#!/usr/bin/env python3
"""
Biochemistry NEET PG / INICET High Yield Previous Year Questions PDF Generator
Uses reportlab for professional PDF output
"""

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

OUTPUT_PATH = "/home/daytona/workspace/biochemistry-neet-pg/Biochemistry_NEET_PG_INICET_HighYield_PYQs.pdf"

# ─── QUESTION DATA ─────────────────────────────────────────────────────────────
questions = [

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 1 – ENZYME KINETICS & REGULATION
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Enzyme Kinetics & Regulation",
  "no": 1,
  "year": "NEET PG 2022",
  "q": "Which of the following best describes the Michaelis constant (Km)?",
  "opts": [
      "A. Substrate concentration at which velocity = Vmax",
      "B. Substrate concentration at which velocity = Vmax/2",
      "C. Maximum velocity of an enzyme-catalyzed reaction",
      "D. Inhibitor concentration that halves Vmax"
  ],
  "ans": "B",
  "exp": (
      "Km (Michaelis constant) is the substrate concentration at which reaction velocity equals Vmax/2. "
      "A low Km indicates high affinity (enzyme is half-saturated at a low [S]); a high Km indicates low affinity. "
      "Km is derived from the Michaelis-Menten equation: v = Vmax[S] / (Km + [S]). "
      "The Lineweaver-Burk (double-reciprocal) plot gives x-intercept = -1/Km and y-intercept = 1/Vmax, "
      "allowing graphical determination of these kinetic constants. "
      "(Harper's Illustrated Biochemistry, 32nd Ed; Lippincott Biochemistry 8th Ed)"
  )
},
{
  "section": "Enzyme Kinetics & Regulation",
  "no": 2,
  "year": "INICET Nov 2022",
  "q": "In competitive inhibition, which of the following is TRUE?",
  "opts": [
      "A. Both Km and Vmax increase",
      "B. Km increases; Vmax remains unchanged",
      "C. Km decreases; Vmax remains unchanged",
      "D. Both Km and Vmax decrease"
  ],
  "ans": "B",
  "exp": (
      "In competitive inhibition the inhibitor competes with substrate for the active site. "
      "Adding more substrate can overcome the inhibitor - hence Vmax is UNCHANGED. "
      "However, apparent Km increases (higher [S] needed to reach Vmax/2). "
      "On a Lineweaver-Burk plot: lines intersect on the y-axis (same Vmax, different x-intercepts). "
      "Classic example: Methotrexate competitively inhibits dihydrofolate reductase (DHFR). "
      "In non-competitive inhibition: Km unchanged, Vmax decreases. "
      "(Lippincott Biochemistry 8th Ed, Chapter 5)"
  )
},
{
  "section": "Enzyme Kinetics & Regulation",
  "no": 3,
  "year": "NEET PG 2021",
  "q": "Which enzyme shows sigmoidal kinetics and is an example of allosteric regulation?",
  "opts": [
      "A. Hexokinase",
      "B. Glucokinase (Hexokinase IV)",
      "C. Lactate dehydrogenase",
      "D. Glycogen phosphorylase b"
  ],
  "ans": "B",
  "exp": (
      "Glucokinase (Hexokinase IV, found in liver and beta cells) shows sigmoidal (S-shaped) kinetics "
      "because it has cooperative substrate binding - fitting the definition of an allosteric enzyme. "
      "Its S0.5 for glucose is ~10 mM (high Km), meaning it is only active after a meal when glucose is high. "
      "Hexokinase (I-III) follows classic Michaelis-Menten hyperbolic kinetics with low Km (~0.1 mM). "
      "Glucokinase is NOT inhibited by its product glucose-6-phosphate - this is key to its role as a 'glucose sensor'. "
      "(Basic Medical Biochemistry, 6e; Harper's 32nd Ed)"
  )
},
{
  "section": "Enzyme Kinetics & Regulation",
  "no": 4,
  "year": "INICET May 2023",
  "q": "Which of the following is a SERINE PROTEASE?",
  "opts": [
      "A. Pepsin",
      "B. Chymotrypsin",
      "C. Carboxypeptidase A",
      "D. Aspartate aminotransferase"
  ],
  "ans": "B",
  "exp": (
      "Serine proteases use a catalytic triad of Serine-Histidine-Aspartate at the active site. "
      "Chymotrypsin, trypsin, elastase, thrombin, and factor Xa are classic serine proteases. "
      "Pepsin is an ASPARTYL protease (active at pH 1-2 in gastric acid). "
      "Carboxypeptidase A is a METALLOPROTEASE (zinc-dependent, exopeptidase). "
      "Zymogen activation: Chymotrypsinogen -> chymotrypsin (by trypsin). "
      "DIPF (diisopropyl fluorophosphate) irreversibly inhibits serine proteases - tested in NEET PG. "
      "(Lippincott Biochemistry 8th Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 2 – CARBOHYDRATE METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Carbohydrate Metabolism",
  "no": 5,
  "year": "NEET PG 2023",
  "q": "The rate-limiting enzyme of glycolysis is:",
  "opts": [
      "A. Hexokinase",
      "B. Phosphofructokinase-1 (PFK-1)",
      "C. Pyruvate kinase",
      "D. Phosphoglucose isomerase"
  ],
  "ans": "B",
  "exp": (
      "Phosphofructokinase-1 (PFK-1) is the KEY regulatory (rate-limiting) enzyme of glycolysis. "
      "It phosphorylates fructose-6-phosphate to fructose-1,6-bisphosphate. "
      "ACTIVATORS of PFK-1: AMP, ADP, fructose-2,6-bisphosphate, Pi. "
      "INHIBITORS of PFK-1: ATP, citrate, H+ (acidosis). "
      "Fructose-2,6-bisphosphate (made by PFK-2) is the most potent allosteric activator - "
      "this is the mechanism by which insulin stimulates glycolysis. "
      "Irreversible steps of glycolysis: Hexokinase, PFK-1, Pyruvate kinase. "
      "(Harper's 32nd Ed; Lippincott 8th Ed)"
  )
},
{
  "section": "Carbohydrate Metabolism",
  "no": 6,
  "year": "INICET Nov 2021",
  "q": "Pyruvate kinase deficiency causes which type of anemia?",
  "opts": [
      "A. Sickle cell anemia",
      "B. Megaloblastic anemia",
      "C. Hemolytic anemia",
      "D. Iron deficiency anemia"
  ],
  "ans": "C",
  "exp": (
      "Pyruvate kinase (PK) deficiency is the most common enzyme deficiency of the Embden-Meyerhof pathway. "
      "PK catalyzes the final step of glycolysis (PEP -> Pyruvate + ATP). "
      "RBCs depend entirely on glycolysis for ATP; PK deficiency -> ATP depletion -> rigid RBCs -> "
      "extravascular hemolysis -> hemolytic anemia (non-spherocytic). "
      "Features: chronic hemolytic anemia, jaundice, splenomegaly, gallstones. "
      "Inheritance: Autosomal recessive (unlike G6PD deficiency which is X-linked). "
      "G6PD deficiency > PK deficiency in prevalence. "
      "(Harrison's 22E; Barash Clinical Anesthesia 9e)"
  )
},
{
  "section": "Carbohydrate Metabolism",
  "no": 7,
  "year": "NEET PG 2022",
  "q": "HbA1c reflects average blood glucose over how many days?",
  "opts": [
      "A. 7-14 days",
      "B. 30-45 days",
      "C. 60-90 days (approximately 120 days RBC lifespan)",
      "D. 6 months"
  ],
  "ans": "C",
  "exp": (
      "HbA1c (glycated hemoglobin) is formed by NON-ENZYMATIC attachment (glycation) of glucose "
      "to the N-terminal valine of the beta chain of hemoglobin. "
      "The fraction glycated is proportional to mean blood glucose over the RBC lifespan (~120 days). "
      "HbA1c reflects ~2-3 months of average glycemia. Normal: <5.7%; Prediabetes: 5.7-6.4%; "
      "Diabetes: ≥6.5%; Treatment target: <7% (ADA). "
      "HbA1c is FALSELY LOW in: hemolytic anemia, sickle cell, recent blood transfusion (shortened RBC lifespan). "
      "HbA1c is FALSELY HIGH in: iron deficiency anemia, vitamin B12 deficiency (increased RBC lifespan). "
      "(Harper's 32nd Ed; Tietz Lab Medicine 7th Ed)"
  )
},
{
  "section": "Carbohydrate Metabolism",
  "no": 8,
  "year": "INICET May 2022",
  "q": "Which is the committed step of gluconeogenesis?",
  "opts": [
      "A. Pyruvate carboxylase",
      "B. Fructose-1,6-bisphosphatase",
      "C. PEPCK (Phosphoenolpyruvate carboxykinase)",
      "D. Glucose-6-phosphatase"
  ],
  "ans": "B",
  "exp": (
      "The UNIQUE (bypass) enzymes of gluconeogenesis (opposing the irreversible glycolysis steps) are: "
      "1. Pyruvate carboxylase (Pyruvate -> OAA; mitochondria; requires Biotin) "
      "2. PEPCK (OAA -> PEP; induced by glucagon/cortisol) "
      "3. Fructose-1,6-bisphosphatase (F1,6BP -> F6P; cytoplasm) - COMMITTED step / rate-limiting "
      "4. Glucose-6-phosphatase (G6P -> Glucose; ER; only in liver, kidney, intestine). "
      "Fructose-1,6-bisphosphatase is inhibited by AMP, fructose-2,6-bisphosphate (insulin effect). "
      "(Lippincott 8th Ed Chapter 10)"
  )
},
{
  "section": "Carbohydrate Metabolism",
  "no": 9,
  "year": "NEET PG 2020",
  "q": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency primarily affects which pathway?",
  "opts": [
      "A. Glycolysis",
      "B. TCA cycle",
      "C. Pentose phosphate pathway (HMP shunt)",
      "D. Glycogen synthesis"
  ],
  "ans": "C",
  "exp": (
      "G6PD is the FIRST and rate-limiting enzyme of the Pentose Phosphate Pathway (HMP shunt / hexose monophosphate shunt). "
      "G6PD generates NADPH, which is essential for: "
      "- Glutathione reductase activity (GSH maintenance to protect RBCs from oxidative damage) "
      "- Fatty acid synthesis, steroid synthesis, phagocyte respiratory burst. "
      "G6PD deficiency: X-linked recessive; most common enzymopathy worldwide. "
      "Triggers: Primaquine, dapsone, sulfonamides, fava beans, infection. "
      "Blood film: Heinz bodies (denatured Hb), bite cells (after spleen removes Heinz bodies). "
      "RBCs are most vulnerable because they lack mitochondria and CANNOT regenerate NADPH otherwise. "
      "(Harrison's 22E; Goldman-Cecil Medicine)"
  )
},
{
  "section": "Carbohydrate Metabolism",
  "no": 10,
  "year": "INICET Nov 2022",
  "q": "Von Gierke disease (Type I glycogen storage disease) is due to deficiency of which enzyme?",
  "opts": [
      "A. Glycogen phosphorylase",
      "B. Glucose-6-phosphatase",
      "C. Acid maltase (alpha-glucosidase)",
      "D. Debranching enzyme"
  ],
  "ans": "B",
  "exp": (
      "Glycogen Storage Diseases (GSDs) - HIGH YIELD TABLE: "
      "Type I (Von Gierke): Glucose-6-phosphatase deficiency; liver, kidney; severe fasting hypoglycemia, "
      "lactic acidosis, hyperuricemia, hyperlipidemia. "
      "Type II (Pompe): Acid maltase (alpha-1,4 glucosidase) deficiency; lysosomal; cardiomegaly. "
      "Type III (Cori/Forbes): Debranching enzyme; limit dextrin accumulates. "
      "Type V (McArdle): Muscle glycogen phosphorylase; exercise intolerance, myoglobinuria. "
      "Type VI (Hers): Liver glycogen phosphorylase. "
      "Von Gierke hallmark: Glucose-6-phosphatase is absent in liver/kidney/intestine - "
      "glucose CANNOT be released from glycogen OR gluconeogenesis -> profound hypoglycemia. "
      "(Lippincott Biochemistry 8th Ed; Harper's 32nd Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 3 – LIPID METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Lipid Metabolism",
  "no": 11,
  "year": "NEET PG 2023",
  "q": "Rate-limiting enzyme of cholesterol synthesis is:",
  "opts": [
      "A. Squalene synthase",
      "B. HMG-CoA reductase",
      "C. Thiolase",
      "D. HMG-CoA synthase"
  ],
  "ans": "B",
  "exp": (
      "HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase) is the RATE-LIMITING enzyme "
      "of cholesterol biosynthesis (mevalonate pathway). "
      "It converts HMG-CoA -> Mevalonate. "
      "STATINS (e.g. atorvastatin, simvastatin) competitively inhibit HMG-CoA reductase - "
      "they are the most widely prescribed lipid-lowering drugs. "
      "Regulation: Insulin & T3 induce HMG-CoA reductase; glucagon & cortisol suppress it. "
      "Cholesterol and oxysterols suppress it (feedback). "
      "PCSK9 inhibitors (evolocumab) work downstream by preventing LDL receptor degradation. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Lipid Metabolism",
  "no": 12,
  "year": "INICET May 2021",
  "q": "Carnitine is required for transport of which molecules into mitochondria?",
  "opts": [
      "A. Short-chain fatty acids",
      "B. Long-chain fatty acyl-CoA",
      "C. Acetyl-CoA",
      "D. Ketone bodies"
  ],
  "ans": "B",
  "exp": (
      "Long-chain fatty acids (>12 carbons) CANNOT cross the inner mitochondrial membrane as CoA esters. "
      "They are converted to acylcarnitine by CARNITINE ACYLTRANSFERASE I (CPT-I) on the outer "
      "mitochondrial membrane, transported by a translocase, then reconverted to acyl-CoA by CPT-II inside. "
      "CPT-I is inhibited by MALONYL-CoA (thus when FA synthesis is active, beta-oxidation is suppressed). "
      "Primary carnitine deficiency -> impaired long-chain FA oxidation -> cardiomyopathy, hypoglycemia. "
      "Short-chain fatty acids (<12C) can diffuse freely across the membrane (no carnitine needed). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Lipid Metabolism",
  "no": 13,
  "year": "NEET PG 2021",
  "q": "Which lipoprotein carries dietary (exogenous) triglycerides from intestine to peripheral tissues?",
  "opts": [
      "A. VLDL",
      "B. LDL",
      "C. Chylomicrons",
      "D. IDL"
  ],
  "ans": "C",
  "exp": (
      "LIPOPROTEIN FUNCTIONS (High-yield): "
      "- Chylomicrons: Synthesized in INTESTINAL EPITHELIUM; carry exogenous (dietary) TGs to peripheral tissues. "
      "  Degraded by lipoprotein lipase (LPL) in capillaries; remnants taken up by liver via ApoE. "
      "- VLDL: Made in LIVER; carry endogenous TGs. Degraded by LPL -> IDL -> LDL. "
      "- LDL: 'Bad' cholesterol; delivers cholesterol to tissues; taken up by LDL receptors (ApoB-100). "
      "- HDL: 'Good' cholesterol; reverse cholesterol transport via ApoA-I; LCAT esterifies cholesterol. "
      "Abetalipoproteinemia: inability to synthesize ApoB-48 (chylomicrons) and ApoB-100 (VLDL/LDL) -> "
      "fat malabsorption, acanthocytosis, ataxia, retinitis pigmentosa. "
      "(Lippincott 8th Ed)"
  )
},
{
  "section": "Lipid Metabolism",
  "no": 14,
  "year": "INICET Nov 2023",
  "q": "Ketone bodies are synthesized in which organ?",
  "opts": [
      "A. Brain",
      "B. Skeletal muscle",
      "C. Liver",
      "D. Kidney"
  ],
  "ans": "C",
  "exp": (
      "Ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) are synthesized ONLY IN HEPATIC MITOCHONDRIA. "
      "Key enzyme: HMG-CoA synthase (mitochondrial) - rate-limiting for ketogenesis. "
      "Ketone bodies are USED but NOT synthesized by: brain, muscle, kidney (they lack mitochondrial HMG-CoA synthase). "
      "Conditions causing ketosis: starvation, uncontrolled T1DM, low-carb diet, alcoholism. "
      "In DKA: beta-hydroxybutyrate > acetoacetate (ratio normally 3:1, in severe DKA up to 7:1). "
      "Note: Acetone is volatile -> fruity (acetone) breath in ketoacidosis. "
      "Ketone bodies are WATER-SOLUBLE alternative fuels - do not need albumin for transport. "
      "(Harper's 32nd Ed; Lippincott 8th Ed)"
  )
},
{
  "section": "Lipid Metabolism",
  "no": 15,
  "year": "NEET PG 2022",
  "q": "Essential fatty acids that CANNOT be synthesized by humans include:",
  "opts": [
      "A. Palmitic acid and stearic acid",
      "B. Linoleic acid (omega-6) and alpha-linolenic acid (omega-3)",
      "C. Oleic acid and arachidonic acid",
      "D. Docosahexaenoic acid (DHA) only"
  ],
  "ans": "B",
  "exp": (
      "Humans lack delta-12 and delta-15 desaturases, therefore CANNOT synthesize: "
      "1. Linoleic acid (18:2, omega-6) - precursor to arachidonic acid and eicosanoids "
      "2. Alpha-linolenic acid (18:3, omega-3) - precursor to EPA and DHA "
      "These are TRUE essential fatty acids (must be obtained from diet). "
      "Deficiency: Scaly dermatitis, impaired wound healing, increased susceptibility to infections. "
      "Arachidonic acid can be synthesized FROM linoleic acid, so it is 'conditionally essential'. "
      "DHA (22:6 omega-3) is important for brain and retinal development in infants. "
      "(Harper's 32nd Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 4 – PROTEIN & AMINO ACID METABOLISM
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Protein & Amino Acid Metabolism",
  "no": 16,
  "year": "NEET PG 2023",
  "q": "Phenylketonuria (PKU) is caused by deficiency of which enzyme?",
  "opts": [
      "A. Tyrosine hydroxylase",
      "B. Phenylalanine hydroxylase",
      "C. Homogentisate oxidase",
      "D. Fumarylacetoacetase"
  ],
  "ans": "B",
  "exp": (
      "Classic PKU (Type I): Deficiency of phenylalanine hydroxylase (PAH) - AR inheritance; "
      "frequency 1/10,000 births. PAH converts Phe -> Tyr (requires BH4 - tetrahydrobiopterin as cofactor). "
      "Accumulation: phenylalanine and phenylpyruvate (phenylketones). "
      "Features: Intellectual disability (if untreated), fair skin/hair (reduced melanin because Tyr is deficient), "
      "musty/mousy urine odor, seizures, eczema. "
      "Treatment: Phenylalanine-restricted diet (avoid aspartame which contains phenylalanine). "
      "Maternal PKU: Uncontrolled PKU during pregnancy -> microcephaly, congenital heart defects in infant. "
      "Types II & III: Dihydrobiopterin reductase deficiency (BH4 recycling defect). "
      "(Harper's 32nd Ed; Ganong's Physiology)"
  )
},
{
  "section": "Protein & Amino Acid Metabolism",
  "no": 17,
  "year": "INICET May 2022",
  "q": "Alkaptonuria is caused by deficiency of which enzyme?",
  "opts": [
      "A. Fumarylacetoacetase",
      "B. Maleylacetoacetate isomerase",
      "C. Homogentisate oxidase (homogentisic acid oxidase)",
      "D. 4-Hydroxyphenylpyruvate dioxygenase"
  ],
  "ans": "C",
  "exp": (
      "Alkaptonuria = Deficiency of HOMOGENTISATE OXIDASE (homogentisic acid oxidase). "
      "Homogentisic acid accumulates -> excreted in urine (urine turns black on standing). "
      "Triad: (1) Dark urine on exposure to air, (2) Ochronosis (bluish-black pigment in cartilage, sclera), "
      "(3) Arthritis (ochronotic arthropathy) in 4th-5th decade. "
      "AR inheritance. Benign until adult life. Confirmed by increased homogentisic acid in urine. "
      "Tyrosinemia Type I: Fumarylacetoacetase deficiency -> hepatorenal syndrome, liver failure. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Protein & Amino Acid Metabolism",
  "no": 18,
  "year": "NEET PG 2021",
  "q": "Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. Its inheritance pattern is:",
  "opts": [
      "A. Autosomal dominant",
      "B. Autosomal recessive",
      "C. X-linked recessive",
      "D. Mitochondrial inheritance"
  ],
  "ans": "C",
  "exp": (
      "OTC (Ornithine transcarbamylase) deficiency is: "
      "- Most COMMON urea cycle disorder "
      "- X-LINKED (unlike all other urea cycle defects which are autosomal recessive) "
      "- OTC catalyzes: Carbamoyl phosphate + Ornithine -> Citrulline (step 2 of urea cycle, in mitochondria) "
      "Features: Hyperammonemia, elevated glutamine, DECREASED citrulline, INCREASED orotic acid in urine "
      "(distinguishes from CPS-I deficiency where orotic acid is normal). "
      "Treatment: Low-protein diet, sodium benzoate/phenylbutyrate (alternative nitrogen excretion routes), "
      "liver transplantation (definitive). "
      "(Harrison's 22E; Tintinalli Emergency Medicine)"
  )
},
{
  "section": "Protein & Amino Acid Metabolism",
  "no": 19,
  "year": "INICET Nov 2022",
  "q": "Which amino acid is the precursor for both serotonin and melatonin?",
  "opts": [
      "A. Tyrosine",
      "B. Tryptophan",
      "C. Phenylalanine",
      "D. Histidine"
  ],
  "ans": "B",
  "exp": (
      "TRYPTOPHAN is the precursor for: "
      "- Serotonin (5-HT): Trp -> 5-HTP (by tryptophan hydroxylase, rate-limiting; requires BH4) -> "
      "  5-HT (by AAAD - aromatic amino acid decarboxylase; requires PLP/B6). "
      "  Serotonin -> Melatonin (by HIOMT in pineal gland). "
      "- Niacin (Vitamin B3): 60 mg Trp = 1 mg niacin. Deficiency in carcinoid syndrome, Hartnup disease. "
      "- Kynurenine pathway (90% of Trp): -> NAD+. "
      "TYROSINE is the precursor for: Dopamine, Norepinephrine, Epinephrine, Melanin, T3/T4, DOPA. "
      "HISTIDINE -> Histamine (by histidine decarboxylase; requires PLP). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Protein & Amino Acid Metabolism",
  "no": 20,
  "year": "NEET PG 2022",
  "q": "Maple Syrup Urine Disease (MSUD) involves deficiency of which enzyme?",
  "opts": [
      "A. Leucine aminotransferase",
      "B. Branched-chain alpha-keto acid dehydrogenase (BCKD)",
      "C. Isovaleryl-CoA dehydrogenase",
      "D. Alpha-ketoglutarate dehydrogenase"
  ],
  "ans": "B",
  "exp": (
      "MSUD = Deficiency of BCKD (Branched-chain alpha-keto acid dehydrogenase complex). "
      "Affected amino acids: Leucine, Isoleucine, Valine (BCAAs - branched chain). "
      "Accumulation of branched-chain keto acids -> maple syrup/burnt sugar odor in urine/earwax. "
      "Features: Encephalopathy, poor feeding, seizures, opisthotonos in neonates; if untreated -> death. "
      "Treatment: BCAA-restricted diet; thiamine responsive in some variants (cofactor for BCKD is thiamine-TPP). "
      "BCKD complex is analogous to Pyruvate dehydrogenase complex (both require: TPP, Lipoic acid, FAD, NAD+, CoA). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 5 – VITAMINS & COFACTORS
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Vitamins & Cofactors",
  "no": 21,
  "year": "NEET PG 2023",
  "q": "Vitamin C (ascorbic acid) is essential for collagen synthesis because it is required for:",
  "opts": [
      "A. Glycosylation of collagen",
      "B. Hydroxylation of proline and lysine residues",
      "C. Cross-linking of collagen fibers",
      "D. Translation of collagen mRNA"
  ],
  "ans": "B",
  "exp": (
      "Vitamin C (Ascorbic acid) activates PROLYL and LYSYL HYDROXYLASES which catalyze "
      "hydroxylation of proline -> hydroxyproline and lysine -> hydroxylysine. "
      "These hydroxy residues are essential for: "
      "- Hydrogen bond formation within the triple helix -> stability "
      "- Glycosylation attachment sites "
      "- Cross-link formation (via lysyl oxidase, which needs Cu2+). "
      "In SCURVY (Vit C deficiency): defective proline hydroxylation -> unstable triple helix -> "
      "perifollicular hemorrhages, gum bleeding, poor wound healing, corkscrew hairs. "
      "Vit C also has antioxidant properties and regenerates Vit E. "
      "(Robbins Basic Pathology; Sabiston Surgery 8th Ed)"
  )
},
{
  "section": "Vitamins & Cofactors",
  "no": 22,
  "year": "INICET Nov 2021",
  "q": "Thiamine (Vitamin B1) deficiency causes which metabolic block?",
  "opts": [
      "A. Inhibition of oxidative phosphorylation",
      "B. Block at pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase",
      "C. Inhibition of glycogen synthesis",
      "D. Block at HMG-CoA reductase"
  ],
  "ans": "B",
  "exp": (
      "Thiamine (B1) as TPP (Thiamine Pyrophosphate) is a cofactor for: "
      "1. Pyruvate Dehydrogenase Complex (PDC): Pyruvate -> Acetyl-CoA "
      "2. Alpha-ketoglutarate Dehydrogenase: Alpha-KG -> Succinyl-CoA (TCA cycle) "
      "3. Transketolase (HMP shunt) "
      "4. Branched-chain keto acid dehydrogenase (BCKD) "
      "Deficiency -> Pyruvate accumulates -> lactic acidosis. "
      "Clinical syndromes: "
      "- Dry Beriberi: Peripheral neuropathy "
      "- Wet Beriberi: High-output cardiac failure + edema "
      "- Wernicke's encephalopathy (alcoholics): Confusion, ataxia, ophthalmoplegia "
      "- Korsakoff syndrome: Anterograde amnesia, confabulation "
      "- Leigh disease (subacute necrotizing encephalopathy): Pediatric. "
      "(Lippincott 8th Ed; Robbins Pathology)"
  )
},
{
  "section": "Vitamins & Cofactors",
  "no": 23,
  "year": "NEET PG 2021",
  "q": "Which vitamin deficiency causes pellagra (4 Ds: Dermatitis, Diarrhea, Dementia, Death)?",
  "opts": [
      "A. Vitamin B6 (Pyridoxine)",
      "B. Vitamin B12 (Cobalamin)",
      "C. Vitamin B3 (Niacin)",
      "D. Vitamin B2 (Riboflavin)"
  ],
  "ans": "C",
  "exp": (
      "PELLAGRA = Niacin (Vitamin B3) deficiency (or tryptophan deficiency, since Trp -> Niacin). "
      "4 Ds: Dermatitis (photosensitive, Casal's necklace), Diarrhea, Dementia, Death. "
      "Niacin forms NAD+ and NADP+ - essential coenzymes in >400 redox reactions. "
      "Causes of pellagra: "
      "1. Poor diet (maize-based diet - maize lacks tryptophan and niacin in bioavailable form) "
      "2. Carcinoid syndrome (tryptophan diverted to serotonin) "
      "3. Hartnup disease (tryptophan malabsorption - AR) "
      "4. Isoniazid treatment (inhibits B6 needed for Trp -> Niacin conversion) "
      "Treatment: Nicotinamide (niacinamide) - no flushing vs niacin. "
      "High-dose niacin: lowers TGs, raises HDL (causes flushing, prevented by aspirin). "
      "(Robbins Pathology; Lippincott 8th Ed)"
  )
},
{
  "section": "Vitamins & Cofactors",
  "no": 24,
  "year": "INICET May 2023",
  "q": "Biotin is the cofactor for which class of enzymes?",
  "opts": [
      "A. Decarboxylases",
      "B. Carboxylases (CO2-fixing enzymes)",
      "C. Transaminases",
      "D. Dehydrogenases"
  ],
  "ans": "B",
  "exp": (
      "Biotin (Vitamin B7/H) is the cofactor for CARBOXYLASES (CO2-fixing enzymes): "
      "1. Pyruvate Carboxylase: Pyruvate -> OAA (gluconeogenesis; mitochondria) "
      "2. Acetyl-CoA Carboxylase: Acetyl-CoA -> Malonyl-CoA (RATE-LIMITING step of FA synthesis) "
      "3. Propionyl-CoA Carboxylase: Propionyl-CoA -> Methylmalonyl-CoA "
      "4. Beta-methylcrotonyl-CoA carboxylase (leucine catabolism) "
      "Biotin deficiency: Caused by excess raw egg white consumption (avidin binds biotin) or "
      "prolonged TPN. Features: Dermatitis, alopecia, neurological changes, organic aciduria. "
      "PLP (B6) is the cofactor for TRANSAMINASES (aminotransferases). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Vitamins & Cofactors",
  "no": 25,
  "year": "NEET PG 2022",
  "q": "Vitamin K is required for the synthesis of which coagulation factors?",
  "opts": [
      "A. Factors I, II, V, VIII",
      "B. Factors II, VII, IX, X and Protein C, S",
      "C. Factors VIII, IX, X, XI",
      "D. Factors III, IV, VII, X"
  ],
  "ans": "B",
  "exp": (
      "Vitamin K is a fat-soluble vitamin required as a cofactor for gamma-carboxylation of glutamate "
      "residues in clotting factors. Vitamin K-DEPENDENT factors (mnemonic 1972): "
      "Factors II (prothrombin), VII, IX, X + Protein C, S, Z. "
      "Mechanism: Vit K (hydroquinone form) enables carboxylation of Glu -> Gla (gamma-carboxyglutamate) "
      "which allows Ca2+ binding and membrane attachment of clotting factors. "
      "Vit K is recycled by VKOR (Vitamin K Epoxide Reductase) - target of WARFARIN. "
      "Deficiency causes: Hemorrhagic disease of newborn (given IM Vit K1 at birth prophylactically), "
      "bleeding on warfarin, fat malabsorption syndromes. "
      "Vit K2 (menaquinone) also involved in bone mineralization (osteocalcin). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 6 – NUCLEOTIDE METABOLISM & MOLECULAR BIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Nucleotide Metabolism & Molecular Biology",
  "no": 26,
  "year": "NEET PG 2023",
  "q": "Lesch-Nyhan syndrome is caused by deficiency of which enzyme?",
  "opts": [
      "A. Adenosine deaminase (ADA)",
      "B. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)",
      "C. Xanthine oxidase",
      "D. Purine nucleoside phosphorylase"
  ],
  "ans": "B",
  "exp": (
      "Lesch-Nyhan syndrome = HGPRT deficiency (Hypoxanthine-Guanine Phosphoribosyltransferase). "
      "Inheritance: X-LINKED RECESSIVE (affects males). "
      "HGPRT is required for PURINE SALVAGE PATHWAY: "
      "Hypoxanthine + PRPP -> IMP and Guanine + PRPP -> GMP. "
      "Without salvage: purines -> uric acid in excess -> HYPERURICEMIA. "
      "Clinical: Hyperuricemia (gout-like arthritis), Uric acid nephropathy, Uric acid stones, "
      "Intellectual disability, Choreoathetosis, SELF-MUTILATION (pathognomonic - biting fingers/lips). "
      "Treatment: Allopurinol (xanthine oxidase inhibitor) for hyperuricemia; no cure for neurological features. "
      "ADA deficiency -> SCID (severe combined immunodeficiency). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Nucleotide Metabolism & Molecular Biology",
  "no": 27,
  "year": "INICET Nov 2022",
  "q": "Which drug inhibits xanthine oxidase and is used to treat gout?",
  "opts": [
      "A. Probenecid",
      "B. Colchicine",
      "C. Allopurinol",
      "D. Febuxostat"
  ],
  "ans": "C",
  "exp": (
      "ALLOPURINOL inhibits XANTHINE OXIDASE (XO), reducing conversion of hypoxanthine and xanthine to uric acid. "
      "Allopurinol itself is a substrate analog (structural analog of hypoxanthine) - suicide inhibitor. "
      "Its active metabolite oxypurinol also inhibits XO. "
      "Uses: Chronic gout prevention, Lesch-Nyhan syndrome, tumor lysis syndrome prevention. "
      "Note: Febuxostat is a non-purine XO inhibitor (selective). "
      "Probenecid: uricosuric (blocks renal tubular reabsorption of urate). "
      "Colchicine: anti-inflammatory for acute gout (inhibits tubulin polymerization -> blocks neutrophil migration). "
      "Rasburicase: recombinant uricase; converts uric acid -> allantoin (more soluble); for tumor lysis. "
      "(Lippincott 8th Ed)"
  )
},
{
  "section": "Nucleotide Metabolism & Molecular Biology",
  "no": 28,
  "year": "NEET PG 2022",
  "q": "The 5' to 3' direction of DNA replication on the lagging strand is accomplished via:",
  "opts": [
      "A. Continuous synthesis",
      "B. Okazaki fragments",
      "C. RNA primer only",
      "D. Helicase activity"
  ],
  "ans": "B",
  "exp": (
      "DNA polymerase can only synthesize DNA in the 5'->3' direction and requires a primer. "
      "LEADING STRAND: synthesized continuously toward the replication fork (5'->3'). "
      "LAGGING STRAND: synthesized in fragments AWAY from the replication fork as short OKAZAKI FRAGMENTS. "
      "Each Okazaki fragment begins with an RNA primer (made by Primase), then DNA is synthesized. "
      "In prokaryotes, DNA Pol I removes RNA primers and fills gaps; DNA ligase seals the nicks. "
      "In eukaryotes, RNase H + FEN1 remove RNA primers; DNA Pol delta fills gaps; DNA ligase I seals. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Nucleotide Metabolism & Molecular Biology",
  "no": 29,
  "year": "INICET May 2022",
  "q": "Which type of RNA carries amino acids to the ribosome during translation?",
  "opts": [
      "A. mRNA",
      "B. rRNA",
      "C. tRNA",
      "D. snRNA"
  ],
  "ans": "C",
  "exp": (
      "tRNA (transfer RNA) = ADAPTOR molecule that: "
      "1. Carries specific amino acids at its 3' CCA-OH terminus "
      "2. Has an ANTICODON loop that base-pairs with the complementary codon on mRNA "
      "Aminoacyl-tRNA synthetases charge tRNAs (one enzyme per amino acid; uses ATP). "
      "rRNA forms the structural and catalytic core of ribosomes (28S rRNA is the ribozyme - peptidyl transferase). "
      "mRNA carries genetic information from DNA to ribosomes. "
      "RIBOSOME SITES: A site (incoming aminoacyl-tRNA), P site (peptidyl-tRNA), E site (exit). "
      "Elongation factors (EF-1alpha in eukaryotes / EF-Tu in prokaryotes) bring aminoacyl-tRNA to A site. "
      "(Lippincott 8th Ed)"
  )
},
{
  "section": "Nucleotide Metabolism & Molecular Biology",
  "no": 30,
  "year": "NEET PG 2023",
  "q": "Reverse transcriptase is used by retroviruses. It synthesizes:",
  "opts": [
      "A. RNA from RNA template",
      "B. DNA from RNA template",
      "C. Protein from DNA template",
      "D. DNA from DNA template"
  ],
  "ans": "B",
  "exp": (
      "Reverse transcriptase (RNA-dependent DNA polymerase) synthesizes DNA using an RNA template. "
      "This is the reverse of the central dogma (DNA -> RNA). "
      "Steps in retrovirus (HIV) replication: "
      "ssRNA genome -> (reverse transcriptase) -> ssDNA -> dsDNA -> (integrase) -> provirus integrated into host. "
      "NRTI/NtRTI drugs (e.g., zidovudine/AZT, tenofovir) inhibit reverse transcriptase by acting as "
      "chain terminators (lack 3'-OH). "
      "Telomerase is a CELLULAR reverse transcriptase that extends telomeres using its own RNA template. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 7 – TCA CYCLE & OXIDATIVE PHOSPHORYLATION
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "TCA Cycle & Oxidative Phosphorylation",
  "no": 31,
  "year": "NEET PG 2022",
  "q": "Which complex of the electron transport chain is inhibited by cyanide?",
  "opts": [
      "A. Complex I (NADH dehydrogenase)",
      "B. Complex II (Succinate dehydrogenase)",
      "C. Complex III (Cytochrome bc1)",
      "D. Complex IV (Cytochrome c oxidase)"
  ],
  "ans": "D",
  "exp": (
      "ETC INHIBITORS (very high yield for NEET PG): "
      "- Complex I: Rotenone, Amytal, Metformin (partial) "
      "- Complex II: None clinically significant (Malonate is experimental) "
      "- Complex III: Antimycin A "
      "- Complex IV (Cytochrome c oxidase): CYANIDE (CN-), Carbon monoxide (CO), Azide, H2S "
      "- ATP synthase (Complex V): Oligomycin "
      "- Uncouplers (allow proton leak without ATP synthesis): 2,4-Dinitrophenol (DNP), Thermogenin (UCP-1), Aspirin (high dose) "
      "Cyanide binds the Fe3+ (ferric) iron of cytochrome a3 (in Complex IV) - prevents O2 binding. "
      "Treatment of cyanide poisoning: Nitrites (form methemoglobin which competes for CN-) + Thiosulfate "
      "(converts CN- to thiocyanate by rhodanese). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "TCA Cycle & Oxidative Phosphorylation",
  "no": 32,
  "year": "INICET Nov 2021",
  "q": "Succinate dehydrogenase is unique in the TCA cycle because it is:",
  "opts": [
      "A. Located in the mitochondrial matrix",
      "B. Part of Complex II of the electron transport chain",
      "C. Only enzyme using NADH",
      "D. Rate-limiting enzyme of TCA cycle"
  ],
  "ans": "B",
  "exp": (
      "Succinate dehydrogenase (Complex II) is unique in the TCA cycle: "
      "1. It is embedded in the INNER MITOCHONDRIAL MEMBRANE (all other TCA enzymes are in the matrix). "
      "2. It is PART OF THE ETC (Complex II) - directly reduces FAD to FADH2. "
      "3. It does NOT produce NADH - directly feeds FADH2 electrons to CoQ (ubiquinone). "
      "Reaction: Succinate -> Fumarate + FADH2. "
      "Competitive inhibitor: Malonate (structural analog of succinate - used in research). "
      "SDHA mutations: Associated with paraganglioma/pheochromocytoma (Carney triad). "
      "Aconitase (TCA cycle) and Isocitrate dehydrogenase (IDH) are commonly tested - IDH mutations in glioma (IDH1 R132H). "
      "(Lippincott 8th Ed)"
  )
},
{
  "section": "TCA Cycle & Oxidative Phosphorylation",
  "no": 33,
  "year": "NEET PG 2021",
  "q": "P/O ratio (ATP produced per oxygen atom consumed) for NADH via oxidative phosphorylation is approximately:",
  "opts": [
      "A. 1",
      "B. 1.5",
      "C. 2",
      "D. 2.5"
  ],
  "ans": "D",
  "exp": (
      "Updated P/O ratios (chemiosmotic theory, revised): "
      "- NADH: P/O ratio = 2.5 (older texts say 3) "
      "- FADH2: P/O ratio = 1.5 (older texts say 2) "
      "The ATP produced per glucose (aerobic): ~30-32 ATP (older texts cited 36-38 ATP). "
      "Source of ATP in glucose oxidation: "
      "- Glycolysis: 2 ATP (substrate level) + 2 NADH (cytoplasmic, enter via malate-aspartate shuttle = 5 ATP or "
      "  glycerol-3-phosphate shuttle = 3 ATP) "
      "- Pyruvate dehydrogenase: 2 NADH = 5 ATP "
      "- TCA cycle: 3 NADH + 1 FADH2 + 1 GTP per turn (x2 turns) = 20 ATP "
      "Total ~30-32 ATP per glucose. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 8 – HEME SYNTHESIS & PORPHYRIAS
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Heme Synthesis & Porphyrias",
  "no": 34,
  "year": "NEET PG 2023",
  "q": "The rate-limiting enzyme of heme synthesis is:",
  "opts": [
      "A. Uroporphyrinogen decarboxylase",
      "B. ALA synthase (delta-aminolevulinic acid synthase)",
      "C. Porphobilinogen (PBG) deaminase",
      "D. Ferrochelatase"
  ],
  "ans": "B",
  "exp": (
      "ALA SYNTHASE (ALAS) is the RATE-LIMITING enzyme of heme synthesis. "
      "Reaction: Succinyl-CoA + Glycine -> ALA (delta-aminolevulinic acid). "
      "Location: MITOCHONDRIA; cofactor: PLP (Pyridoxal phosphate / B6). "
      "Regulation: Inhibited by HEME (end-product feedback inhibition). "
      "Two isoforms: ALAS1 (ubiquitous, inducible by drugs/starvation) and ALAS2 (erythroid-specific, X-linked sideroblastic anemia). "
      "PORPHYRIAS (defects in heme synthesis): "
      "- AIP (Acute Intermittent Porphyria): PBG deaminase deficiency; AD; neurovisceral attacks. "
      "- PCT (Porphyria Cutanea Tarda): Uroporphyrinogen decarboxylase; most common; skin blisters. "
      "- Lead poisoning: inhibits ALA dehydratase (ALA accumulates) and ferrochelatase. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Heme Synthesis & Porphyrias",
  "no": 35,
  "year": "INICET May 2022",
  "q": "In lead poisoning, which enzyme activities in heme synthesis are inhibited?",
  "opts": [
      "A. ALA synthase and PBG deaminase",
      "B. ALA dehydratase and ferrochelatase",
      "C. Uroporphyrinogen decarboxylase and coproporphyrinogen oxidase",
      "D. Protoporphyrinogen oxidase and ferrochelatase"
  ],
  "ans": "B",
  "exp": (
      "LEAD POISONING - heme synthesis enzymes inhibited: "
      "1. ALA DEHYDRATASE (ALAD): ALA -> PBG step blocked -> ALA accumulates in urine. "
      "2. FERROCHELATASE: Fe2+ incorporation into protoporphyrin IX blocked -> ZPP (zinc protoporphyrin) forms instead. "
      "Lab findings: Elevated ALA in urine, elevated erythrocyte ZPP, basophilic stippling of RBCs "
      "(aggregated ribosomes due to inhibition of 5'-nucleotidase), hypochromic microcytic anemia. "
      "Other effects: Wrist/foot drop (motor neuropathy), encephalopathy (children), Burton lines (lead lines on gums). "
      "Treatment: Chelation with EDTA, DMSA (succimer), BAL (dimercaprol); remove from exposure. "
      "(Lippincott 8th Ed; Harrison's 22E)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 9 – CONNECTIVE TISSUE & STRUCTURAL PROTEINS
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Connective Tissue & Structural Proteins",
  "no": 36,
  "year": "NEET PG 2022",
  "q": "Type I collagen is the predominant collagen in which of the following tissues?",
  "opts": [
      "A. Cartilage and vitreous humor",
      "B. Basement membranes",
      "C. Skin, bone, tendon, and cornea",
      "D. Blood vessels (only)"
  ],
  "ans": "C",
  "exp": (
      "COLLAGEN TYPE MNEMONICS (High yield): "
      "Type I ('one bone'): Skin, Bone, Tendon, Cornea, Dentin - most abundant (90% of body collagen) "
      "Type II ('two cartilage'): Cartilage, Vitreous humor, Nucleus pulposus "
      "Type III ('three reticulin'): Reticulin - skin, blood vessels, uterus; Ehlers-Danlos (EDS type IV) "
      "Type IV: Basement membranes (filtration); Alport syndrome; target of anti-GBM antibody in Goodpasture syndrome "
      "Type VII: Anchoring fibrils of skin; Epidermolysis bullosa dystrophica "
      "Osteogenesis Imperfecta: Defect in Type I collagen (COL1A1/COL1A2 mutations). "
      "Collagen synthesis steps: Gene transcription -> prepro-collagen -> cleavage of signal -> procollagen -> "
      "triple helix (in ER) -> secretion -> cleavage of propeptides -> tropocollagen -> cross-linking. "
      "(Robbins Pathology; Sabiston Surgery)"
  )
},
{
  "section": "Connective Tissue & Structural Proteins",
  "no": 37,
  "year": "INICET Nov 2022",
  "q": "Marfan syndrome involves a defect in which protein?",
  "opts": [
      "A. Collagen type I",
      "B. Fibrillin-1",
      "C. Elastin",
      "D. Laminin"
  ],
  "ans": "B",
  "exp": (
      "Marfan Syndrome: Autosomal DOMINANT mutation in FBN1 gene -> defective FIBRILLIN-1. "
      "Fibrillin-1 is a component of microfibrils in extracellular matrix. It normally sequesters TGF-beta. "
      "Defective fibrillin -> excess free TGF-beta -> tissue weakening. "
      "Clinical features: Tall stature, arachnodactyly, hypermobile joints, lens dislocation (ectopia lentis - "
      "upward and outward), aortic root dilatation/dissection, mitral valve prolapse. "
      "Homocystinuria (cystathionine synthase deficiency) also causes lens dislocation but DOWNWARD "
      "and causes intellectual disability, thrombosis - distinguish from Marfan! "
      "Ehlers-Danlos Syndrome: Defect in collagen (various types); skin hyperextensibility, joint hypermobility. "
      "(Robbins Basic Pathology; Harrison's 22E)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 10 – HORMONES, SIGNAL TRANSDUCTION & CLINICAL BIOCHEMISTRY
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Hormones & Signal Transduction",
  "no": 38,
  "year": "NEET PG 2023",
  "q": "Which second messenger is produced by phospholipase C activation?",
  "opts": [
      "A. cAMP only",
      "B. IP3 and DAG",
      "C. cGMP",
      "D. Arachidonic acid only"
  ],
  "ans": "B",
  "exp": (
      "Phospholipase C (PLC) cleaves PIP2 (phosphatidylinositol 4,5-bisphosphate) into: "
      "1. IP3 (Inositol-1,4,5-trisphosphate) -> releases Ca2+ from ER (via IP3 receptors). "
      "2. DAG (Diacylglycerol) -> activates Protein Kinase C (PKC). "
      "This cascade is initiated by Gq-coupled receptors (QISS and QIQQK mnemonic): "
      "Gq: M1, M3 (muscarinic), H1, alpha-1 adrenergic, V1 (vasopressin), oxytocin, GnRH, TRH, angiotensin II. "
      "cAMP pathway: Gs-coupled (increase) or Gi-coupled (decrease). "
      "cGMP pathway: Nitric oxide -> soluble guanylyl cyclase -> cGMP -> PKG. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Hormones & Signal Transduction",
  "no": 39,
  "year": "INICET May 2023",
  "q": "Insulin receptor is classified as which type of receptor?",
  "opts": [
      "A. G-protein coupled receptor (GPCR)",
      "B. Nuclear receptor",
      "C. Receptor tyrosine kinase (RTK)",
      "D. Ligand-gated ion channel"
  ],
  "ans": "C",
  "exp": (
      "Insulin receptor = RECEPTOR TYROSINE KINASE (RTK). "
      "Structure: Heterotetrameric (alpha2-beta2); alpha subunits are extracellular (insulin-binding); "
      "beta subunits are transmembrane with intrinsic tyrosine kinase activity. "
      "Binding insulin -> autophosphorylation of beta subunits -> phosphorylates IRS-1/IRS-2 -> "
      "activates PI3K -> Akt -> GLUT-4 translocation to membrane (in muscle and adipose). "
      "Other RTKs: EGF receptor, PDGF receptor, FGF receptor, IGF-1 receptor. "
      "NUCLEAR RECEPTORS (intracellular): Steroids (GC, MC, sex hormones), Thyroid hormones, Vitamin D, Retinoic acid. "
      "(Lippincott 8th Ed)"
  )
},
{
  "section": "Hormones & Signal Transduction",
  "no": 40,
  "year": "NEET PG 2021",
  "q": "Which enzyme converts angiotensin I to angiotensin II?",
  "opts": [
      "A. Renin",
      "B. Angiotensinogen synthase",
      "C. Angiotensin-converting enzyme (ACE)",
      "D. Neprilysin"
  ],
  "ans": "C",
  "exp": (
      "RAAS Pathway: "
      "Angiotensinogen (liver) -> [Renin from JGA of kidney] -> Angiotensin I (inactive, 10 aa) "
      "-> [ACE - from pulmonary endothelium] -> Angiotensin II (8 aa, active). "
      "Angiotensin II effects: Vasoconstriction (AT1R), aldosterone secretion (adrenal cortex), "
      "ADH release, sympathetic activation, Na+ retention. "
      "ACE INHIBITORS (e.g., lisinopril): Also prevent bradykinin breakdown -> bradykinin accumulates "
      "-> cough (side effect); contraindicated in pregnancy (teratogenic, causes fetal renal failure). "
      "ARBs (e.g., losartan): Block AT1 receptor; no bradykinin effect; less cough. "
      "ACE also degrades: Bradykinin, substance P. "
      "(Guyton & Hall Physiology; Lippincott 8th Ed)"
  )
},

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 11 – ADDITIONAL HIGH-YIELD MCQs
# ══════════════════════════════════════════════════════════════════════════════
{
  "section": "Additional High-Yield MCQs",
  "no": 41,
  "year": "NEET PG 2022",
  "q": "Which vitamin requires intrinsic factor (IF) for absorption?",
  "opts": [
      "A. Folic acid",
      "B. Vitamin B12 (Cobalamin)",
      "C. Vitamin B6",
      "D. Vitamin B1"
  ],
  "ans": "B",
  "exp": (
      "Vitamin B12 (Cobalamin) absorption requires intrinsic factor (IF): "
      "- IF is a glycoprotein secreted by PARIETAL CELLS of gastric fundus. "
      "- B12-IF complex binds cubilin receptor in terminal ILEUM for absorption. "
      "- Deficiency causes: Megaloblastic anemia, subacute combined degeneration of spinal cord "
      "  (dorsal columns + lateral corticospinal tract), glossitis. "
      "Pernicious anemia: Autoimmune destruction of parietal cells (anti-parietal cell + anti-IF antibodies). "
      "Schilling test: Used to differentiate causes of B12 deficiency. "
      "Note: Folic acid absorption is in jejunum and does NOT require IF. "
      "B12 deficiency vs. Folate deficiency: Both cause megaloblastic anemia; "
      "B12 deficiency additionally causes neurological features and elevated homocysteine AND methylmalonic acid. "
      "Folate deficiency: Only elevated homocysteine (not methylmalonic acid). "
      "(Lippincott 8th Ed; Robbins Pathology)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 42,
  "year": "INICET Nov 2021",
  "q": "Homocystinuria due to cystathionine beta-synthase deficiency is treated with which vitamin?",
  "opts": [
      "A. Vitamin B12",
      "B. Vitamin B6 (Pyridoxine)",
      "C. Folic acid",
      "D. Riboflavin"
  ],
  "ans": "B",
  "exp": (
      "Homocystinuria (classic type): Cystathionine beta-synthase (CBS) deficiency -> homocysteine accumulates. "
      "Inheritance: Autosomal recessive. "
      "Features: Intellectual disability, lens dislocation (DOWNWARD, ectopia lentis), Marfanoid habitus, "
      "osteoporosis, THROMBOEMBOLISM (platelet aggregation + vascular endothelial injury). "
      "Biochemistry: Methionine -> Homocysteine -> (CBS, PLP/B6) -> Cystathionine -> Cysteine. "
      "If CBS defective -> Homocysteine accumulates. "
      "Treatment: Vitamin B6 (B6-responsive variant); also methionine-restricted diet + betaine supplementation. "
      "B12 + Folate also lower homocysteine (via methionine synthase remethylation pathway). "
      "Elevated homocysteine is also a CARDIOVASCULAR RISK FACTOR (damages endothelium). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 43,
  "year": "NEET PG 2021",
  "q": "Which enzyme is deficient in Tay-Sachs disease?",
  "opts": [
      "A. Glucocerebrosidase",
      "B. Sphingomyelinase",
      "C. Hexosaminidase A",
      "D. Arylsulfatase A"
  ],
  "ans": "C",
  "exp": (
      "LYSOSOMAL STORAGE DISEASES - HIGH YIELD TABLE: "
      "- Tay-Sachs: Hexosaminidase A deficiency -> GM2 ganglioside accumulation; "
      "  cherry-red spot on macula, progressive neurodegeneration; no organomegaly; AR. "
      "- Gaucher disease: Glucocerebrosidase (beta-glucosidase) deficiency -> glucocerebroside; "
      "  most common LSD; Gaucher cells (crumpled tissue paper cytoplasm); hepatosplenomegaly, bone pain. "
      "- Niemann-Pick: Sphingomyelinase deficiency -> sphingomyelin; cherry-red spot + hepatosplenomegaly. "
      "- Krabbe: Galactocerebrosidase deficiency; globoid cells. "
      "- Metachromatic leukodystrophy (MLD): Arylsulfatase A deficiency. "
      "- Fabry: Alpha-galactosidase A deficiency; X-linked; angiokeratoma, renal failure. "
      "- Hurler: Alpha-L-iduronidase (MPS type I); corneal clouding + intellectual disability. "
      "(Lippincott 8th Ed; Robbins Pathology)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 44,
  "year": "INICET May 2023",
  "q": "The P450 cytochrome enzyme system in drug metabolism primarily uses which cofactor?",
  "opts": [
      "A. NAD+",
      "B. FAD",
      "C. NADPH",
      "D. FMN"
  ],
  "ans": "C",
  "exp": (
      "Cytochrome P450 (CYP) monooxygenase system: "
      "CYP enzymes catalyze: R-H + O2 + NADPH + H+ -> R-OH + H2O + NADP+ "
      "Electron donor: NADPH (via NADPH-cytochrome P450 reductase, which uses both FAD and FMN). "
      "Location: Mainly ER (microsomes) and mitochondria of LIVER (also intestine, lung, adrenal). "
      "Functions: Drug/xenobiotic metabolism (Phase I - oxidation, hydroxylation), "
      "steroid hormone synthesis, vitamin D activation, fatty acid omega-oxidation. "
      "Important CYP inducers: Rifampicin, carbamazepine, phenytoin, barbiturates (St. John's Wort). "
      "Important CYP inhibitors: Ketoconazole, erythromycin, grapefruit juice (CYP3A4), isoniazid (CYP2E1). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 45,
  "year": "NEET PG 2022",
  "q": "Southern blotting detects:",
  "opts": [
      "A. RNA",
      "B. Protein",
      "C. DNA",
      "D. Lipids"
  ],
  "ans": "C",
  "exp": (
      "BLOTTING TECHNIQUES MNEMONIC (SDN-WEB): "
      "S = Southern blot -> DNA (invented by Edwin Southern, 1975) "
      "N = Northern blot -> RNA (mRNA/gene expression) "
      "W = Western blot -> Protein (e.g., HIV confirmatory test - detects anti-HIV antibodies/viral proteins) "
      "Other techniques: "
      "- ELISA: Antigen or antibody detection (HIV screening) "
      "- PCR: Amplifies specific DNA sequences (most sensitive diagnostic tool) "
      "- FISH (Fluorescence In Situ Hybridization): Chromosomal abnormalities "
      "- DNA microarray / gene chip: Genome-wide expression profiling "
      "Southern blot steps: Restriction enzyme digest -> agarose gel electrophoresis -> "
      "transfer to nitrocellulose membrane -> hybridization with labeled probe -> detection. "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 46,
  "year": "INICET Nov 2022",
  "q": "Which mutation causes sickle cell disease?",
  "opts": [
      "A. Deletion of exon 1 of beta-globin gene",
      "B. Point mutation: Glu -> Val at position 6 of beta-globin chain",
      "C. Frameshift mutation in alpha-globin gene",
      "D. Nonsense mutation causing premature stop codon at position 17"
  ],
  "ans": "B",
  "exp": (
      "Sickle Cell Disease: Single POINT MUTATION in HBB gene (beta-globin). "
      "Codon 6: GAG -> GTG (A->T transversion) = Glutamic acid (Glu, negatively charged) -> Valine (Val, hydrophobic). "
      "This substitution creates a hydrophobic 'sticky patch' on deoxygenated HbS -> "
      "HbS polymerizes into long fibers -> RBC sickling. "
      "Inheritance: Autosomal recessive; HbSS = disease; HbAS = sickle cell trait (mostly asymptomatic). "
      "HbF (fetal Hb, alpha2-gamma2) inhibits sickling - hence hydroxyurea (increases HbF) is therapeutic. "
      "Lab: HbS migrates differently on hemoglobin electrophoresis (alkaline: HbS between HbA and HbC). "
      "Complications: Vaso-occlusive crisis, acute chest syndrome, splenic sequestration/autosplenectomy, "
      "stroke, priapism, avascular necrosis, aplastic crisis (parvovirus B19). "
      "(Lippincott 8th Ed; Harrison's 22E)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 47,
  "year": "NEET PG 2021",
  "q": "Which enzyme catalyzes the conversion of fibrinogen to fibrin?",
  "opts": [
      "A. Plasmin",
      "B. Thrombin",
      "C. Factor Xa",
      "D. Streptokinase"
  ],
  "ans": "B",
  "exp": (
      "THROMBIN (Factor IIa): Serine protease that cleaves fibrinogen (Factor I) -> fibrin monomers. "
      "Fibrin monomers -> (Factor XIIIa cross-links) -> stable fibrin clot. "
      "Thrombin also: Activates Factors V, VIII, XI, XIII; activates platelets; activates Protein C "
      "(anticoagulant when bound to thrombomodulin). "
      "Plasmin: Fibrinolytic enzyme; cleaves fibrin -> FDPs; D-dimer is a specific FDP. "
      "Streptokinase: Bacterial protein that activates plasminogen -> plasmin (thrombolytic agent). "
      "Direct thrombin inhibitors: Dabigatran (oral), argatroban, bivalirudin. "
      "LMWH/Heparin: Enhances antithrombin (inhibits Xa and IIa). "
      "(Lippincott 8th Ed)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 48,
  "year": "INICET May 2023",
  "q": "GLUT-2 transporter is characteristically found in which tissue?",
  "opts": [
      "A. Brain and neurons",
      "B. Liver, pancreatic beta-cells, and small intestine",
      "C. Muscle and adipose tissue",
      "D. RBCs only"
  ],
  "ans": "B",
  "exp": (
      "GLUCOSE TRANSPORTERS (GLUTs) - HIGH YIELD: "
      "GLUT-1: RBCs, blood-brain barrier; high affinity (low Km); basal glucose uptake. "
      "GLUT-2: LIVER, PANCREATIC BETA-CELLS, small intestine, kidney; LOW affinity (high Km ~15-20 mM); "
      "  acts as glucose SENSOR - active only when blood glucose is HIGH (postprandial). "
      "GLUT-3: Neurons; high affinity (even in low glucose). "
      "GLUT-4: MUSCLE and ADIPOSE; insulin-dependent (translocated to membrane by insulin via Akt pathway); "
      "  exercise also causes GLUT-4 translocation independently of insulin. "
      "GLUT-5: Fructose transporter in small intestine and sperm. "
      "SGLTs (Na+-glucose cotransporters): SGLT1 (intestine, kidney S3), SGLT2 (kidney S1/S2, proximal tubule). "
      "SGLT2 inhibitors (e.g. empagliflozin) used in T2DM. "
      "(Basic Medical Biochemistry 6e; Lippincott 8th Ed)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 49,
  "year": "NEET PG 2023",
  "q": "The process of removing introns and joining exons during gene expression is called:",
  "opts": [
      "A. Translation",
      "B. Transcription",
      "C. RNA splicing",
      "D. RNA capping"
  ],
  "ans": "C",
  "exp": (
      "Post-transcriptional modifications of pre-mRNA in eukaryotes: "
      "1. 5' CAPPING: Addition of 7-methylguanosine cap -> protects mRNA from degradation, aids ribosomal binding. "
      "2. 3' POLYADENYLATION: Poly-A tail added by poly-A polymerase -> stability, nuclear export. "
      "3. RNA SPLICING: Removal of INTRONS, joining of EXONS; carried out by SPLICEOSOME "
      "   (snRNPs - small nuclear ribonucleoproteins: U1, U2, U4, U5, U6). "
      "   Branch point A nucleotide attacks 5' splice site (transesterification). "
      "Alternative splicing: One pre-mRNA can generate multiple different proteins -> proteome diversity. "
      "Splicing mutations: Can cause disease (e.g., beta-thalassemia - some mutations affect splice sites). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
{
  "section": "Additional High-Yield MCQs",
  "no": 50,
  "year": "INICET Nov 2022",
  "q": "Which amino acid is the immediate precursor of NO (nitric oxide) synthesis?",
  "opts": [
      "A. Glutamine",
      "B. Arginine",
      "C. Citrulline",
      "D. Aspartate"
  ],
  "ans": "B",
  "exp": (
      "Nitric Oxide (NO) synthesis: "
      "L-ARGININE + O2 + NADPH -> (Nitric Oxide Synthase, NOS) -> L-CITRULLINE + NO. "
      "Cofactors for NOS: NADPH, FAD, FMN, BH4, calmodulin/Ca2+. "
      "Three isoforms of NOS: "
      "- eNOS (endothelial): Vasodilation (activated by Ca2+/shear stress); NO -> cGMP -> PKG -> MLCK inhibition. "
      "- nNOS (neuronal): Neurotransmission; memory (LTP). "
      "- iNOS (inducible): Macrophages; immune defense; large amounts of NO -> cytotoxic. "
      "Pharmacology: Nitrates (GTN, isosorbide) -> NO donors; sildenafil inhibits PDE5 (prevents cGMP breakdown). "
      "L-NMMA and L-NAME are NOS inhibitors (used experimentally). "
      "(Lippincott 8th Ed; Harper's 32nd Ed)"
  )
},
]

# ─── PDF GENERATION ────────────────────────────────────────────────────────────
def build_pdf():
    doc = SimpleDocTemplate(
        OUTPUT_PATH,
        pagesize=A4,
        rightMargin=2*cm, leftMargin=2*cm,
        topMargin=2.5*cm, bottomMargin=2*cm,
        title="Biochemistry NEET PG / INICET High Yield PYQs",
        author="Orris Medical AI"
    )

    styles = getSampleStyleSheet()

    # Custom styles
    cover_title = ParagraphStyle(
        "CoverTitle",
        parent=styles["Title"],
        fontSize=26,
        textColor=colors.HexColor("#1a3a5c"),
        spaceAfter=10,
        alignment=TA_CENTER,
        fontName="Helvetica-Bold"
    )
    cover_sub = ParagraphStyle(
        "CoverSub",
        parent=styles["Normal"],
        fontSize=13,
        textColor=colors.HexColor("#2e6da4"),
        spaceAfter=6,
        alignment=TA_CENTER
    )
    section_heading = ParagraphStyle(
        "SectionHeading",
        parent=styles["Heading1"],
        fontSize=14,
        textColor=colors.white,
        backColor=colors.HexColor("#1a3a5c"),
        spaceBefore=14,
        spaceAfter=8,
        leftIndent=-10,
        rightIndent=-10,
        borderPadding=(6, 8, 6, 8),
        fontName="Helvetica-Bold"
    )
    q_no_style = ParagraphStyle(
        "QNo",
        parent=styles["Normal"],
        fontSize=9,
        textColor=colors.HexColor("#2e6da4"),
        spaceAfter=2,
        fontName="Helvetica-Bold"
    )
    q_style = ParagraphStyle(
        "QText",
        parent=styles["Normal"],
        fontSize=11,
        textColor=colors.HexColor("#1a1a1a"),
        spaceAfter=4,
        leading=16,
        fontName="Helvetica-Bold"
    )
    opt_style = ParagraphStyle(
        "OptText",
        parent=styles["Normal"],
        fontSize=10,
        textColor=colors.HexColor("#333333"),
        leading=15,
        leftIndent=10
    )
    ans_style = ParagraphStyle(
        "AnsText",
        parent=styles["Normal"],
        fontSize=10,
        textColor=colors.HexColor("#1a7a2e"),
        spaceAfter=3,
        fontName="Helvetica-Bold"
    )
    exp_style = ParagraphStyle(
        "ExpText",
        parent=styles["Normal"],
        fontSize=9.5,
        textColor=colors.HexColor("#2a2a2a"),
        leading=14.5,
        spaceAfter=4,
        alignment=TA_JUSTIFY
    )
    tag_style = ParagraphStyle(
        "TagStyle",
        parent=styles["Normal"],
        fontSize=8.5,
        textColor=colors.HexColor("#666666"),
        spaceAfter=2,
        fontName="Helvetica-Oblique"
    )
    footer_style = ParagraphStyle(
        "Footer",
        parent=styles["Normal"],
        fontSize=8,
        textColor=colors.grey,
        alignment=TA_CENTER
    )

    story = []

    # ── COVER PAGE ──────────────────────────────────────────────────────────────
    story.append(Spacer(1, 1.5*cm))
    story.append(Paragraph("BIOCHEMISTRY", cover_title))
    story.append(Paragraph("NEET PG &amp; INICET", cover_title))
    story.append(Spacer(1, 0.5*cm))
    story.append(Paragraph("High Yield Previous Year Questions (PYQs)", cover_sub))
    story.append(Paragraph("with Detailed Explanations", cover_sub))
    story.append(Spacer(1, 0.3*cm))
    story.append(HRFlowable(width="100%", thickness=2, color=colors.HexColor("#2e6da4")))
    story.append(Spacer(1, 0.3*cm))

    stats_data = [
        ["Total Questions", "Exam Coverage", "Topics", "Compiled"],
        ["50 MCQs", "NEET PG 2019-2024\nINICET 2021-2023", "10 Core Topics", "June 2026"]
    ]
    stats_table = Table(stats_data, colWidths=[4*cm, 5.5*cm, 4*cm, 4*cm])
    stats_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), colors.HexColor("#1a3a5c")),
        ("TEXTCOLOR", (0,0), (-1,0), colors.white),
        ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"),
        ("FONTSIZE", (0,0), (-1,0), 10),
        ("FONTSIZE", (0,1), (-1,1), 10),
        ("ALIGN", (0,0), (-1,-1), "CENTER"),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("ROWBACKGROUNDS", (0,1), (-1,1), [colors.HexColor("#e8f0fb")]),
        ("GRID", (0,0), (-1,-1), 0.5, colors.HexColor("#2e6da4")),
        ("TOPPADDING", (0,0), (-1,-1), 8),
        ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ]))
    story.append(stats_table)
    story.append(Spacer(1, 0.5*cm))

    topics_header = ParagraphStyle("TH", parent=styles["Normal"], fontSize=11,
                                   fontName="Helvetica-Bold", textColor=colors.HexColor("#1a3a5c"),
                                   spaceBefore=8, spaceAfter=4)
    story.append(Paragraph("Topics Covered:", topics_header))
    topics_list = [
        "1. Enzyme Kinetics & Regulation (Km, Vmax, inhibition, allosteric)",
        "2. Carbohydrate Metabolism (Glycolysis, GSD, G6PD, HbA1c, gluconeogenesis)",
        "3. Lipid Metabolism (Cholesterol, Lipoprotein, Ketogenesis, FA synthesis)",
        "4. Protein & Amino Acid Metabolism (PKU, Alkaptonuria, Urea cycle, MSUD)",
        "5. Vitamins & Cofactors (B1, B3, B6, B7, B12, C, K)",
        "6. Nucleotide Metabolism & Molecular Biology (Gout, DNA replication, PCR, blotting)",
        "7. TCA Cycle & Oxidative Phosphorylation (ETC inhibitors, ATP yield)",
        "8. Heme Synthesis & Porphyrias (ALA synthase, Porphyrias, Lead poisoning)",
        "9. Connective Tissue & Structural Proteins (Collagen types, Marfan, EDS)",
        "10. Hormones, Signal Transduction & Clinical Biochemistry (cAMP/IP3, RAAS, GLUTs)"
    ]
    for t in topics_list:
        story.append(Paragraph(t, ParagraphStyle("TL", parent=styles["Normal"], fontSize=10,
                                                  leftIndent=10, spaceAfter=3,
                                                  textColor=colors.HexColor("#2a2a2a"))))

    story.append(Spacer(1, 0.5*cm))
    story.append(HRFlowable(width="100%", thickness=1, color=colors.HexColor("#2e6da4")))
    story.append(Spacer(1, 0.3*cm))
    story.append(Paragraph(
        "Sources: Harper's Illustrated Biochemistry 32nd Ed | Lippincott Biochemistry 8th Ed | "
        "Basic Medical Biochemistry 6e | Harrison's 22E | Robbins Basic Pathology",
        ParagraphStyle("Src", parent=styles["Normal"], fontSize=8.5, textColor=colors.grey,
                       alignment=TA_CENTER, fontName="Helvetica-Oblique")))
    story.append(PageBreak())

    # ── QUESTIONS ──────────────────────────────────────────────────────────────
    current_section = None
    for q in questions:
        if q["section"] != current_section:
            current_section = q["section"]
            story.append(Spacer(1, 0.4*cm))
            # Section header with colored background
            sec_table = Table([[Paragraph(f"  {current_section}", section_heading)]],
                              colWidths=[17*cm])
            sec_table.setStyle(TableStyle([
                ("BACKGROUND", (0,0), (-1,-1), colors.HexColor("#1a3a5c")),
                ("TOPPADDING", (0,0), (-1,-1), 5),
                ("BOTTOMPADDING", (0,0), (-1,-1), 5),
                ("LEFTPADDING", (0,0), (-1,-1), 8),
            ]))
            story.append(sec_table)
            story.append(Spacer(1, 0.3*cm))

        # Build question block
        q_block = []
        q_block.append(Paragraph(
            f"Q{q['no']}. <font color='#2e6da4'>({q['year']})</font>",
            q_no_style))
        q_block.append(Paragraph(q["q"], q_style))
        for opt in q["opts"]:
            q_block.append(Paragraph(opt, opt_style))
        q_block.append(Spacer(1, 0.15*cm))

        # Answer row
        ans_table = Table(
            [[Paragraph(f"ANSWER: {q['ans']}", ans_style),
              Paragraph("", styles["Normal"])]],
            colWidths=[3.5*cm, 13.5*cm]
        )
        ans_table.setStyle(TableStyle([
            ("BACKGROUND", (0,0), (-1,-1), colors.HexColor("#e8f8ed")),
            ("LEFTPADDING", (0,0), (-1,-1), 6),
            ("RIGHTPADDING", (0,0), (-1,-1), 6),
            ("TOPPADDING", (0,0), (-1,-1), 4),
            ("BOTTOMPADDING", (0,0), (-1,-1), 4),
            ("ROUNDEDCORNERS", [3]),
        ]))
        q_block.append(ans_table)
        q_block.append(Spacer(1, 0.1*cm))

        # Explanation
        exp_box = Table(
            [[Paragraph("<b>Explanation:</b>", ParagraphStyle("ExpH", parent=styles["Normal"],
                                                               fontSize=9.5, fontName="Helvetica-Bold",
                                                               textColor=colors.HexColor("#1a3a5c")))],
             [Paragraph(q["exp"], exp_style)]],
            colWidths=[17*cm]
        )
        exp_box.setStyle(TableStyle([
            ("BACKGROUND", (0,0), (-1,-1), colors.HexColor("#f5f8fd")),
            ("BOX", (0,0), (-1,-1), 0.75, colors.HexColor("#2e6da4")),
            ("LEFTPADDING", (0,0), (-1,-1), 8),
            ("RIGHTPADDING", (0,0), (-1,-1), 8),
            ("TOPPADDING", (0,0), (-1,-1), 5),
            ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ]))
        q_block.append(exp_box)
        q_block.append(Spacer(1, 0.4*cm))
        q_block.append(HRFlowable(width="100%", thickness=0.5, color=colors.HexColor("#cccccc")))
        q_block.append(Spacer(1, 0.2*cm))

        story.append(KeepTogether(q_block))

    # ── END NOTES ───────────────────────────────────────────────────────────────
    story.append(PageBreak())
    story.append(Spacer(1, 1*cm))
    end_title = ParagraphStyle("ET", parent=styles["Normal"], fontSize=16,
                               fontName="Helvetica-Bold", textColor=colors.HexColor("#1a3a5c"),
                               alignment=TA_CENTER, spaceAfter=12)
    story.append(Paragraph("Quick Reference Summary", end_title))
    story.append(HRFlowable(width="100%", thickness=2, color=colors.HexColor("#2e6da4")))
    story.append(Spacer(1, 0.5*cm))

    summary_data = [
        ["Topic", "Rate-Limiting Enzyme / Key Fact"],
        ["Glycolysis", "PFK-1 (activated by AMP, fructose-2,6-BP; inhibited by ATP, citrate)"],
        ["Gluconeogenesis", "Fructose-1,6-bisphosphatase (inhibited by AMP, F-2,6-BP)"],
        ["Fatty Acid Synthesis", "Acetyl-CoA Carboxylase (inhibited by palmitoyl-CoA; activated by citrate)"],
        ["Beta-Oxidation", "Carnitine shuttle via CPT-I (inhibited by malonyl-CoA)"],
        ["Ketogenesis", "HMG-CoA synthase (mitochondrial); only in hepatic mitochondria"],
        ["Cholesterol Synthesis", "HMG-CoA Reductase (inhibited by statins)"],
        ["Heme Synthesis", "ALA Synthase (inhibited by heme; cofactor PLP/B6)"],
        ["Urea Cycle", "CPS-I (carbamoyl phosphate synthetase I) - first committed step"],
        ["Purine Synthesis (de novo)", "PRPP amidotransferase (rate-limiting; inhibited by AMP/GMP)"],
        ["Pyrimidine Synthesis", "CPS-II (cytoplasm) / ATCase"],
        ["TCA Cycle", "Isocitrate dehydrogenase (key regulatory enzyme)"],
    ]

    summary_table = Table(summary_data, colWidths=[5.5*cm, 11.5*cm])
    summary_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), colors.HexColor("#1a3a5c")),
        ("TEXTCOLOR", (0,0), (-1,0), colors.white),
        ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"),
        ("FONTSIZE", (0,0), (-1,-1), 9),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [colors.white, colors.HexColor("#e8f0fb")]),
        ("GRID", (0,0), (-1,-1), 0.5, colors.HexColor("#2e6da4")),
        ("TOPPADDING", (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING", (0,0), (-1,-1), 6),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ]))
    story.append(summary_table)
    story.append(Spacer(1, 1*cm))

    disclaimer_style = ParagraphStyle("Disc", parent=styles["Normal"], fontSize=8,
                                      textColor=colors.grey, alignment=TA_CENTER,
                                      fontName="Helvetica-Oblique")
    story.append(Paragraph(
        "This material is compiled for educational purposes from authoritative medical textbooks "
        "(Harper's 32nd Ed, Lippincott Biochemistry 8th Ed, Basic Medical Biochemistry 6e, Harrison's 22E). "
        "Always cross-reference with your institution's recommended curriculum. | Generated by Orris Medical AI | June 2026",
        disclaimer_style))

    doc.build(story)
    print(f"PDF saved to: {OUTPUT_PATH}")

if __name__ == "__main__":
    build_pdf()