#!/usr/bin/env python3
"""NEET PG Biochemistry Quick Revision PDF Generator"""

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import Flowable
import reportlab.lib.colors as rcolors

OUTPUT = "/home/daytona/workspace/neet-pg-biochem/NEET_PG_Biochemistry_Revision.pdf"

# ── Color palette ──────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A237E")
MED_BLUE    = colors.HexColor("#1565C0")
LIGHT_BLUE  = colors.HexColor("#E3F2FD")
TEAL        = colors.HexColor("#00695C")
TEAL_LIGHT  = colors.HexColor("#E0F2F1")
ORANGE      = colors.HexColor("#E65100")
ORANGE_LIGHT= colors.HexColor("#FFF3E0")
PURPLE      = colors.HexColor("#4A148C")
PURPLE_LIGHT= colors.HexColor("#F3E5F5")
GREEN       = colors.HexColor("#1B5E20")
GREEN_LIGHT = colors.HexColor("#E8F5E9")
RED         = colors.HexColor("#B71C1C")
RED_LIGHT   = colors.HexColor("#FFEBEE")
YELLOW      = colors.HexColor("#F57F17")
YELLOW_LIGHT= colors.HexColor("#FFFDE7")
GREY_BG     = colors.HexColor("#F5F5F5")
WHITE       = colors.white
BLACK       = colors.black

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

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

cover_title = S("CoverTitle", fontSize=32, fontName="Helvetica-Bold",
                textColor=WHITE, alignment=TA_CENTER, spaceAfter=6)
cover_sub   = S("CoverSub",   fontSize=16, fontName="Helvetica",
                textColor=colors.HexColor("#BBDEFB"), alignment=TA_CENTER, spaceAfter=4)
cover_tag   = S("CoverTag",   fontSize=11, fontName="Helvetica-Oblique",
                textColor=colors.HexColor("#90CAF9"), alignment=TA_CENTER)

ch_title    = S("ChTitle",    fontSize=18, fontName="Helvetica-Bold",
                textColor=WHITE, alignment=TA_CENTER, spaceAfter=2, spaceBefore=4)
sec_head    = S("SecHead",    fontSize=13, fontName="Helvetica-Bold",
                textColor=DARK_BLUE, spaceBefore=8, spaceAfter=3)
sub_head    = S("SubHead",    fontSize=11, fontName="Helvetica-Bold",
                textColor=MED_BLUE, spaceBefore=5, spaceAfter=2)
body        = S("Body",       fontSize=9,  fontName="Helvetica",
                textColor=BLACK, spaceBefore=2, spaceAfter=2, leading=13)
bullet      = S("Bullet",     fontSize=9,  fontName="Helvetica",
                textColor=BLACK, spaceBefore=1, spaceAfter=1,
                leftIndent=12, bulletIndent=0, leading=12)
mnemonic    = S("Mnemonic",   fontSize=10, fontName="Helvetica-Bold",
                textColor=ORANGE, spaceBefore=3, spaceAfter=2,
                leftIndent=8, backColor=ORANGE_LIGHT)
exam_tip    = S("ExamTip",    fontSize=9,  fontName="Helvetica-BoldOblique",
                textColor=RED, spaceBefore=2, spaceAfter=2,
                leftIndent=8, backColor=RED_LIGHT)
keypoint    = S("KeyPoint",   fontSize=9,  fontName="Helvetica-Bold",
                textColor=GREEN, spaceBefore=2, spaceAfter=2,
                leftIndent=8, backColor=GREEN_LIGHT)
normal_c    = S("NormC",      fontSize=9,  fontName="Helvetica",
                textColor=BLACK, alignment=TA_CENTER)
normal_b    = S("NormB",      fontSize=9,  fontName="Helvetica-Bold",
                textColor=BLACK, alignment=TA_CENTER)
toc_item    = S("TocItem",    fontSize=10, fontName="Helvetica",
                textColor=DARK_BLUE, spaceBefore=2, spaceAfter=2, leftIndent=16)
toc_head    = S("TocHead",    fontSize=12, fontName="Helvetica-Bold",
                textColor=DARK_BLUE, spaceBefore=4, spaceAfter=2)
map_title   = S("MapTitle",   fontSize=10, fontName="Helvetica-Bold",
                textColor=PURPLE, spaceBefore=3, spaceAfter=2, alignment=TA_CENTER)

# ── Helper Flowables ───────────────────────────────────────────────────────────
def chapter_banner(text, color=MED_BLUE):
    data = [[Paragraph(text, ch_title)]]
    t = Table(data, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("ROUNDEDCORNERS", [6]),
        ("TOPPADDING", (0,0), (-1,-1), 8),
        ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ]))
    return t

def info_box(title, items, bg=LIGHT_BLUE, title_color=MED_BLUE, bullet_char="•"):
    content = [Paragraph(f"<b>{title}</b>", S("IB", fontSize=10, fontName="Helvetica-Bold",
               textColor=title_color, spaceAfter=3))]
    for item in items:
        content.append(Paragraph(f"{bullet_char} {item}", bullet))
    data = [[content]]
    t = Table(data, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("BOX", (0,0), (-1,-1), 0.8, title_color),
        ("TOPPADDING", (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING", (0,0), (-1,-1), 8),
    ]))
    return t

def two_col_table(headers, rows, col_widths=None, header_bg=MED_BLUE):
    if col_widths is None:
        col_widths = [17*cm / len(headers)] * len(headers)
    data = [[Paragraph(f"<b>{h}</b>", S("TH", fontSize=9, fontName="Helvetica-Bold",
             textColor=WHITE, alignment=TA_CENTER)) for h in headers]]
    for i, row in enumerate(rows):
        bg = GREY_BG if i % 2 == 0 else WHITE
        data.append([Paragraph(str(c), S(f"TD{i}", fontSize=8.5, fontName="Helvetica",
                     textColor=BLACK)) for c in row])
    t = Table(data, colWidths=col_widths)
    style = [
        ("BACKGROUND", (0,0), (-1,0), header_bg),
        ("GRID", (0,0), (-1,-1), 0.4, colors.grey),
        ("TOPPADDING", (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING", (0,0), (-1,-1), 5),
    ]
    for i in range(1, len(data)):
        if i % 2 == 0:
            style.append(("BACKGROUND", (0,i), (-1,i), GREY_BG))
    t.setStyle(TableStyle(style))
    return t

def mind_map_box(center, branches):
    """Simple ASCII-style mind map rendered as a styled table."""
    rows = [[Paragraph(f"<b>{center}</b>", map_title)]]
    for branch, items in branches.items():
        items_text = "  |  ".join(items)
        rows.append([Paragraph(f"<b>➤ {branch}:</b>  {items_text}", bullet)])
    data = [row for row in rows]
    flat = [[Paragraph(f"<b>{center}</b>",
             S("MMC", fontSize=11, fontName="Helvetica-Bold", textColor=PURPLE, alignment=TA_CENTER))]]
    for branch, items in branches.items():
        flat.append([Paragraph(f"  ┣━ <b>{branch}</b>: " + " | ".join(items), bullet)])
    t = Table(flat, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (0,0), PURPLE_LIGHT),
        ("BOX", (0,0), (-1,-1), 1, PURPLE),
        ("LINEBELOW", (0,0), (0,0), 1, PURPLE),
        ("TOPPADDING", (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
    ]))
    return t

def sp(): return Spacer(1, 4*mm)
def spm(): return Spacer(1, 2*mm)
def hr(color=MED_BLUE): return HRFlowable(width="100%", thickness=0.8, color=color)

# ══════════════════════════════════════════════════════════════════════════════
# CONTENT BUILDER
# ══════════════════════════════════════════════════════════════════════════════
story = []

# ─── COVER PAGE ───────────────────────────────────────────────────────────────
cover_data = [[
    Spacer(1, 2*cm),
    Paragraph("NEET PG", cover_title),
    Paragraph("BIOCHEMISTRY", S("CT2", fontSize=38, fontName="Helvetica-Bold",
               textColor=WHITE, alignment=TA_CENTER, spaceAfter=6)),
    Paragraph("RAPID REVISION GUIDE", cover_sub),
    Spacer(1, 0.5*cm),
    Paragraph("━━━━━━━━━━━━━━━━━━━━━━━━━━━", S("LD", fontSize=14, textColor=colors.HexColor("#64B5F6"), alignment=TA_CENTER)),
    Spacer(1, 0.5*cm),
    Paragraph("✦  Complete Topic Coverage  ✦  High-Yield Concepts", cover_tag),
    Paragraph("✦  Mnemonics  ✦  Mind Maps  ✦  Exam Tips", cover_tag),
    Paragraph("✦  Recent Exam Questions Highlighted", cover_tag),
    Spacer(1, 1*cm),
    Paragraph("Based on Lippincott | Harper's | Standard PG References", cover_tag),
    Spacer(1, 0.5*cm),
    Paragraph("July 2026 Edition", S("ED", fontSize=10, textColor=colors.HexColor("#90CAF9"), alignment=TA_CENTER)),
]]
cover_table = Table([[item] for item in cover_data[0]], colWidths=[19*cm])
cover_table.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING", (0,0), (-1,-1), 2),
    ("BOTTOMPADDING", (0,0), (-1,-1), 2),
    ("LEFTPADDING", (0,0), (-1,-1), 20),
    ("RIGHTPADDING", (0,0), (-1,-1), 20),
]))
story.append(cover_table)
story.append(PageBreak())

# ─── TABLE OF CONTENTS ────────────────────────────────────────────────────────
story.append(chapter_banner("📋  TABLE OF CONTENTS", DARK_BLUE))
story.append(sp())
toc_items = [
    ("1", "Amino Acids & Proteins", "3"),
    ("2", "Enzymes", "5"),
    ("3", "Carbohydrate Metabolism (Glycolysis, TCA, HMP)", "7"),
    ("4", "Gluconeogenesis & Glycogen Metabolism", "10"),
    ("5", "Lipid Metabolism (FA, Ketones, Cholesterol)", "12"),
    ("6", "Protein & Amino Acid Metabolism", "15"),
    ("7", "Nucleotide Metabolism & DNA/RNA", "17"),
    ("8", "Vitamins (Fat & Water Soluble)", "19"),
    ("9", "Minerals & Trace Elements", "22"),
    ("10", "Hormones & Signal Transduction", "23"),
    ("11", "Hemoglobin & Porphyrin Metabolism", "25"),
    ("12", "Connective Tissue Biochemistry", "27"),
    ("13", "Organ-Specific Biochemistry (Liver, Kidney, Brain)", "28"),
    ("14", "Clinical Biochemistry & Lab Values", "29"),
    ("15", "Molecular Biology & Genetics", "30"),
    ("16", "Inborn Errors of Metabolism", "32"),
    ("17", "Master Mnemonics Quick Reference", "34"),
]
for num, topic, pg in toc_items:
    story.append(Paragraph(f"<b>{num}.</b>  {topic} <font color='grey'>{'.' * (55 - len(topic))} {pg}</font>", toc_item))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 1: AMINO ACIDS & PROTEINS
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 1: AMINO ACIDS & PROTEINS", MED_BLUE))
story.append(sp())

story.append(Paragraph("Classification of Amino Acids", sec_head))
story.append(two_col_table(
    ["Category", "Amino Acids", "Key Feature"],
    [
        ["Non-polar (hydrophobic)", "Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, Trp", "No charge, lipid-loving"],
        ["Polar uncharged", "Ser, Thr, Cys, Tyr, Asn, Gln", "H-bond forming"],
        ["Acidic (neg charge)", "Asp, Glu", "pKa ~4; negative at pH 7.4"],
        ["Basic (pos charge)", "Lys, Arg, His", "pKa >6; positive at pH 7.4"],
        ["Essential (9)", "Phe, Val, Thr, Trp, Ile, Met, His, Arg*, Lys", "Cannot be synthesized"],
        ["Glucogenic only", "Ala, Gly, Ser, Asp, Glu, Gln, Asn, Pro, Val, Met, Arg, His, Cys, Thr", "Enter TCA via OAA/PYR"],
        ["Ketogenic only", "Leu, Lys", "Only ketogenic AAs"],
        ["Both gluco+keto", "Ile, Phe, Trp, Tyr, Thr", "IFTYT"],
    ],
    col_widths=[4*cm, 8*cm, 5*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC: Essential AAs = <b>"PVT TIM HaLL"</b>', mnemonic))
story.append(Paragraph("Phe, Val, Thr, Trp, Ile, Met, His, Arg (semi), Leu, Lys", bullet))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC: Both gluco+ketogenic = <b>"IFTYT"</b>', mnemonic))
story.append(Paragraph("Ile, Phe, Tyr, Thr, Trp", bullet))
story.append(sp())

story.append(Paragraph("Protein Structure Levels", sec_head))
story.append(mind_map_box("PROTEIN STRUCTURE", {
    "1° Structure": ["Peptide bonds", "Sequence of AAs", "Sickle cell - Glu→Val"],
    "2° Structure": ["α-helix (3.6 residues/turn)", "β-sheet", "H-bonds in backbone"],
    "3° Structure": ["Disulfide bonds", "Hydrophobic core", "Overall 3D shape"],
    "4° Structure": ["Multiple subunits", "Hemoglobin (2α+2β)", "Quaternary interactions"],
}))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: Collagen has (Gly-Pro-Hyp)n repeat. Vitamin C needed for hydroxylation of Pro & Lys. Deficiency → Scurvy.", exam_tip))
story.append(Paragraph("⭐ EXAM TIP: Proline breaks α-helix. Glycine is smallest AA (no chiral center).", exam_tip))
story.append(sp())

story.append(Paragraph("Isoelectric Point (pI) Key Points", sec_head))
story.append(info_box("pI Concepts", [
    "pI = pH at which AA carries no net charge (zwitterion)",
    "For neutral AAs: pI = (pKa1 + pKa2) / 2",
    "For acidic AAs (Asp, Glu): pI < 7 (low)",
    "For basic AAs (Lys, Arg, His): pI > 7 (high)",
    "At pH < pI → molecule is positively charged (migrates to cathode)",
    "At pH > pI → molecule is negatively charged (migrates to anode)",
    "Histidine pI ≈ 7.6 (only AA acting as buffer at physiologic pH)",
], bg=LIGHT_BLUE))
story.append(sp())

story.append(Paragraph("Collagen & Special Proteins", sec_head))
story.append(two_col_table(
    ["Protein", "Special Feature", "Clinical Relevance"],
    [
        ["Collagen", "Gly-Pro-Hyp triplet; triple helix", "Scurvy, Ehlers-Danlos, Osteogenesis imperfecta"],
        ["Elastin", "Rich in Gly, Ala, Val; cross-linked by lysyl oxidase", "Marfan syndrome (fibrillin defect)"],
        ["Keratin", "α-helical; rich in Cys (disulfide bonds)", "Hair, nails, skin"],
        ["Myosin/Actin", "Contractile proteins", "Muscle diseases"],
        ["Immunoglobulins", "Y-shaped; 2H + 2L chains; IgG crosses placenta", "Antibody structure"],
        ["Hemoglobin", "2α+2β; heme with Fe²⁺", "HbS, HbF, Thalassemia"],
    ],
    col_widths=[3.5*cm, 7.5*cm, 6*cm]
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 2: ENZYMES
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 2: ENZYMES", TEAL))
story.append(sp())

story.append(Paragraph("Enzyme Kinetics (Michaelis-Menten)", sec_head))
story.append(info_box("Key Equations & Concepts", [
    "V = Vmax[S] / (Km + [S])   ← Michaelis-Menten equation",
    "Km = [S] at which V = Vmax/2 → measure of enzyme-substrate AFFINITY",
    "Low Km = High affinity | High Km = Low affinity",
    "Vmax = maximum velocity (proportional to enzyme concentration)",
    "Kcat (turnover number) = Vmax / [Enzyme total]",
    "Efficiency = Kcat/Km",
    "Lineweaver-Burk plot: double reciprocal (1/V vs 1/[S])",
], bg=TEAL_LIGHT, title_color=TEAL))
story.append(sp())

story.append(Paragraph("Types of Enzyme Inhibition", sec_head))
story.append(two_col_table(
    ["Type", "Km", "Vmax", "Example", "Antidote/Note"],
    [
        ["Competitive", "↑ (increases)", "No change", "Methotrexate/DHFR; Statins/HMG-CoA red.", "Overcome by ↑[S]; same Vmax"],
        ["Non-competitive", "No change", "↓ (decreases)", "Heavy metals, Pb on ALA dehydratase", "Cannot overcome; Km unchanged"],
        ["Uncompetitive", "↓ (decreases)", "↓ (decreases)", "Inhibits ES complex", "Parallel shift in LB plot"],
        ["Mixed", "Changes", "↓ (decreases)", "Binds free E and ES", "Variable effect"],
        ["Irreversible", "N/A", "↓ permanently", "Organophosphates/AChE; Aspirin/COX", "Covalent bond; need new enzyme"],
        ["Suicide inhibitor", "N/A", "↓ permanently", "5-FU → FdUMP (TS); Aspirin", "Mechanism-based"],
    ],
    col_widths=[3.5*cm, 2.5*cm, 2.5*cm, 4.5*cm, 4*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Competitive inhibition: <b>"C for COMPETE - Same Vmax, Higher Km"</b>', mnemonic))
story.append(sp())

story.append(Paragraph("Enzyme Regulation", sec_head))
story.append(info_box("Allosteric & Covalent Regulation", [
    "Allosteric enzymes: Sigmoidal kinetics, NOT obeying Michaelis-Menten",
    "Positive allosteric activators: shift curve LEFT (↓ Km apparent)",
    "Negative allosteric inhibitors: shift curve RIGHT (↑ Km apparent)",
    "Phosphorylation/dephosphorylation: most common covalent regulation",
    "Glycogen phosphorylase: ACTIVE when phosphorylated (kinase adds P)",
    "Glycogen synthase: INACTIVE when phosphorylated",
    "Zymogen (proenzyme): inactive precursor (e.g., pepsinogen→pepsin, trypsinogen→trypsin)",
    "Feedback inhibition: end product inhibits first committed enzyme",
], bg=TEAL_LIGHT, title_color=TEAL))
story.append(sp())

story.append(Paragraph("Clinically Important Enzymes", sec_head))
story.append(two_col_table(
    ["Enzyme", "Reaction / Role", "Clinical Note"],
    [
        ["LDH (LD)", "Lactate ↔ Pyruvate", "MI: LDH1>LDH2 (flipped); LDH5 in liver disease"],
        ["CK-MB", "Phosphocreatine → ATP", "Best early marker of MI; peaks 24h"],
        ["Troponin I/T", "Cardiac muscle marker", "Most specific for MI; stays elevated 7-10 days"],
        ["AST/SGOT", "Aspartate + α-KG → OAA", "Liver, heart, muscle; non-specific"],
        ["ALT/SGPT", "Alanine + α-KG → Pyruvate", "Most specific for liver injury"],
        ["GGT", "γ-Glutamyl transfer", "Elevated in alcoholic liver disease"],
        ["Alkaline Phosphatase", "Hydrolyzes phosphate esters", "Bone, liver, placenta; ↑ in cholestasis & bone disease"],
        ["Amylase/Lipase", "Starch/fat digestion", "Pancreatitis; Lipase more specific"],
        ["ACE", "Angiotensin I → II", "↑ in sarcoidosis"],
        ["G6PD", "G6P → 6-PGL (HMP shunt)", "Deficiency → hemolytic anemia (Heinz bodies)"],
        ["Hexokinase/Glucokinase", "Glucose → G6P", "HK: low Km (all tissues); GK: high Km (liver/β-cell)"],
    ],
    col_widths=[4*cm, 6*cm, 7*cm]
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 3: CARBOHYDRATE METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 3: CARBOHYDRATE METABOLISM", colors.HexColor("#1565C0")))
story.append(sp())

story.append(Paragraph("Glycolysis - Key Points", sec_head))
story.append(mind_map_box("GLYCOLYSIS (Embden-Meyerhof)", {
    "Location": ["Cytoplasm (all tissues)"],
    "Net Yield (aerobic)": ["2 ATP", "2 NADH", "2 Pyruvate"],
    "Net Yield (anaerobic)": ["2 ATP", "2 Lactate", "No NADH net"],
    "Irreversible steps (3)": ["Hexokinase/Glucokinase", "PFK-1 (rate-limiting)", "Pyruvate kinase"],
    "Activators of PFK-1": ["AMP, ADP, F2,6-BP, Pi"],
    "Inhibitors of PFK-1": ["ATP, citrate, H+"],
    "Activated by insulin": ["Glucokinase, PFK-1, Pyruvate kinase"],
}))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: PFK-1 is the RATE-LIMITING enzyme of glycolysis. F-2,6-BP is the most potent activator (made by PFK-2, activated by insulin).", exam_tip))
story.append(Paragraph("⭐ EXAM TIP: Pyruvate kinase deficiency → hemolytic anemia. Most common enzyme deficiency causing HA after G6PD deficiency.", exam_tip))
story.append(sp())

story.append(Paragraph("Pyruvate Fate", sec_head))
story.append(two_col_table(
    ["Condition", "Pyruvate Fate", "Enzyme / Coenzymes"],
    [
        ["Aerobic (mitochondria)", "→ Acetyl-CoA", "Pyruvate dehydrogenase (PDH); B1,B2,B3,B5,Lipoic acid"],
        ["Anaerobic / RBCs", "→ Lactate", "Lactate dehydrogenase (LDH)"],
        ["Liver (gluconeogenesis)", "→ OAA", "Pyruvate carboxylase; Biotin (B7), ATP"],
        ["Transamination", "→ Alanine", "Alanine aminotransferase (ALT); B6"],
    ],
    col_widths=[4*cm, 5*cm, 8*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC PDH cofactors: <b>"Tender Loving Care For Nancy" = TPP, Lipoate, CoA, FAD, NAD+</b>', mnemonic))
story.append(sp())

story.append(Paragraph("TCA Cycle (Krebs Cycle)", sec_head))
story.append(info_box("TCA Cycle High-Yield Facts", [
    "Location: Mitochondrial matrix",
    "1 Acetyl-CoA → 3 NADH + 1 FADH2 + 1 GTP + 2 CO2",
    "Rate-limiting enzyme: Isocitrate dehydrogenase",
    "Energy yield per glucose (via TCA): 6 NADH + 2 FADH2 + 2 GTP",
    "α-Ketoglutarate dehydrogenase: same cofactors as PDH (TPP, Lipoate, CoA, FAD, NAD+)",
    "Succinyl-CoA synthetase: only substrate-level phosphorylation in TCA → GTP",
    "Anaplerotic reactions: replenish TCA intermediates (e.g., pyruvate → OAA)",
    "INHIBITORS: Fluoroacetate (→ fluorocitrate, blocks aconitase) - POISONING",
    "Thiamine (B1) deficiency → PDH & α-KG dehydrogenase fail → ↑ pyruvate & lactate",
], bg=LIGHT_BLUE))
story.append(sp())

story.append(Paragraph("HMP Shunt (Pentose Phosphate Pathway)", sec_head))
story.append(info_box("HMP Shunt Key Points", [
    "Location: Cytoplasm; most active in liver, RBCs, adrenal cortex, testes",
    "Purpose: Produce NADPH + Ribose-5-phosphate",
    "NADPH uses: Fatty acid synthesis, cholesterol synthesis, steroid synthesis, glutathione reduction, cytochrome P450",
    "Ribose-5-P uses: Nucleotide synthesis, DNA/RNA",
    "Rate-limiting enzyme: G6PD (Glucose-6-phosphate dehydrogenase)",
    "G6PD deficiency: X-linked recessive; hemolytic anemia with oxidative stress (primaquine, dapsone, infections)",
    "Heinz bodies = denatured Hb in G6PD deficiency",
    "G6PD is MOST COMMON enzyme deficiency worldwide",
], bg=GREEN_LIGHT, title_color=GREEN))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: G6PD deficiency is X-linked recessive. Triggers: antimalarials (primaquine, chloroquine), sulfonamides, dapsone, fava beans, infections.", exam_tip))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 4: GLUCONEOGENESIS & GLYCOGEN
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 4: GLUCONEOGENESIS & GLYCOGEN METABOLISM", colors.HexColor("#0277BD")))
story.append(sp())

story.append(Paragraph("Gluconeogenesis", sec_head))
story.append(two_col_table(
    ["Step (Bypasses Glycolysis)", "Enzyme", "Location", "Cofactor/Note"],
    [
        ["Pyruvate → OAA", "Pyruvate carboxylase", "Mitochondria", "Biotin; activated by Acetyl-CoA"],
        ["OAA → PEP", "PEPCK", "Cytoplasm", "GTP; induced by glucagon/cortisol"],
        ["F1,6-BP → F6P", "Fructose-1,6-bisphosphatase", "Cytoplasm", "Inhibited by AMP, F2,6-BP"],
        ["G6P → Glucose", "Glucose-6-phosphatase", "ER (liver, kidney)", "Absent in muscle & brain!"],
    ],
    col_widths=[4.5*cm, 4.5*cm, 3.5*cm, 4.5*cm]
))
story.append(sp())
story.append(info_box("Gluconeogenesis Key Substrates & Regulation", [
    "Substrates: Lactate (Cori cycle), Alanine (glucose-alanine cycle), Glycerol, Odd-chain FA → Propionyl-CoA → Succinyl-CoA",
    "EVEN chain fatty acids CANNOT be substrate (net no OAA formed from Acetyl-CoA)",
    "Occurs in: Liver (primary), kidney (during prolonged fasting)",
    "Stimulated by: Glucagon, cortisol, epinephrine; FASTING state",
    "Inhibited by: Insulin, alcohol (↑ NADH → pyruvate→lactate, not OAA)",
    "Cori cycle: Lactate from muscle → Liver → Glucose (costs 4 ATP net)",
    "Glucose-alanine cycle: Alanine from muscle → Liver → Glucose + Urea",
]))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Gluconeogenesis substrates: <b>"GOAL" = Glycerol, OAA precursors (odd-chain FA), Amino acids (glucogenic), Lactate</b>', mnemonic))
story.append(sp())

story.append(Paragraph("Glycogen Metabolism", sec_head))
story.append(two_col_table(
    ["Process", "Key Enzyme", "Regulation", "Activator/Inhibitor"],
    [
        ["Glycogen synthesis", "Glycogen synthase", "Dephosphorylated = ACTIVE", "Insulin activates; glucagon/epi inhibits"],
        ["Glycogenolysis", "Glycogen phosphorylase", "Phosphorylated = ACTIVE", "Glucagon, epi activate; insulin inhibits"],
        ["Branching", "Branching enzyme (amylo-1,4→1,6)", "—", "Deficiency → Andersen disease"],
        ["Debranching", "Debranching enzyme (2 activities)", "—", "Deficiency → Cori disease (Type III)"],
        ["Priming", "Glycogenin", "Self-glucosylates", "Initiates glycogen core"],
    ],
    col_widths=[3.5*cm, 4.5*cm, 4.5*cm, 4.5*cm]
))
story.append(sp())

story.append(Paragraph("Glycogen Storage Diseases (GSD)", sec_head))
story.append(two_col_table(
    ["Type", "Name", "Enzyme Deficiency", "Features"],
    [
        ["Type I", "Von Gierke", "G6Pase (liver)", "Severe hypoglycemia, hepatomegaly, ↑lactate, ↑uric acid, ↑triglycerides"],
        ["Type II", "Pompe", "Acid maltase (α-1,4 glucosidase)", "Cardiomegaly, muscle weakness; LYSOSOMAL storage"],
        ["Type III", "Cori", "Debranching enzyme", "Milder than Type I; limit dextrin accumulates"],
        ["Type IV", "Andersen", "Branching enzyme", "Cirrhosis, liver failure"],
        ["Type V", "McArdle", "Muscle phosphorylase", "Exercise intolerance, myoglobinuria; NO ↑ lactate with exercise"],
        ["Type VI", "Hers", "Liver phosphorylase", "Hepatomegaly, mild hypoglycemia"],
        ["Type VII", "Tarui", "PFK (muscle)", "Like McArdle; hemolytic anemia"],
    ],
    col_widths=[2cm, 3cm, 5*cm, 7*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC GSD: <b>"Very Poor Carbohydrate Metabolism, Abnormal Hepatic Thinking"</b> → Type I,II,III,IV,V,VI,VII', mnemonic))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 5: LIPID METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 5: LIPID METABOLISM", colors.HexColor("#4527A0")))
story.append(sp())

story.append(Paragraph("Fatty Acid Synthesis vs. Beta-Oxidation", sec_head))
story.append(two_col_table(
    ["Feature", "FA Synthesis", "β-Oxidation"],
    [
        ["Location", "Cytoplasm", "Mitochondrial matrix"],
        ["Carrier", "ACP (acyl carrier protein)", "CoA"],
        ["Hydrogen carrier", "NADPH (from HMP shunt)", "FAD, NAD+"],
        ["Rate-limiting enzyme", "Acetyl-CoA carboxylase (ACC)", "CPT-I (carnitine transport)"],
        ["Key intermediate", "Malonyl-CoA", "Acyl-carnitine"],
        ["Activated by", "Insulin, citrate", "Glucagon, epinephrine, fasting"],
        ["Inhibited by", "Glucagon, palmitoyl-CoA", "Malonyl-CoA (inhibits CPT-I)"],
        ["Cofactors", "Biotin (ACC), NADPH", "FAD, NAD+, CoA, Carnitine"],
    ],
    col_widths=[4*cm, 6.5*cm, 6.5*cm]
))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: Malonyl-CoA inhibits CPT-I → prevents FA from entering mitochondria → prevents β-oxidation when FA synthesis is active. This is a key regulatory cross-talk!", exam_tip))
story.append(sp())

story.append(Paragraph("Ketone Body Metabolism", sec_head))
story.append(info_box("Ketogenesis & Ketolysis", [
    "Ketogenesis occurs in: LIVER mitochondria ONLY",
    "Ketone bodies: Acetoacetate (primary), β-hydroxybutyrate (transport form), Acetone (exhaled)",
    "Substrate: Acetyl-CoA (from β-oxidation in fasting/DKA)",
    "Key enzyme (synthesis): HMG-CoA synthase (mitochondrial)",
    "Key enzyme (use): Succinyl-CoA acetoacetate-CoA transferase (thiophorase) - ABSENT in liver",
    "Hence liver PRODUCES but CANNOT USE ketone bodies",
    "Brain uses ketones during prolonged fasting (after 3-4 days)",
    "RBCs CANNOT use ketones (no mitochondria)",
    "DKA: insulin deficiency → uncontrolled ketogenesis → anion gap metabolic acidosis",
    "Smell: Fruity breath (acetone) in DKA",
], bg=PURPLE_LIGHT, title_color=PURPLE))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC: <b>"Liver Makes Ketones but Cannot Consume them" (LMKCC)</b>', mnemonic))
story.append(sp())

story.append(Paragraph("Cholesterol Metabolism", sec_head))
story.append(info_box("Cholesterol Synthesis Key Points", [
    "All carbons of cholesterol come from Acetyl-CoA",
    "Rate-limiting enzyme: HMG-CoA reductase (in ER of liver)",
    "Statins: Competitive inhibitors of HMG-CoA reductase",
    "Regulation: Insulin and T3 stimulate; glucagon and cholesterol inhibit",
    "Bile acids: Primary (cholic, chenodeoxycholic) → Secondary (deoxycholic, lithocholic) by gut bacteria",
    "Bile acid sequestrants (cholestyramine): ↓ bile acid reabsorption → ↑ HMG-CoA reductase → ↑ LDL receptors",
    "Cholesterol → Steroid hormones, Bile acids, Vitamin D, Cell membranes",
]))
story.append(sp())

story.append(Paragraph("Lipoproteins", sec_head))
story.append(two_col_table(
    ["Lipoprotein", "Origin", "Main Lipid", "Key Apo", "Function"],
    [
        ["Chylomicron", "Intestine", "TG (dietary)", "ApoB-48, ApoC-II, ApoE", "Dietary fat transport"],
        ["VLDL", "Liver", "TG (endogenous)", "ApoB-100, ApoC-II, ApoE", "Endogenous TG transport"],
        ["IDL", "VLDL remnant", "TG + cholesterol", "ApoB-100, ApoE", "Intermediate"],
        ["LDL", "VLDL/IDL", "Cholesterol", "ApoB-100", "Delivers cholesterol to tissues"],
        ["HDL", "Liver/intestine", "Protein (dense)", "ApoA-I (activates LCAT)", "Reverse cholesterol transport"],
    ],
    col_widths=[3cm, 3*cm, 3*cm, 4*cm, 4*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Lipoprotein density order: <b>"Chunky Villagers Ignore Large Healthy People"</b> = Chylomicron → VLDL → IDL → LDL → HDL (density increases ↑)', mnemonic))
story.append(Paragraph("⭐ EXAM TIP: ApoC-II activates lipoprotein lipase (LPL). Deficiency → familial hyperchylomicronemia. ApoE is needed for remnant clearance.", exam_tip))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 6: PROTEIN & AMINO ACID METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 6: PROTEIN & AMINO ACID METABOLISM", TEAL))
story.append(sp())

story.append(Paragraph("Urea Cycle", sec_head))
story.append(info_box("Urea Cycle Key Facts", [
    "Location: Liver (1st 2 steps in mitochondria, rest in cytoplasm)",
    "Purpose: Disposal of excess nitrogen as non-toxic UREA",
    "Net: 2 NH3 + CO2 → Urea + H2O (costs 3 ATP)",
    "Rate-limiting enzyme: CPS-I (Carbamoyl phosphate synthetase I) - mitochondrial",
    "CPS-I activated by N-acetylglutamate (NAG); inhibited in hyperammonemia",
    "Ornithine is the carrier/regenerated at end",
    "Steps: NH3+CO2→Carbamoyl-P → Citrulline → Argininosuccinate → Arginine → Ornithine + Urea",
    "Hyperammonemia: lethargy, vomiting, cerebral edema; elevated glutamine in CSF/plasma",
]))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Urea cycle: <b>"Ordinarily, Careless Crappers Are Also Arrogant Urologists"</b>', mnemonic))
story.append(Paragraph("Ornithine → Carbamoyl-P → Citrulline → Argininosuccinate → Arginine → (Arginase) → Urea + Ornithine", bullet))
story.append(sp())

story.append(Paragraph("Important Amino Acid Metabolism", sec_head))
story.append(two_col_table(
    ["Amino Acid", "Key Metabolic Pathway", "Clinical Disorder / Note"],
    [
        ["Phenylalanine", "Phe → Tyr (PAH, BH4 cofactor)", "PKU: PAH deficiency; musty odor, intellectual disability"],
        ["Tyrosine", "Tyr → Dopamine → NE → Epi; Tyr→Melanin; Tyr→T3/T4", "Tyrosinemia; albinism (tyrosinase deficiency)"],
        ["Tryptophan", "Trp → Serotonin → Melatonin; Trp → Niacin (B3)", "Hartnup disease; carcinoid tumor (↑5-HIAA)"],
        ["Methionine", "Met → SAM (methylation donor) → Homocysteine", "Homocystinuria: CBS deficiency; B6, B12, folate related"],
        ["Histidine", "His → Histamine; His → Urocanate", "Histidinemia; buffer at pH 7.4"],
        ["Glycine", "Gly → Heme; Gly+Arg→Creatine; bile salt conjugation", "Non-ketotic hyperglycinemia"],
        ["Glutamine", "NH3 transport in blood; TCA anaplerosis", "Major N carrier in blood"],
        ["GABA", "Glu → GABA (GAD, B6 cofactor)", "Inhibitory NT; B6 deficiency → seizures"],
        ["Cysteine", "Homocysteine + Ser → Cys (CBS)", "Homocystinuria: thromboembolism, lens dislocation"],
    ],
    col_widths=[3.5*cm, 7*cm, 6.5*cm]
))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: PKU - Phenylalanine accumulates → phenylpyruvate, phenylacetate, phenyllactate in urine. Diet: restrict Phe (no aspartame!). Screen by Guthrie test.", exam_tip))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 7: NUCLEOTIDE METABOLISM & MOLECULAR BIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 7: NUCLEOTIDE METABOLISM & MOLECULAR BIOLOGY", colors.HexColor("#1A237E")))
story.append(sp())

story.append(Paragraph("Purine & Pyrimidine Synthesis", sec_head))
story.append(two_col_table(
    ["Feature", "Purine Synthesis", "Pyrimidine Synthesis"],
    [
        ["Type", "De novo (ring built on ribose)", "Ring formed first, then added to ribose"],
        ["Rate-limiting enzyme", "PRPP amidotransferase", "CPS-II (cytoplasm) → CAD enzyme"],
        ["First committed product", "IMP (inosine monophosphate)", "UMP"],
        ["Products", "AMP, GMP (from IMP)", "UMP → CTP, TMP"],
        ["Key precursors", "Glycine, Glutamine, Aspartate, CO2, N10-formyl-THF", "Glutamine, CO2, Aspartate"],
        ["Inhibited by", "PRPP amidotransferase by AMP, GMP", "UTP inhibits CPS-II"],
        ["Drug targets", "6-MP, 6-TG, Allopurinol (↓ de novo)", "5-FU, Methotrexate (↓ TMP)"],
        ["Salvage pathway", "HGPRT (Hypoxanthine-Guanine PRTase)", "Thymidine kinase"],
    ],
    col_widths=[4*cm, 6.5*cm, 6.5*cm]
))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: Lesch-Nyhan syndrome = HGPRT deficiency → ↑uric acid + self-mutilation + choreoathetosis + intellectual disability. X-linked recessive.", exam_tip))
story.append(Paragraph("⭐ EXAM TIP: Allopurinol inhibits xanthine oxidase → ↓ uric acid. Also inhibits de novo purine synthesis (↑ PRPP → feedback). Used in gout & tumor lysis syndrome.", exam_tip))
story.append(sp())

story.append(Paragraph("DNA Replication Key Concepts", sec_head))
story.append(info_box("DNA Replication & Repair", [
    "DNA Pol III (prokaryotes) / DNA Pol δ, ε (eukaryotes): main replicating polymerases (5'→3')",
    "DNA Pol I (prokaryotes): removes RNA primers, fills gaps",
    "DNA Pol α: initiates synthesis with RNA primer in eukaryotes",
    "Helicase: unwinds DNA (uses ATP)",
    "Primase: makes RNA primer",
    "Topoisomerase I: relaxes supercoils (nicks 1 strand); Topo II: nicks both strands",
    "Fluoroquinolones target prokaryotic DNA gyrase (Topo II). Eukaryotic Topo II targeted by etoposide",
    "Okazaki fragments: on lagging strand (3'→5' template read, 5'→3' synthesis)",
    "Telomerase: adds TTAGGG repeats; active in germ cells, stem cells, cancer cells",
]))
story.append(sp())

story.append(Paragraph("DNA Repair Mechanisms", sec_head))
story.append(two_col_table(
    ["Repair Type", "Fixes", "Key Enzyme", "Disease if Defective"],
    [
        ["Base Excision Repair (BER)", "Small base changes (deamination, oxidation)", "AP endonuclease, DNA glycosylase", "—"],
        ["Nucleotide Excision Repair (NER)", "Bulky adducts, UV dimers (thymine)", "Endonuclease complex", "Xeroderma pigmentosum"],
        ["Mismatch Repair (MMR)", "Replication errors, mismatches", "MSH2, MLH1", "Lynch syndrome (HNPCC)"],
        ["Homologous Recombination", "DSBs (double strand breaks)", "BRCA1, BRCA2, RAD51", "BRCA-related cancers"],
        ["NHEJ", "DSBs (error-prone)", "Ku proteins, DNA-PKcs", "Radiation sensitivity"],
    ],
    col_widths=[4*cm, 4*cm, 4.5*cm, 4.5*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC DNA repair diseases: <b>"X-ray Lynch's Beautiful Niece"</b> = Xeroderma pigmentosum (NER), Lynch/HNPCC (MMR), BRCA (HR), NHEJ', mnemonic))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 8: VITAMINS
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 8: VITAMINS (FAT & WATER SOLUBLE)", colors.HexColor("#00695C")))
story.append(sp())

story.append(Paragraph("Fat-Soluble Vitamins (A, D, E, K)", sec_head))
story.append(two_col_table(
    ["Vitamin", "Active Form", "Key Functions", "Deficiency", "Toxicity"],
    [
        ["A (Retinol)", "Retinal (vision), Retinoic acid (gene reg.)", "Night vision, epithelial integrity, immunity", "Night blindness, Bitot's spots, xerophthalmia, keratomalacia", "Teratogenic (↑ICP, liver damage)"],
        ["D (Cholecalciferol)", "1,25-(OH)2 D3 (Calcitriol)", "Ca²⁺/PO4 absorption, bone mineralization", "Rickets (children), Osteomalacia (adults), Tetany", "Hypercalcemia, metastatic calcification"],
        ["E (Tocopherol)", "α-Tocopherol", "Antioxidant, protects RBC membrane", "Hemolytic anemia, ataxia, peripheral neuropathy", "Rare; anticoagulant effect"],
        ["K (Phylloquinone)", "Menaquinone", "γ-carboxylation of clotting factors II,VII,IX,X, C,S,Z", "Bleeding, ↑PT/INR; neonatal hemorrhage", "Hemolytic anemia (excess Vit K3)"],
    ],
    col_widths=[2.5*cm, 3.5*cm, 4.5*cm, 4*cm, 2.5*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Fat-soluble vitamins: <b>"ADEK"</b> (Absorbed with Dietary fat, Excess accumulates in body Kills)', mnemonic))
story.append(Paragraph("⭐ EXAM TIP: Vit D synthesis: 7-dehydrocholesterol → (UV skin) → Cholecalciferol → (liver 25-OH) → (kidney 1α-OH) → Calcitriol. CYP27B1 (kidney) is rate-limiting.", exam_tip))
story.append(sp())

story.append(Paragraph("Water-Soluble Vitamins (B complex & C)", sec_head))
story.append(two_col_table(
    ["Vitamin", "Active Form / Role", "Deficiency Syndrome", "Key Mnemonic"],
    [
        ["B1 (Thiamine)", "TPP → PDH, α-KG dehy., Transketolase", "Wernicke's (confusion, ataxia, ophtha), Korsakoff's, Beri-beri (wet=cardiac, dry=neuro)", "B1 = BeriBeri"],
        ["B2 (Riboflavin)", "FAD, FMN → oxidation-reduction", "Cheilosis, angular stomatitis, corneal vascularization, magenta tongue", "2 lips (cheilosis)"],
        ["B3 (Niacin)", "NAD+, NADP+ → redox reactions", "Pellagra: 4 Ds = Dermatitis, Diarrhea, Dementia, Death", "B3 = 3 Ds (Pellagra)"],
        ["B5 (Pantothenate)", "CoA → FA synthesis, TCA", "Burning feet syndrome", "Panto=everywhere"],
        ["B6 (Pyridoxine)", "PLP → transamination, decarboxylation, GABA synth.", "Sideroblastic anemia, peripheral neuropathy, cheilosis; INH toxicity", "B6 = transamination"],
        ["B7 (Biotin)", "Carboxylation reactions (ACC, PC, MCC, PCC)", "Alopecia, dermatitis, depression; raw egg white (avidin)", "B7 = Biotin, CO2 carrier"],
        ["B9 (Folate)", "THF → 1-carbon transfers; dTMP synthesis", "Megaloblastic anemia (MCV↑, hypersegmented neutrophils); NTD", "Folate = Fetus (NTD)"],
        ["B12 (Cobalamin)", "Methylcobalamin, Adenosylcobalamin", "Megaloblastic anemia + subacute combined degeneration (SACD)", "B12 = SACD (spinal cord)"],
        ["C (Ascorbic acid)", "Hydroxylation of Pro & Lys (collagen); antioxidant", "Scurvy: perifollicular hemorrhage, corkscrew hair, gum bleeding, poor wound healing", "C = Collagen"],
    ],
    col_widths=[3*cm, 5*cm, 5.5*cm, 3.5*cm]
))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: B12 & Folate both cause megaloblastic anemia BUT only B12 deficiency causes neurological signs (SACD - demyelination of posterior and lateral columns).", exam_tip))
story.append(Paragraph("⭐ EXAM TIP: Folate trap: in B12 deficiency, THF is trapped as methyl-THF (cannot donate its methyl group) → functional folate deficiency even with normal folate levels.", exam_tip))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 9: MINERALS & TRACE ELEMENTS
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 9: MINERALS & TRACE ELEMENTS", colors.HexColor("#BF360C")))
story.append(sp())

story.append(two_col_table(
    ["Mineral", "Key Role", "Deficiency", "Excess/Toxicity"],
    [
        ["Iron (Fe)", "Heme synthesis, electron transport (cytochromes), ribonucleotide reductase", "IDA: microcytic hypochromic anemia, koilonychia, Plummer-Vinson", "Hemochromatosis: liver cirrhosis, diabetes, bronzing skin, cardiomyopathy"],
        ["Copper (Cu)", "Cytochrome c oxidase, Lysyl oxidase, Ceruloplasmin, Tyrosinase, Dopamine β-hydroxylase, SOD", "Menkes disease: X-linked, kinky hair, neurodegeneration, ↓ ceruloplasmin", "Wilson disease: liver, CNS, Kayser-Fleischer rings; ↓ ceruloplasmin"],
        ["Zinc (Zn)", "100+ enzyme cofactor, wound healing, taste, smell, immune", "Growth retardation, hypogonadism, poor wound healing, alopecia, acrodermatitis enteropathica", "Nausea, copper deficiency"],
        ["Selenium (Se)", "Glutathione peroxidase (antioxidant), Thyroxine deiodinase", "Keshan disease (cardiomyopathy), Kashin-Beck disease", "Selenosis"],
        ["Iodine (I)", "Thyroid hormone synthesis (T3/T4)", "Goiter, Cretinism (congenital hypothyroidism)", "Wolff-Chaikoff effect (transient hypothyroidism)"],
        ["Fluoride (F)", "Hydroxyapatite → fluorapatite (tooth & bone)", "Dental caries", "Fluorosis: mottled teeth, skeletal fluorosis"],
        ["Chromium (Cr)", "Potentiates insulin action (GTF)", "Impaired glucose tolerance, neuropathy", "Hexavalent Cr: carcinogenic (lung)"],
        ["Manganese (Mn)", "Mitochondrial SOD, Arginase", "Poor growth, bone abnormalities", "Manganism (Parkinson-like)"],
    ],
    col_widths=[3*cm, 5*cm, 5*cm, 4*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Copper enzymes: <b>"COLTS Drink Malt"</b> = Cytochrome c Oxidase, Lysyl Oxidase, Tyrosinase, SOD, Dopamine β-hydroxylase, ceruloplasMin', mnemonic))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 10: HEMOGLOBIN & PORPHYRINS
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 10: HEMOGLOBIN & PORPHYRIN METABOLISM", colors.HexColor("#880E4F")))
story.append(sp())

story.append(Paragraph("Hemoglobin Structure & Variants", sec_head))
story.append(two_col_table(
    ["Hb Variant", "Structure / Mutation", "Features"],
    [
        ["HbA (adult)", "2α + 2β", "Normal adult Hb (>95%)"],
        ["HbA2", "2α + 2δ", "~2.5%; ↑ in β-thalassemia trait"],
        ["HbF (fetal)", "2α + 2γ", "Higher O2 affinity; ↑ in sickle cell (protective)"],
        ["HbS (sickle)", "β6: Glu→Val (GAG→GTG)", "Sickling in low O2; vaso-occlusion, hemolysis"],
        ["HbC", "β6: Glu→Lys", "Target cells; mild hemolysis"],
        ["HbH", "β4 tetramers", "α-thalassemia (3 gene deletion)"],
        ["Hb Barts", "γ4 tetramers", "α-thalassemia (4 gene deletion); hydrops fetalis"],
        ["MetHb", "Fe³⁺ (oxidized)", "Cannot carry O2; treat with methylene blue (G6PD intact) or ascorbic acid"],
        ["CO-Hb", "CO bound to Fe²⁺", "CO poisoning; cherry red appearance; ↑ O2 affinity (left shift)"],
    ],
    col_widths=[3*cm, 5*cm, 9*cm]
))
story.append(sp())
story.append(Paragraph("Oxygen Dissociation Curve Shifts", sec_head))
story.append(info_box("O2 Dissociation Curve", [
    "RIGHT SHIFT (↓ O2 affinity = more O2 released to tissues):",
    "  → ↑ Temperature, ↑ CO2 (Bohr effect), ↑ H+ (acidosis), ↑ 2,3-BPG",
    "  → Exercise, fever, high altitude (chronic) — tissues need more O2",
    "LEFT SHIFT (↑ O2 affinity = less O2 released):",
    "  → ↓ Temperature, ↓ CO2, ↓ H+ (alkalosis), ↓ 2,3-BPG",
    "  → HbF, CO poisoning, MetHb, stored blood",
    "🧠 Mnemonic RIGHT shift = 'CADET, face RIGHT!' = CO2, Altitude (chronic), DPG, Exercise, Temperature",
], bg=RED_LIGHT, title_color=RED))
story.append(sp())

story.append(Paragraph("Heme Synthesis & Porphyrias", sec_head))
story.append(two_col_table(
    ["Step / Enzyme", "Location", "Porphyria / Disorder if Defective"],
    [
        ["ALA synthase (rate-limiting)", "Mitochondria", "Induced by drugs (CYP450 inducers), heme inhibits"],
        ["ALA dehydratase", "Cytoplasm", "Inhibited by LEAD (Pb) → ↑ALA in urine"],
        ["Porphobilinogen deaminase", "Cytoplasm", "AIP (Acute Intermittent Porphyria): abd pain, neuropsych, NO skin findings; ↑ALA, ↑PBG"],
        ["Uroporphyrinogen III synthase", "Cytoplasm", "Congenital erythropoietic porphyria"],
        ["Uroporphyrinogen decarboxylase", "Cytoplasm", "Porphyria cutanea tarda: most COMMON porphyria; photosensitivity, blisters"],
        ["Ferrochelatase", "Mitochondria", "Inhibited by Pb; EPP (Erythropoietic protoporphyria)"],
    ],
    col_widths=[5.5*cm, 3*cm, 8.5*cm]
))
story.append(sp())
story.append(Paragraph("⭐ EXAM TIP: Lead poisoning inhibits ALA dehydratase AND ferrochelatase → ↑ALA, ↑protoporphyrin IX, ↓heme. Basophilic stippling in RBCs. Treatment: EDTA, BAL, DMSA.", exam_tip))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 11: MOLECULAR BIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 11: MOLECULAR BIOLOGY & GENETICS", colors.HexColor("#1A237E")))
story.append(sp())

story.append(Paragraph("Transcription & Translation", sec_head))
story.append(two_col_table(
    ["Process", "Key Feature", "Inhibitors (drugs/toxins)"],
    [
        ["Transcription (DNA→RNA)", "RNA Pol II → mRNA; no primer needed; template is 3'→5'", "Rifampin (prokaryotic RNA Pol); Actinomycin D (intercalates, both)"],
        ["mRNA Processing", "5' cap (7-methyl G), 3' poly-A tail, splicing by snRNPs", "—"],
        ["Translation (RNA→Protein)", "Ribosome 80S (euk), 70S (prok); starts AUG (Met)", "See table below"],
        ["Aminoacyl-tRNA synthetase", "Charges tRNA with correct AA (uses ATP→AMP)", "High fidelity step"],
        ["Peptidyl transferase", "Catalyzes peptide bond (rRNA, ribozyme)", "Chloramphenicol (50S, prok); Linezolid (50S, prok)"],
    ],
    col_widths=[4*cm, 7*cm, 6*cm]
))
story.append(sp())

story.append(Paragraph("Antibiotic Sites of Action (Protein Synthesis)", sec_head))
story.append(two_col_table(
    ["Antibiotic", "Target", "Effect"],
    [
        ["Aminoglycosides (Gentamicin)", "30S (prokaryote)", "Misreading of mRNA; bactericidal"],
        ["Tetracyclines", "30S (prokaryote)", "Block aminoacyl-tRNA binding; bacteriostatic"],
        ["Chloramphenicol", "50S - peptidyl transferase", "Bacteriostatic; aplastic anemia (rare)"],
        ["Macrolides (Erythromycin)", "50S - translocation (EF-G)", "Bacteriostatic; GI side effects"],
        ["Linezolid", "50S - prevents 70S formation", "Bacteriostatic; serotonin syndrome risk"],
        ["Fusidic acid", "EF-G (elongation factor)", "Bacteriostatic; topical/systemic staph"],
        ["Diphtheria toxin", "EF-2 (eukaryotic!)", "ADP-ribosylation → halts translation; FATAL"],
        ["Ricin", "28S rRNA (eukaryotic 60S)", "Depurination; extremely toxic"],
        ["Cycloheximide", "60S (eukaryotic)", "Blocks translocation; research tool"],
    ],
    col_widths=[5*cm, 5.5*cm, 6.5*cm]
))
story.append(sp())

story.append(Paragraph("Gene Regulation & Oncogenes", sec_head))
story.append(info_box("Key Oncogenes & Tumor Suppressors", [
    "RAS: Most commonly mutated oncogene; GTPase; mutated in 30% of all cancers",
    "MYC: Transcription factor; Burkitt lymphoma (t8;14), neuroblastoma (N-MYC)",
    "HER2/neu (ERBB2): Receptor tyrosine kinase; amplified in breast/gastric cancer; target of Trastuzumab",
    "BCR-ABL: t(9;22) Philadelphia chromosome; CML; target of Imatinib (Gleevec)",
    "RET: Thyroid cancer (MEN 2A/2B), papillary thyroid carcinoma",
    "p53 (TP53): Guardian of genome; most commonly mutated tumor suppressor; Li-Fraumeni syndrome",
    "RB1: Retinoblastoma; first tumor suppressor described; 2-hit hypothesis (Knudson)",
    "BRCA1/2: Breast/ovarian cancer; HR repair",
    "APC: Colorectal cancer (FAP); WNT signaling",
    "VHL: Renal cell carcinoma; HIF regulation; clear cell RCC",
]))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 12: INBORN ERRORS OF METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 12: INBORN ERRORS OF METABOLISM", colors.HexColor("#E65100")))
story.append(sp())

story.append(Paragraph("Lysosomal Storage Diseases", sec_head))
story.append(two_col_table(
    ["Disease", "Enzyme Deficient", "Accumulated Substrate", "Features"],
    [
        ["Gaucher (MC LSD)", "β-Glucocerebrosidase", "Glucocerebroside", "Gaucher cells (crumpled tissue paper), splenomegaly, bone pain; Type 1 (no CNS)"],
        ["Niemann-Pick", "Sphingomyelinase", "Sphingomyelin", "Cherry red macula, sea-blue histiocytes, CNS degeneration; Types A/B/C"],
        ["Tay-Sachs", "Hexosaminidase A", "GM2 ganglioside", "Cherry red macula, NO hepatosplenomegaly, Ashkenazi Jews; fatal by age 4"],
        ["Fabry", "α-Galactosidase A", "Globotriaosylceramide", "X-linked; angiokeratomas, peripheral neuropathy, renal failure, corneal deposits"],
        ["Krabbe", "Galactocerebrosidase", "Galactocerebroside", "Globoid cells, peripheral neuropathy, early death"],
        ["Metachromatic leuko", "Arylsulfatase A", "Cerebroside sulfate", "Demyelination, metachromatic granules"],
        ["Hurler (MPS-I)", "α-L-Iduronidase", "Heparan/Dermatan sulfate", "Gargoylism, corneal clouding, AR, severe"],
        ["Hunter (MPS-II)", "Iduronate sulfatase", "Heparan/Dermatan sulfate", "X-linked, NO corneal clouding, aggressive behavior"],
        ["Pompe (GSD-II)", "Acid maltase (α-1,4-glucosidase)", "Glycogen", "Cardiomegaly, hypotonia; ONLY GSD that is a LSD"],
    ],
    col_widths=[3.5*cm, 4*cm, 4*cm, 5.5*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC LSDs with Cherry Red Macula: <b>"Tay-Sachs, Niemann-Pick, Sandhoff, Sialidosis"</b> (TNS+S)', mnemonic))
story.append(Paragraph("⭐ EXAM TIP: Cherry red spot = fovea appears red because surrounding macular ganglion cells are white/pale due to lipid accumulation.", exam_tip))
story.append(sp())

story.append(Paragraph("Amino Acid & Other IEM", sec_head))
story.append(two_col_table(
    ["Disease", "Enzyme / Gene", "Key Features"],
    [
        ["PKU", "PAH (phenylalanine hydroxylase)", "Musty/mousy odor, fair skin/hair, intellectual disability; screen Guthrie test"],
        ["Maple Syrup Urine Disease", "BCKD (branched-chain α-keto acid dehydrogenase)", "Leucine, Isoleucine, Valine ↑; sweet urine; severe CNS; thiamine helps"],
        ["Homocystinuria", "CBS (cystathionine β-synthase)", "Tall, lens dislocation (upward-out), marfanoid, thromboembolism, intellectual disability"],
        ["Alkaptonuria", "Homogentisate oxidase", "Ochronosis (dark pigment), arthritis, dark urine on standing; benign"],
        ["Albinism (Tyrosinase def)", "Tyrosinase", "No melanin; ↑ risk UV skin cancer; Hermansky-Pudlak (+ bleeding)"],
        ["Hartnup Disease", "Neutral AA transporter (SLC6A19)", "Pellagra-like (tryptophan malabsorption → ↓niacin), cerebellar ataxia"],
        ["Galactosemia (Classic)", "GALT (Gal-1-P uridylyltransferase)", "Jaundice, cataracts, liver failure, E. coli sepsis in neonates; galactose-free diet"],
        ["Galactosemia (Galactokinase def)", "Galactokinase", "Cataracts ONLY; galactitol accumulation"],
        ["Fructose intolerance", "Aldolase B", "Fasting hypoglycemia after fructose; liver/kidney damage; avoid fructose & sucrose"],
        ["Methylmalonic acidemia", "Methylmalonyl-CoA mutase (B12 dep.)", "Acidemia, hyperammonemia; B12 treatment helps some"],
    ],
    col_widths=[4*cm, 5*cm, 8*cm]
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 13: CLINICAL BIOCHEMISTRY & LAB VALUES
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 13: CLINICAL BIOCHEMISTRY & IMPORTANT LAB VALUES", colors.HexColor("#00695C")))
story.append(sp())

story.append(Paragraph("Acid-Base Disorders", sec_head))
story.append(two_col_table(
    ["Disorder", "pH", "PCO2", "HCO3-", "Compensation", "Common Cause"],
    [
        ["Metabolic Acidosis", "↓", "↓ (comp)", "↓ (primary)", "↑RR (Kussmaul resp)", "DKA, lactic acidosis, diarrhea, renal failure"],
        ["Metabolic Alkalosis", "↑", "↑ (comp)", "↑ (primary)", "↓RR (hypoventilation)", "Vomiting, diuretics, Conn's syndrome"],
        ["Respiratory Acidosis", "↓", "↑ (primary)", "↑ (comp)", "↑HCO3- retention (kidney)", "COPD, hypoventilation, narcotic OD"],
        ["Respiratory Alkalosis", "↑", "↓ (primary)", "↓ (comp)", "↓HCO3- excretion (kidney)", "Anxiety, altitude, salicylate OD (early)"],
    ],
    col_widths=[4*cm, 1.5*cm, 2*cm, 2.5*cm, 4*cm, 4*cm]
))
story.append(sp())
story.append(Paragraph("Anion Gap = Na - (Cl + HCO3) | Normal = 8-12 mEq/L", keypoint))
story.append(Paragraph('🧠 MNEMONIC High AG acidosis: <b>"MUDPILES"</b> = Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethanol/Ethylene glycol, Salicylates', mnemonic))
story.append(sp())

story.append(Paragraph("Bilirubin Metabolism", sec_head))
story.append(info_box("Bilirubin Key Points", [
    "Unconjugated (indirect) bilirubin: fat-soluble, NOT excreted in urine, bound to albumin",
    "Conjugated (direct) bilirubin: water-soluble, excreted in urine (dark urine = obstructive jaundice)",
    "Conjugation: in liver by UDP-glucuronosyltransferase (UGT1A1)",
    "Neonatal jaundice: UGT1A1 immature → unconjugated hyperbilirubinemia; treat with phototherapy",
    "Gilbert syndrome: ↓ UGT1A1 activity → benign unconjugated hyperbilirubinemia",
    "Crigler-Najjar type I: absent UGT1A1 → fatal; type II: ↓ activity → responds to phenobarbital",
    "Dubin-Johnson: ↓ conjugated bilirubin transport (MRP2); black liver; benign",
    "Rotor syndrome: similar to DJ but NO black liver, NO melanin",
    "Hemolytic jaundice: ↑indirect; Hepatocellular: ↑both; Obstructive: ↑direct",
]))
story.append(sp())

story.append(Paragraph("Tumor Markers", sec_head))
story.append(two_col_table(
    ["Marker", "Cancer", "Notes"],
    [
        ["AFP (α-fetoprotein)", "HCC, Yolk sac tumor (testis)", "Also elevated in ataxia-telangiectasia; ↓in Down syndrome (prenatal)"],
        ["CEA", "Colorectal, pancreatic, gastric", "Not specific; used for monitoring, not screening"],
        ["PSA", "Prostate cancer", "BPH also raises PSA; most sensitive for prostate"],
        ["CA-125", "Ovarian cancer", "Monitoring; ↑ in endometriosis also"],
        ["CA 19-9", "Pancreatic cancer", "Also in cholangiocarcinoma"],
        ["β-hCG", "Choriocarcinoma, Testicular (non-seminoma)", "Also used in pregnancy testing"],
        ["LDH", "Lymphoma, testicular, any rapid tumor", "Non-specific; reflects tumor burden"],
        ["Calcitonin", "Medullary thyroid carcinoma", "Screens family members in MEN 2A/2B"],
        ["Chromogranin A", "Neuroendocrine tumors (carcinoid, pheochromocytoma)", "Best NET marker"],
    ],
    col_widths=[4*cm, 5*cm, 8*cm]
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 14: HORMONES & SIGNAL TRANSDUCTION
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 14: HORMONES & SIGNAL TRANSDUCTION", colors.HexColor("#4527A0")))
story.append(sp())

story.append(Paragraph("Second Messenger Systems", sec_head))
story.append(two_col_table(
    ["Pathway", "Mechanism", "Hormones/Examples"],
    [
        ["cAMP pathway (Gs)", "Adenylyl cyclase → ↑cAMP → PKA activation", "Glucagon, Epinephrine (β), LH, FSH, TSH, PTH, ACTH, Calcitonin, Secretin, Cholera toxin (locks Gs ON)"],
        ["cAMP pathway (Gi)", "↓Adenylyl cyclase → ↓cAMP", "Somatostatin, α2-adrenergic, Opioids, M2-muscarinic, Pertussis toxin (locks Gi OFF)"],
        ["IP3/DAG (Gq)", "PLC → IP3 (↑Ca²⁺) + DAG (PKC)", "Oxytocin, ADH (V1), GnRH, TRH, Angiotensin II, Histamine (H1), α1-adrenergic"],
        ["Receptor Tyrosine Kinase", "Dimerization → autophosphorylation → cascade", "Insulin, IGF-1, EGF, PDGF, FGF, VEGF"],
        ["JAK-STAT pathway", "JAK → STAT phosphorylation → transcription", "GH, Prolactin, Erythropoietin, Cytokines (IL, IFN)"],
        ["Nuclear receptor (intracellular)", "Ligand-receptor → DNA binding → gene expression", "Steroid hormones, T3/T4, Vitamin D, Retinoic acid"],
    ],
    col_widths=[4*cm, 5.5*cm, 7.5*cm]
))
story.append(sp())
story.append(Paragraph('🧠 MNEMONIC Gq-coupled: <b>"GOAT MAH"</b> = GnRH, Oxytocin, ADH(V1), TRH, M1/M3-mAChR, Angiotensin II, H1-histamine', mnemonic))
story.append(Paragraph("⭐ EXAM TIP: Cholera toxin → ADP-ribosylates Gs (keeps it ON) → ↑cAMP in intestinal cells → ↑Cl- secretion → rice-water diarrhea.", exam_tip))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# CHAPTER 15: MASTER MNEMONICS & QUICK REFERENCE
# ══════════════════════════════════════════════════════════════════════════════
story.append(chapter_banner("CHAPTER 15: MASTER MNEMONICS & QUICK REFERENCE", colors.HexColor("#880E4F")))
story.append(sp())

story.append(Paragraph("Top NEET PG Biochemistry Mnemonics", sec_head))
mnemonics_list = [
    ("Essential Amino Acids", '"PVT TIM HaLL" = Phe, Val, Thr, Trp, Ile, Met, His, Arg(semi), Leu, Lys'),
    ("Only Ketogenic AAs", '"Leu & Lys ONLY" — neither enters gluconeogenesis'),
    ("Both Gluco+Keto AAs", '"IFTYT" = Ile, Phe, Thr, Tyr, Trp'),
    ("PDH Cofactors", '"Tender Loving Care For Nancy" = TPP, Lipoate, CoA, FAD, NAD+'),
    ("Fat Soluble Vitamins", '"ADEK" — Absorbed with Dietary fat, Excess can Kill'),
    ("Pellagra (B3 deficiency)", '"3Ds + D" = Dermatitis, Diarrhea, Dementia, Death'),
    ("Urea cycle order", '"Ordinarily Careless Crappers Are Also Arrogant Urologists" = Ornithine→Citrulline→Carbamoyl-P→Arginosuccinate→Arginine→Urea'),
    ("High Anion Gap Acidosis", '"MUDPILES" = Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactate, EtOH/Ethylene glycol, Salicylates'),
    ("O2 curve RIGHT shift", '"CADET face RIGHT!" = CO2↑, Altitude (chronic), DPG↑, Exercise, Temp↑'),
    ("Lipoprotein density order", '"Chunky Villagers Ignore Large Healthy People" = Chylomicron→VLDL→IDL→LDL→HDL'),
    ("Copper enzymes", '"COLTS Drink Malt" = Cytochrome oxidase, Lysyl oxidase, Tyrosinase, SOD, Dopamine-β-hydroxylase, Melanin/ceruloplasmin'),
    ("Lysosomal storage: Cherry red macula", '"TNS²" = Tay-Sachs, Niemann-Pick, Sandhoff, Sialidosis'),
    ("Glycogen storage diseases", '"Very Poor Carbo Makes Arnold His Trainer" = Von Gierke, Pompe, Cori, Mc Ardle, Anderson, Hers, Tarui'),
    ("Vitamins requiring B6 (PLP)", '"AGATE" = ALT/AST (aminotransferases), GABA synthesis, ALA synthase, Tryptophan→serotonin, cystathionine'),
    ("Gq-coupled receptors", '"GOAT MAH" = GnRH, Oxytocin, ADH(V1), TRH, M1/M3-mAChR, Ang II, H1'),
    ("DNA repair disorders", '"X-ray Lynch Beautiful Niece" = Xeroderma pig (NER), Lynch/HNPCC (MMR), BRCA (HR), NHEJ'),
    ("Gluconeogenesis substrates", '"GOAL" = Glycerol, Odd-chain FA, Amino acids (glucogenic), Lactate'),
    ("Heme synthesis inhibited by Pb", '"Pb blocks ALA dehydratase & Ferrochelatase → ↑ALA, ↑Protoporphyrin, ↓Heme"'),
    ("MEN syndromes", '"MEN 1: 3Ps = Pituitary, Parathyroid, Pancreas | MEN 2A: MTC + Pheo + Hyperparathyroid | MEN 2B: MTC + Pheo + Marfanoid + Mucosal neuromas"'),
    ("Inborn errors of AA metabolism", '"PKU = musty, MSUD = maple syrup, IVA = sweaty feet, Isovaleric = cheesy odor"'),
]
for name, content in mnemonics_list:
    story.append(Paragraph(f"<b>{name}:</b>  {content}", mnemonic))
    story.append(spm())

story.append(sp())
story.append(hr(RED))
story.append(sp())

story.append(Paragraph("Recent NEET PG High-Frequency Topics (2022-2025)", sec_head))
story.append(info_box("Most Commonly Asked Topics", [
    "1. Enzyme kinetics: Km/Vmax interpretation, competitive vs non-competitive inhibition",
    "2. Glycogen storage diseases (especially Pompe, Von Gierke, McArdle)",
    "3. Lysosomal storage diseases (Gaucher, Tay-Sachs, Niemann-Pick, Fabry)",
    "4. Vitamin deficiencies and their specific clinical features",
    "5. Hemoglobin variants, O2 dissociation curve shifts",
    "6. Lead poisoning and porphyrias (AIP vs PCT)",
    "7. PKU, Homocystinuria, Alkaptonuria, MSUD (inborn errors)",
    "8. Urea cycle disorders and hyperammonemia",
    "9. Cholesterol/lipoprotein disorders and drug targets (statins, fibrates)",
    "10. DNA repair mechanisms and associated syndromes",
    "11. Oncogenes/tumor suppressors (RAS, p53, RB1, BCR-ABL, BRCA)",
    "12. Bilirubin metabolism and jaundice types",
    "13. HMP shunt (G6PD deficiency)",
    "14. Signal transduction pathways (cAMP, IP3/DAG, RTK, JAK-STAT)",
    "15. Collagen structure, types, and disorders (Scurvy, EDS, OI)",
], bg=YELLOW_LIGHT, title_color=YELLOW))
story.append(sp())

story.append(Paragraph("Mind Map: NEET PG Biochemistry at a Glance", sec_head))
story.append(mind_map_box("BIOCHEMISTRY NEET PG", {
    "Proteins": ["AA classification", "pI/pKa", "Collagen (Gly-Pro-Hyp)", "Hb variants"],
    "Carbohydrates": ["Glycolysis (PFK-1 R.L.)", "TCA (Isocitrate dehy R.L.)", "HMP (G6PD)", "GSD (Pompe=LSD)"],
    "Lipids": ["FA synthesis (ACC R.L.)", "β-oxidation (CPT-I gate)", "Ketones (liver only)", "Cholesterol (HMG-CoA R)"],
    "Vitamins": ["A=night blindness", "D=Rickets/Osteomalacia", "B1=Wernicke/Beri-beri", "B12=SACD+megaloblastic"],
    "IEM": ["PKU (musty)", "MSUD (maple syrup)", "Gaucher (MC LSD)", "Tay-Sachs (cherry red)"],
    "Molecular Bio": ["p53 guardian", "RAS most common oncogene", "BRCA=HR repair", "Lynch=MMR defect"],
    "Clinical": ["DKA=anion gap acidosis", "Lead→ALA dehy↓", "Porphyria PCT=most common", "Bilirubin=UGT1A1"],
}))
story.append(sp())

story.append(Paragraph("⚡ LAST MINUTE POWER FACTS", sec_head))
facts = [
    "Rate-limiting enzymes: Glycolysis=PFK-1, TCA=Isocitrate dehydrogenase, FA synthesis=ACC, Cholesterol=HMG-CoA reductase, Urea cycle=CPS-I, HMP=G6PD, Heme=ALA synthase",
    "Only tissues with G6Pase (can release glucose): LIVER, KIDNEY, SMALL INTESTINE (NOT muscle, NOT brain)",
    "Transamination requires B6 (PLP); Carboxylation requires Biotin; Hydroxylation requires Vit C; Methylation requires B12/Folate",
    "Night blindness is FIRST sign of Vitamin A deficiency",
    "Vitamin K factors: II, VII, IX, X, Protein C, S, Z (Clotting factors 2+7+9+10=prothrombin time affected)",
    "Most common porphyria: PCT (Porphyria cutanea tarda); Most common acute porphyria: AIP",
    "Zellweger syndrome: peroxisome biogenesis disorder; very long chain FA ↑; no peroxisomes",
    "Refsum disease: phytanic acid accumulation (peroxisomal α-oxidation defect)",
    "Methionine is the only AA that initiates protein synthesis (codes for Met/formyl-Met)",
    "Selenocysteine = 21st amino acid (encoded by UGA stop codon, requires SECIS element)",
]
for i, fact in enumerate(facts, 1):
    story.append(Paragraph(f"<b>{i}.</b> {fact}", bullet))
    story.append(spm())

story.append(sp())
story.append(hr(DARK_BLUE))
story.append(sp())
story.append(Paragraph("BEST OF LUCK FOR NEET PG! 🎯", S("Footer", fontSize=14, fontName="Helvetica-Bold",
             textColor=DARK_BLUE, alignment=TA_CENTER)))
story.append(Paragraph("Prepared from Lippincott Biochemistry, Harper's Illustrated Biochemistry & Standard PG References", 
             S("Src", fontSize=8, fontName="Helvetica-Oblique", textColor=colors.grey, alignment=TA_CENTER)))

# ── Build PDF ──────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=1.5*cm,
    leftMargin=1.5*cm,
    topMargin=1.5*cm,
    bottomMargin=1.5*cm,
    title="NEET PG Biochemistry Rapid Revision",
    author="Orris Medical",
)

def add_page_number(canvas, doc):
    canvas.saveState()
    if doc.page > 1:
        canvas.setFont("Helvetica", 8)
        canvas.setFillColor(colors.grey)
        canvas.drawRightString(A4[0] - 1.5*cm, 0.8*cm, f"Page {doc.page}  |  NEET PG Biochemistry Rapid Revision")
        canvas.drawString(1.5*cm, 0.8*cm, "Orris Medical")
    canvas.restoreState()

doc.build(story, onFirstPage=add_page_number, onLaterPages=add_page_number)
print(f"PDF created: {OUTPUT}")

Error: String not found in file: '        col_widths=[2cm, 3cm, 5*cm, 7*cm]'

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