Biochemistry Pathways & Cycles - Short Understanding Guide

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

OUTPUT = "/home/daytona/workspace/biochem-flashcards/Biochemistry_Flashcards.pdf"

# ── colour palette ──────────────────────────────────────────────
C_NAVY      = colors.HexColor("#1A2F5A")
C_BLUE      = colors.HexColor("#2E5BA8")
C_LIGHT     = colors.HexColor("#EAF0FB")
C_ACCENT    = colors.HexColor("#F4A623")
C_GREEN     = colors.HexColor("#27AE60")
C_GREEN_LT  = colors.HexColor("#E8F8F0")
C_RED       = colors.HexColor("#C0392B")
C_RED_LT    = colors.HexColor("#FEF0EE")
C_PURPLE    = colors.HexColor("#6C3483")
C_PURPLE_LT = colors.HexColor("#F4EEF9")
C_ORANGE    = colors.HexColor("#D35400")
C_ORANGE_LT = colors.HexColor("#FEF5EC")
C_TEAL      = colors.HexColor("#117A65")
C_TEAL_LT   = colors.HexColor("#E8F6F3")
C_GRAY_LT   = colors.HexColor("#F7F9FC")
C_WHITE     = colors.white
C_BLACK     = colors.HexColor("#1A1A2E")

# category colours: (header_bg, card_bg)
CAT_COLOURS = {
    "Glycolysis":               (C_BLUE,   C_LIGHT),
    "TCA Cycle":                (C_GREEN,  C_GREEN_LT),
    "Oxidative Phosphorylation":(C_NAVY,   C_GRAY_LT),
    "Gluconeogenesis":          (C_RED,    C_RED_LT),
    "Glycogen Metabolism":      (C_PURPLE, C_PURPLE_LT),
    "Beta-Oxidation":           (C_ORANGE, C_ORANGE_LT),
    "Fatty Acid Synthesis":     (C_TEAL,   C_TEAL_LT),
    "Urea Cycle":               (C_RED,    C_RED_LT),
    "Pentose Phosphate Pathway":(C_GREEN,  C_GREEN_LT),
    "Ketone Body Metabolism":   (C_ORANGE, C_ORANGE_LT),
}

# ── flashcard data ───────────────────────────────────────────────
# Each card: (category, front_question, back_answer)
CARDS = [
    # ── GLYCOLYSIS ──────────────────────────────────────────────
    ("Glycolysis",
     "What is the fate of Glucose-6-Phosphate (G6P)?",
     "Three possible fates:\n"
     "1. Continue glycolysis → Fructose-6-P\n"
     "2. Glycogenesis → stored as glycogen\n"
     "3. Pentose phosphate pathway → NADPH + ribose-5-P\n\n"
     "Key: G6P is the first committed intermediate; cannot exit most cells (no G6Pase except liver/kidney/intestine)."),

    ("Glycolysis",
     "What is the fate of Fructose-1,6-Bisphosphate (F-1,6-BP)?",
     "Cleaved by aldolase into two 3-carbon triose phosphates:\n"
     "• DHAP (dihydroxyacetone phosphate)\n"
     "• Glyceraldehyde-3-phosphate (G3P)\n\n"
     "DHAP → G3P (by triose phosphate isomerase)\n"
     "Both G3P molecules feed into ATP-generating phase."),

    ("Glycolysis",
     "What is the fate of Pyruvate (the end product of glycolysis)?",
     "FOUR possible fates depending on conditions:\n"
     "1. With O₂ → Acetyl-CoA (pyruvate dehydrogenase) → TCA cycle\n"
     "2. Without O₂ → Lactate (LDH; regenerates NAD⁺)\n"
     "3. Gluconeogenesis → Oxaloacetate (pyruvate carboxylase, liver)\n"
     "4. Transamination → Alanine (nitrogen transport from muscle)\n\n"
     "Key enzyme: Pyruvate dehydrogenase (PDH) — irreversible, requires B1/B2/B3/B5/lipoic acid."),

    ("Glycolysis",
     "What is the fate of DHAP (Dihydroxyacetone Phosphate)?",
     "Three fates:\n"
     "1. → G3P via triose phosphate isomerase (continues glycolysis)\n"
     "2. → Glycerol-3-P → triacylglycerol synthesis (fat storage)\n"
     "3. → Glycerol-3-P → glycerophospholipid synthesis\n\n"
     "DHAP is the entry point for glycerol into both glycolysis and lipid synthesis."),

    ("Glycolysis",
     "What is the fate of 1,3-Bisphosphoglycerate (1,3-BPG)?",
     "Two fates:\n"
     "1. → 3-Phosphoglycerate + ATP (via phosphoglycerate kinase)\n"
     "   — substrate-level phosphorylation\n"
     "2. → 2,3-BPG (in RBCs, via bisphosphoglycerate mutase)\n"
     "   — 2,3-BPG allosterically reduces Hb-O₂ affinity → O₂ delivery to tissues"),

    ("Glycolysis",
     "What is the fate of Phosphoenolpyruvate (PEP)?",
     "Two fates:\n"
     "1. → Pyruvate + ATP (via pyruvate kinase) — glycolysis continues\n"
     "2. ← OAA (via PEPCK) — gluconeogenesis\n\n"
     "PEP is the highest-energy phosphate compound in glycolysis.\n"
     "Pyruvate kinase is inhibited by ATP and alanine (fed state signals)."),

    # ── TCA CYCLE ────────────────────────────────────────────────
    ("TCA Cycle",
     "What is the fate of Acetyl-CoA entering the TCA cycle?",
     "Condenses with Oxaloacetate (4C) → Citrate (6C)\n"
     "Enzyme: Citrate synthase\n\n"
     "Per turn, acetyl-CoA carbons are NOT directly released as CO₂;\n"
     "they become part of OAA in subsequent turns.\n\n"
     "Acetyl-CoA can also:\n"
     "→ FA synthesis (via citrate export to cytosol)\n"
     "→ Ketone body synthesis (if OAA is limiting)"),

    ("TCA Cycle",
     "What is the fate of Citrate (6C)?",
     "In mitochondria: → Isocitrate (aconitase)\n"
     "In cytosol (exported via citrate shuttle):\n"
     "→ Acetyl-CoA + OAA (by citrate lyase)\n"
     "→ Acetyl-CoA feeds fatty acid synthesis\n"
     "→ OAA feeds back or → NADPH via malic enzyme\n\n"
     "Citrate is an allosteric inhibitor of PFK-1 (slows glycolysis when TCA is full)."),

    ("TCA Cycle",
     "What is the fate of Isocitrate (6C)?",
     "→ α-Ketoglutarate (5C) + CO₂\n"
     "Enzyme: Isocitrate dehydrogenase (IDH)\n"
     "Cofactor: NAD⁺ → NADH produced\n\n"
     "This is the first CO₂-releasing step and a major\n"
     "regulatory point of the TCA cycle.\n"
     "IDH is activated by ADP/Ca²⁺ and inhibited by ATP/NADH."),

    ("TCA Cycle",
     "What is the fate of α-Ketoglutarate (5C)?",
     "→ Succinyl-CoA (4C) + CO₂\n"
     "Enzyme: α-Ketoglutarate dehydrogenase complex\n"
     "Cofactors: Same as PDH (B1, B2, B3, B5, lipoic acid)\n"
     "Produces: NADH\n\n"
     "Also: α-KG ↔ Glutamate (transamination)\n"
     "→ Entry point for glutamine/glutamate into TCA\n"
     "→ Key link between amino acid and carbohydrate metabolism"),

    ("TCA Cycle",
     "What is the fate of Succinyl-CoA (4C)?",
     "→ Succinate + GTP\n"
     "Enzyme: Succinyl-CoA synthetase\n"
     "→ Substrate-level phosphorylation (only in TCA)\n\n"
     "Also:\n"
     "→ Heme synthesis (condenses with glycine → ALA)\n"
     "→ Ketone body utilization (succinyl-CoA + acetoacetate → acetyl-CoA)"),

    ("TCA Cycle",
     "What is the fate of Oxaloacetate (OAA, 4C)?",
     "TCA: Condenses with Acetyl-CoA → Citrate (keeps cycle running)\n\n"
     "Also:\n"
     "1. → PEP (via PEPCK) — gluconeogenesis\n"
     "2. → Aspartate (via transamination) — urea cycle nitrogen donor\n"
     "3. → Malate (malate-aspartate shuttle) — NADH transfer\n"
     "4. Anaplerosis: Pyruvate → OAA (pyruvate carboxylase)\n\n"
     "OAA is the most metabolically connected TCA intermediate."),

    ("TCA Cycle",
     "What is the fate of Fumarate (4C)?",
     "TCA: → Malate (fumarase adds H₂O)\n\n"
     "Also appears in:\n"
     "• Urea cycle (product of argininosuccinate lyase step)\n"
     "• Purine synthesis (product of adenylosuccinate lyase)\n\n"
     "Clinical: Fumarate hydratase mutations → hereditary leiomyomatosis\n"
     "and renal cell carcinoma (HLRCC)."),

    # ── OXIDATIVE PHOSPHORYLATION ────────────────────────────────
    ("Oxidative Phosphorylation",
     "What is the fate of NADH produced in metabolism?",
     "→ Donates electrons to Complex I (NADH dehydrogenase) of ETC\n"
     "→ Electrons flow: Complex I → CoQ → Complex III → Cyt c → Complex IV → O₂\n"
     "→ Proton gradient drives ATP synthase (Complex V)\n"
     "→ Yields ~2.5 ATP per NADH\n\n"
     "Note: Cytoplasmic NADH uses malate-aspartate shuttle (2.5 ATP)\n"
     "or glycerol-3-P shuttle (1.5 ATP) to enter ETC."),

    ("Oxidative Phosphorylation",
     "What is the fate of FADH₂ produced in metabolism?",
     "→ Donates electrons to Complex II (succinate dehydrogenase) of ETC\n"
     "→ Bypasses Complex I → enters at CoQ\n"
     "→ Yields ~1.5 ATP per FADH₂\n\n"
     "Sources of FADH₂: TCA (succinate step), beta-oxidation\n"
     "FADH₂ yields less ATP than NADH because it bypasses one proton-pumping complex."),

    ("Oxidative Phosphorylation",
     "What is the fate of the proton gradient (Δψ) across inner mitochondrial membrane?",
     "Generated by: Complexes I, III, IV pumping H⁺ into intermembrane space\n\n"
     "Normally: H⁺ flows back through ATP synthase (Complex V) → ATP synthesis\n\n"
     "If uncoupled (e.g., by DNP, thermogenin/UCP1 in brown fat):\n"
     "→ H⁺ leaks back without making ATP → energy released as heat\n\n"
     "Clinical: Uncoupling is the mechanism of brown fat thermogenesis in neonates."),

    # ── GLUCONEOGENESIS ──────────────────────────────────────────
    ("Gluconeogenesis",
     "What is the fate of Lactate during fasting/exercise?",
     "→ Pyruvate (lactate dehydrogenase; oxidizes NADH → NAD⁺)\n"
     "→ Pyruvate → OAA (pyruvate carboxylase, mitochondria)\n"
     "→ OAA → PEP (PEPCK)\n"
     "→ PEP → Glucose (gluconeogenesis)\n\n"
     "This is the Cori cycle: liver converts muscle lactate → glucose;\n"
     "glucose returns to muscle for further use."),

    ("Gluconeogenesis",
     "What is the fate of Glycerol (from fat breakdown during fasting)?",
     "→ Glycerol-3-phosphate (glycerol kinase, liver)\n"
     "→ DHAP (glycerol-3-P dehydrogenase)\n"
     "→ Enters gluconeogenesis or glycolysis\n\n"
     "Glycerol provides ~5% of gluconeogenic substrate during prolonged fasting.\n"
     "Note: Most cells lack glycerol kinase; only liver/kidney can use glycerol."),

    ("Gluconeogenesis",
     "What is the fate of Alanine from muscle during fasting?",
     "→ Pyruvate + NH₃ (alanine aminotransferase, liver)\n"
     "→ NH₃ → Urea cycle\n"
     "→ Pyruvate → OAA → PEP → Glucose\n\n"
     "This is the Glucose-Alanine Cycle (Cahill cycle):\n"
     "Muscle: glucose → pyruvate + glutamate → alanine\n"
     "Liver: alanine → pyruvate → glucose (returned to muscle)"),

    # ── GLYCOGEN METABOLISM ──────────────────────────────────────
    ("Glycogen Metabolism",
     "What is the fate of UDP-Glucose?",
     "Main fate: → Glycogen chain (glycogen synthase adds it to non-reducing end)\n\n"
     "Also:\n"
     "→ UDP-Galactose (galactose-1-P uridyl transferase) — lactose synthesis\n"
     "→ Glucuronate formation — detoxification in liver\n"
     "→ Synthesis of glycoproteins and proteoglycans\n\n"
     "UDP-Glucose is the activated donor for glycogen synthesis."),

    ("Glycogen Metabolism",
     "What is the fate of Glucose-1-Phosphate released from glycogen?",
     "→ Glucose-6-phosphate (phosphoglucomutase)\n"
     "Then:\n"
     "• Liver/kidney: G6P → Glucose (glucose-6-phosphatase) → blood glucose\n"
     "• Muscle: G6P → enters glycolysis directly (no G6Pase in muscle)\n\n"
     "This explains why muscle glycogen cannot directly raise blood glucose."),

    # ── BETA-OXIDATION ───────────────────────────────────────────
    ("Beta-Oxidation",
     "What is the fate of Fatty Acyl-CoA in beta-oxidation?",
     "Each cycle removes 2 carbons:\n"
     "Fatty Acyl-CoA (n carbons) →\n"
     "  Fatty Acyl-CoA (n-2 carbons) + Acetyl-CoA + NADH + FADH₂\n\n"
     "Acetyl-CoA fates:\n"
     "1. → TCA cycle (energy, fed/exercise)\n"
     "2. → Ketone bodies (fasting, if OAA limiting)\n"
     "3. → Cholesterol/steroid synthesis"),

    ("Beta-Oxidation",
     "What is the fate of Malonyl-CoA in fatty acid metabolism?",
     "Malonyl-CoA is the first committed intermediate of FA synthesis.\n\n"
     "Synthesized by: Acetyl-CoA carboxylase (ACC)\n"
     "Activated by: insulin, citrate\n"
     "Inhibited by: glucagon, fasting, AMPK\n\n"
     "Key regulatory role: Malonyl-CoA INHIBITS carnitine\n"
     "palmitoyltransferase I (CPT-I) → blocks FA import into mitochondria\n"
     "→ prevents simultaneous FA synthesis AND oxidation."),

    ("Beta-Oxidation",
     "What is the role and fate of Carnitine in beta-oxidation?",
     "Carnitine shuttles long-chain fatty acyl groups across inner mitochondrial membrane.\n\n"
     "Steps:\n"
     "1. Fatty acyl-CoA + Carnitine → Acylcarnitine (CPT-I, outer membrane)\n"
     "2. Acylcarnitine enters mitochondria via translocase\n"
     "3. Acylcarnitine → Fatty acyl-CoA + Carnitine (CPT-II, inner membrane)\n\n"
     "CPT-I is the rate-limiting step of beta-oxidation.\n"
     "Carnitine deficiency → fatty acid oxidation defect → hypoglycemia + muscle weakness."),

    # ── FATTY ACID SYNTHESIS ─────────────────────────────────────
    ("Fatty Acid Synthesis",
     "What is the fate of Acetyl-CoA in the cytoplasm (FA synthesis)?",
     "→ Malonyl-CoA (acetyl-CoA carboxylase, rate-limiting)\n"
     "→ Used as 2C donor by fatty acid synthase (FAS)\n"
     "→ Each cycle adds 2 carbons to the growing chain\n\n"
     "Final product after 7 cycles: Palmitate (16:0)\n"
     "Requires: 7 malonyl-CoA + 1 acetyl-CoA + 14 NADPH"),

    ("Fatty Acid Synthesis",
     "What is the fate of NADPH in anabolic pathways?",
     "NADPH is the key reductive cofactor for biosynthesis:\n"
     "1. FA synthesis — H donor for FAS\n"
     "2. Cholesterol synthesis — multiple reduction steps\n"
     "3. Glutathione reductase — antioxidant defense (RBCs)\n"
     "4. Cytochrome P450 reactions — drug/steroid metabolism\n\n"
     "Sources of NADPH:\n"
     "• Pentose phosphate pathway (main source)\n"
     "• Malic enzyme (malate → pyruvate)\n"
     "• Isocitrate dehydrogenase (cytosolic isoform)"),

    # ── UREA CYCLE ───────────────────────────────────────────────
    ("Urea Cycle",
     "What is the fate of NH₃ (Ammonia) in the body?",
     "Ammonia is TOXIC (especially to brain — causes cerebral edema).\n\n"
     "Transport to liver:\n"
     "• Glutamine (main form in blood): Glu + NH₃ → Gln (glutamine synthetase)\n"
     "• Alanine (from muscle): carries NH₃ from muscle to liver\n\n"
     "In liver:\n"
     "→ NH₃ + HCO₃⁻ → Carbamoyl phosphate (CPS I, mitochondria)\n"
     "→ Enters urea cycle → Urea (excreted by kidney)\n\n"
     "Clinical: CPS I deficiency → hyperammonemia"),

    ("Urea Cycle",
     "What is the fate of Citrulline in the urea cycle?",
     "Synthesized in mitochondria (ornithine + carbamoyl phosphate)\n"
     "→ Transported to cytosol (via ornithine-citrulline antiporter)\n"
     "→ Combines with Aspartate → Argininosuccinate (ATP required)\n"
     "→ Argininosuccinate → Arginine + Fumarate\n\n"
     "Fumarate re-enters TCA cycle (links urea cycle to TCA)\n"
     "Arginine → Ornithine + Urea (arginase)\n"
     "Defect in OTC (ornithine transcarbamylase) → citrullinemia/hyperammonemia"),

    ("Urea Cycle",
     "What is the fate of Ornithine in the urea cycle?",
     "Ornithine is the carrier/regenerating molecule of the urea cycle\n"
     "(analogous to OAA in TCA cycle)\n\n"
     "Accepts carbamoyl group → Citrulline (in mitochondria)\n"
     "Regenerated by arginase at end of cycle\n"
     "Transported back into mitochondria via antiporter\n\n"
     "Also: Ornithine → Polyamines (spermine, spermidine)\n"
     "→ important for cell growth and proliferation"),

    # ── PENTOSE PHOSPHATE PATHWAY ────────────────────────────────
    ("Pentose Phosphate Pathway",
     "What is the fate of Glucose-6-Phosphate in the PPP?",
     "Oxidative branch (irreversible):\n"
     "G6P → 6-Phosphogluconolactone → 6-Phosphogluconate\n"
     "→ Ribulose-5-P + CO₂ + 2 NADPH\n"
     "Enzyme: G6PD (glucose-6-phosphate dehydrogenase) — rate-limiting\n\n"
     "Non-oxidative branch (reversible):\n"
     "Ribulose-5-P ↔ Ribose-5-P (for nucleotide synthesis)\n"
     "or ↔ F6P + G3P (feeds back into glycolysis)\n\n"
     "Clinical: G6PD deficiency → hemolytic anemia with oxidant stress"),

    ("Pentose Phosphate Pathway",
     "What is the fate of Ribose-5-Phosphate?",
     "Two main fates:\n"
     "1. → Nucleotide synthesis\n"
     "   R5P + ATP → PRPP (phosphoribosyl pyrophosphate)\n"
     "   PRPP → purines, pyrimidines, NAD⁺, FAD, CoA\n\n"
     "2. Non-oxidative branch → F6P + G3P → back to glycolysis\n"
     "   (when NADPH needed but nucleotides are not)"),

    # ── KETONE BODY METABOLISM ───────────────────────────────────
    ("Ketone Body Metabolism",
     "What is the fate of HMG-CoA in the liver mitochondria?",
     "→ Acetoacetate + Acetyl-CoA (HMG-CoA lyase)\n"
     "This is KETOGENESIS — occurs only in LIVER mitochondria\n\n"
     "Acetoacetate fates:\n"
     "1. → β-Hydroxybutyrate (main blood transport form)\n"
     "2. → Acetone (spontaneous; exhaled)\n\n"
     "Note: HMG-CoA is also used for cholesterol synthesis — but that\n"
     "pathway is in the CYTOSOL. Location determines fate."),

    ("Ketone Body Metabolism",
     "What is the fate of Acetoacetate in peripheral tissues?",
     "Peripheral tissues (brain, muscle, heart) USE ketones:\n"
     "Acetoacetate + Succinyl-CoA → Acetoacetyl-CoA + Succinate\n"
     "Enzyme: Succinyl-CoA transferase (thiophorase)\n"
     "→ Acetoacetyl-CoA → 2 Acetyl-CoA → TCA → ATP\n\n"
     "Liver LACKS thiophorase → cannot use its own ketones\n\n"
     "Brain: Normally uses glucose; after ~2–3 weeks starvation,\n"
     "ketones supply ~60–70% of brain energy."),
]

# ── Build PDF ────────────────────────────────────────────────────
doc = SimpleDocTemplate(
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    leftMargin=1.8*cm, rightMargin=1.8*cm,
    topMargin=1.8*cm, bottomMargin=1.8*cm,
    title="Biochemistry Pathway Intermediates — Flashcard Deck",
    author="Orris Medical"
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styles = getSampleStyleSheet()

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# ── Cover page ───────────────────────────────────────────────────
def cover_flowables():
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        [
            Spacer(1, 1.2*cm),
            Paragraph("BIOCHEMISTRY", STYLE_COVER_TITLE),
            Paragraph("Pathway Intermediates &amp; Their Fates", STYLE_COVER_TITLE),
            Spacer(1, 0.4*cm),
            Paragraph("Flashcard Deck", STYLE_COVER_SUB),
            Spacer(1, 0.2*cm),
            Paragraph("30 Cards · 10 Pathways", STYLE_COVER_SUB),
            Spacer(1, 0.6*cm),
            Paragraph("Glycolysis · TCA Cycle · Oxidative Phosphorylation · Gluconeogenesis", STYLE_COVER_SUB),
            Paragraph("Glycogen Metabolism · Beta-Oxidation · Fatty Acid Synthesis", STYLE_COVER_SUB),
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    # How to use box
    how_data = [[
        Paragraph(
            "<b>How to Use:</b> Cover the ANSWER section and try to recall the fate of each intermediate. "
            "Check your answer by reading the ANSWER / FATE section. "
            "Cards are grouped by pathway and colour-coded for easy navigation.",
            ParagraphStyle("HowTo", parent=styles["Normal"],
                fontSize=10, textColor=C_BLACK, leading=14)
        )
    ]]
    how_table = Table(how_data, colWidths=[PAGE_W])
    how_table.setStyle(TableStyle([
        ("BACKGROUND",   (0,0), (-1,-1), colors.HexColor("#FFF8E1")),
        ("BOX",          (0,0), (-1,-1), 1, C_ACCENT),
        ("ROUNDEDCORNERS", [6]),
        ("LEFTPADDING",  (0,0), (-1,-1), 14),
        ("RIGHTPADDING", (0,0), (-1,-1), 14),
        ("TOPPADDING",   (0,0), (-1,-1), 10),
        ("BOTTOMPADDING",(0,0), (-1,-1), 10),
    ]))
    items.append(how_table)
    items.append(PageBreak())
    return items

# ── Group cards by category ──────────────────────────────────────
from collections import OrderedDict
grouped = OrderedDict()
for card in CARDS:
    cat = card[0]
    grouped.setdefault(cat, []).append(card)

# ── Build story ──────────────────────────────────────────────────
story = cover_flowables()

card_num = 1
for cat, cards_in_cat in grouped.items():
    hdr_bg, card_bg = CAT_COLOURS.get(cat, (C_NAVY, C_GRAY_LT))
    story.append(make_header_table(f"  {cat}", hdr_bg))
    story.append(Spacer(1, 0.25*cm))

    for _, q, a in cards_in_cat:
        fc = make_flashcard(q, a, card_bg, card_num)
        story.append(KeepTogether([fc, Spacer(1, 0.3*cm)]))
        card_num += 1

    story.append(Spacer(1, 0.4*cm))

# ── Build ────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF written: {OUTPUT}")
print(f"Total cards: {card_num - 1}")