucose'\n'GLUCAgon = GLUCose Agonist = raises blood glucose'"],
    ["Purines", "'PURe As Gold' = Purines: Adenine + Guanine (HMP shunt nucleotide synthesis)"],
  ], [2500, 6800], PURPLE),
  spacer(),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: pt(10) },
    children: [new TextRun({ text: "Sources: Basic Medical Biochemistry 6e  |  Guyton & Hall Textbook of Medical Physiology  |  Tietz Textbook of Laboratory Medicine 7e  |  Goodman & Gilman's Pharmacological Basis of Therapeutics", size: pt(8), italics: true, color: GRAY, font: "Calibri" })],
  }),
);

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node /home/daytona/workspace/nucleic-acids-guide/generate_docx.js 2>&1

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# Fix both files: replace PageNumber with PageNumberElement in the header sed -i…

python3 -c " for path in ['/home/daytona/workspace/nucleic-acids-guide/generate_…

node /home/daytona/workspace/nucleic-acids-guide/generate_docx.js 2>&1

node /home/daytona/workspace/carb-studyguide/generate_docx.js 2>&1

python3 /home/daytona/skills/docx/scripts/office/validate.py /home/daytona/works…