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Here is your complete NEET PG guide on Metabolic Pathways, compiled from Lippincott Illustrated Reviews: Biochemistry and Harper's Illustrated Biochemistry.

🧬 Metabolic Pathways - NEET PG Complete Guide

1. GLYCOLYSIS

Glycolysis - Aerobic and Anaerobic pathways

Figure: A = Glycolysis as hub of carbohydrate metabolism | B = Aerobic glycolysis | C = Anaerobic glycolysis

Overview

Location: Cytosol (all tissues)
10 reactions converting glucose → pyruvate
Aerobic glycolysis: O₂ required to reoxidize NADH → pyruvate is end product
Anaerobic glycolysis: No O₂ needed → glucose → lactate (occurs in RBCs, parts of eye, hypoxic cells)

GLUT Transporters (HIGH-YIELD for NEET PG)

GLUT	Location	Key Feature
GLUT-1	Most tissues, RBCs, brain	Basal glucose uptake
GLUT-2	Liver, kidney, pancreatic β-cells	High Km (glucose sensor)
GLUT-3	Brain neurons	High affinity
GLUT-4	Muscle, adipose	Insulin-dependent
GLUT-5	Small intestine	Fructose transporter

Key Enzymes & Regulatory Steps

Three irreversible (regulated) steps:

Step	Enzyme	Regulator
Glucose → Glucose-6-P	Hexokinase (tissues) / Glucokinase (liver, β-cells)	Inhibited by G-6-P (hexokinase only)
Fructose-6-P → Fructose-1,6-bisP	Phosphofructokinase-1 (PFK-1) - RATE LIMITING	Activated by AMP, F-2,6-bisP; Inhibited by ATP, citrate
PEP → Pyruvate	Pyruvate kinase	Activated by F-1,6-bisP; Inhibited by ATP, alanine

ATP Yield

Aerobic glycolysis (1 glucose): Net 2 ATP + 2 NADH + 2 pyruvate
Anaerobic glycolysis: Net 2 ATP only (no NADH benefit)

Warburg Effect (NEET PG Favourite!)

Cancer cells use anaerobic glycolysis even in presence of O₂
Reason: Rapid ATP generation + biosynthetic precursor supply

2. TCA CYCLE (Krebs / Citric Acid Cycle)

Figure: Citric acid cycle linked to the respiratory chain and oxidative phosphorylation

Overview

Location: Mitochondrial matrix
Acetyl-CoA (C2) + Oxaloacetate (C4) → Citrate (C6) → regenerates OAA
2 CO₂ released per turn
Main pathway for ATP generation

Steps & Key Enzymes

Reaction	Enzyme	Cofactor/Notes
Acetyl-CoA + OAA → Citrate	Citrate synthase	Inhibited by NADH, succinyl-CoA
Citrate → Isocitrate	Aconitase	Contains iron-sulfur cluster
Isocitrate → α-Ketoglutarate	Isocitrate dehydrogenase	Releases CO₂; NAD⁺ → NADH
α-KG → Succinyl-CoA	α-KG dehydrogenase	Releases CO₂; similar to PDH; needs TPP, lipoate, FAD, NAD⁺, CoA
Succinyl-CoA → Succinate	Succinyl-CoA synthetase	GTP formed (substrate-level phosphorylation)
Succinate → Fumarate	Succinate dehydrogenase	Uses FAD (Complex II); inhibited by malonate
Fumarate → Malate	Fumarase	—
Malate → OAA	Malate dehydrogenase	NAD⁺ → NADH

ATP Yield Per Turn

3 NADH → 7.5 ATP (at 2.5 ATP/NADH)
1 FADH₂ → 1.5 ATP
1 GTP → 1 ATP
Total = 10 ATP per acetyl-CoA
Per glucose (2 acetyl-CoA): 20 ATP from TCA alone

Anaplerosis vs. Cataplerosis

Anaplerosis - feeding intermediates INTO the cycle (e.g., pyruvate → OAA via pyruvate carboxylase)
Cataplerosis - removing intermediates OUT of the cycle (e.g., OAA → PEP for gluconeogenesis)

Vitamins in TCA Cycle

Mnemonic: "The Lovely Nurse For Biochem"

Thiamine (B1) - α-KG dehydrogenase, PDH
Lipoic acid - α-KG dehydrogenase, PDH
Niacin (B3, NAD⁺) - multiple dehydrogenases
Flavin (B2, FAD) - succinate dehydrogenase, PDH
Biotin (B7) - pyruvate carboxylase (anaplerosis)

3. PYRUVATE DEHYDROGENASE COMPLEX (PDH)

Overview

Converts pyruvate → Acetyl-CoA + CO₂ (irreversible!)
Location: Mitochondrial matrix
Links glycolysis to TCA cycle

Cofactors (NEET PG HIGH-YIELD)

Mnemonic: "Tender Loving Care For Nerves"

TPP (Thiamine pyrophosphate) - Vit B1
Lipoic acid
CoA (pantothenic acid, Vit B5)
FAD (riboflavin, Vit B2)
NAD⁺ (niacin, Vit B3)

Regulation

Activated by	Inhibited by
AMP, CoA, NAD⁺, Ca²⁺	ATP, acetyl-CoA, NADH, fatty acids
PDH phosphatase (insulin activates)	PDH kinase (phosphorylation inactivates)

Clinical Pearl

Thiamine (B1) deficiency → PDH block → pyruvate accumulates → converted to lactate (lactic acidosis) or alanine
Seen in: Wernicke's encephalopathy, Beriberi, alcoholism

4. GLUCONEOGENESIS

Overview

Synthesis of glucose from non-carbohydrate precursors
Location: Mainly liver (90%), kidney (10%); during prolonged fasting, kidney contributes ~40%
Occurs when liver glycogen is depleted (<24 hrs fasting)

Substrates (Gluconeogenic Precursors)

Lactate - via Cori cycle (muscle → liver)
Glycerol - from TAG hydrolysis in adipose tissue
Glucogenic amino acids - ALL except leucine and lysine (purely ketogenic)
Propionate - from odd-chain fatty acid oxidation

Cori Cycle (HIGH-YIELD)

Muscle: Glucose → Lactate (anaerobic glycolysis)
Liver: Lactate → Glucose (gluconeogenesis)
Net energy cost: 4 ATP equivalents per cycle (liver does the expensive work)

Unique Enzymes of Gluconeogenesis (bypass irreversible glycolytic steps)

Bypassed step	Gluconeogenic enzyme	Location
Pyruvate → PEP	Pyruvate carboxylase (pyruvate → OAA) + PEPCK (OAA → PEP)	PC in mitochondria; PEPCK in cytosol
F-1,6-bisP → F-6-P	Fructose-1,6-bisphosphatase	Cytosol
G-6-P → Glucose	Glucose-6-phosphatase	ER (liver/kidney only)

Regulation

Activated by: Glucagon, cortisol, fasting
Inhibited by: Insulin, AMP, F-2,6-bisphosphate

Reciprocal Regulation with Glycolysis

Molecule	Glycolysis	Gluconeogenesis
Insulin	↑	↓
Glucagon	↓	↑
F-2,6-bisP	↑ (PFK-1)	↓ (F-1,6-bisP-ase)
AMP	↑	↓

5. GLYCOGEN METABOLISM

Glycogen Synthesis

Glucose-1-P → UDP-glucose (by UDP-glucose pyrophosphorylase)
Glycogen synthase adds glucose to chain (α-1,4 linkage)
Branching enzyme creates α-1,6 branches

Glycogen Breakdown

Glycogen phosphorylase cleaves α-1,4 bonds → Glucose-1-P
Debranching enzyme handles α-1,6 branch points → free glucose

Regulation

	Liver	Muscle
Purpose	Blood glucose maintenance	Fuel for muscle itself
Stimulated by	Glucagon, epinephrine	Epinephrine, Ca²⁺, AMP
Inhibited by	Insulin, glucose	Insulin

Glycogen Storage Diseases (NEET PG FAVOURITE!)

Disease	Enzyme Deficiency	Affected Organ	Key Feature
Von Gierke (Type I)	Glucose-6-phosphatase	Liver, kidney	Hypoglycemia, lactic acidosis, hepatomegaly
Pompe (Type II)	Lysosomal α-1,4-glucosidase (acid maltase)	Heart, muscle	Cardiomegaly, hypotonia; ONLY lysosomal
Cori (Type III)	Debranching enzyme	Liver, muscle	Milder Von Gierke-like
Anderson (Type IV)	Branching enzyme	Liver	Cirrhosis
McArdle (Type V)	Muscle phosphorylase	Muscle	Painful cramps, no lactate rise with exercise
Hers (Type VI)	Liver phosphorylase	Liver	Mild hypoglycemia

6. HMP SHUNT (Pentose Phosphate Pathway)

Overview

Location: Cytosol
Main products: NADPH + Ribose-5-phosphate
Does NOT produce ATP directly
Active in: Liver, RBCs, adrenal cortex, mammary glands, testes

Two Phases

Oxidative phase (irreversible):

Glucose-6-P → Ribulose-5-P
2 NADPH generated
Rate-limiting enzyme: Glucose-6-phosphate dehydrogenase (G6PD)

Non-oxidative phase (reversible):

Interconverts sugar phosphates
Key enzymes: Transketolase (needs Thiamine/TPP), transaldolase

Functions of NADPH

Antioxidant defense - regenerates glutathione (protects RBCs)
Fatty acid synthesis
Cholesterol synthesis
Cytochrome P450 reactions
Respiratory burst in neutrophils (NADPH oxidase)

G6PD Deficiency (HIGH-YIELD!)

X-linked; most common enzyme deficiency worldwide
Triggers: Primaquine, dapsone, sulfonamides, fava beans, infections
Result: RBC hemolysis (Heinz bodies, bite cells on smear)
Mechanism: ↓ NADPH → ↓ reduced glutathione → oxidative damage to RBCs

7. FATTY ACID METABOLISM

Beta-Oxidation

Location: Mitochondrial matrix
Carnitine shuttle required to move long-chain fatty acids across inner mitochondrial membrane
Carnitine palmitoyltransferase I (CPT-I): Rate-limiting step; inhibited by malonyl-CoA

ATP Yield (Palmitate C16)

7 cycles of beta-oxidation → 8 acetyl-CoA + 7 FADH₂ + 7 NADH
Total ATP ≈ 106 ATP (net ~129 ATP gross - 2 for activation)

Ketone Body Synthesis (Ketogenesis)

Location: Liver mitochondria (only synthesis; liver CANNOT use them)
Occurs during: Fasting, starvation, uncontrolled diabetes (Type 1)
Products: Acetoacetate, β-hydroxybutyrate, acetone
Rate-limiting enzyme: HMG-CoA synthase

Ketone Body Utilization

Used by: Brain (prolonged fasting), heart, skeletal muscle, kidney
NOT by liver (lacks succinyl-CoA transferase/thiophorase)

8. UREA CYCLE

Overview

Converts toxic ammonia → urea (for excretion)
Location: Liver (mitochondria + cytosol)
First 2 steps in mitochondria; rest in cytosol

Steps (Mnemonic: "Clever Argonauts Carry Argonauts Free")

NH₃ + CO₂ → Carbamoyl phosphate (CPS-I, mitochondria; needs N-acetylglutamate)
Carbamoyl-P + Ornithine → Citrulline (enters cytosol)
Citrulline + Aspartate → Argininosuccinate
Argininosuccinate → Arginine + Fumarate
Arginine → Ornithine + Urea (arginase)

Clinical Pearl

N-acetylglutamate is the essential activator of CPS-I
Hyperammonemia → cerebral edema, asterixis, encephalopathy
Treatment: Lactulose, low-protein diet, sodium benzoate

9. OXIDATIVE PHOSPHORYLATION & ETC

Electron Transport Chain Complexes

Complex	Name	Electron carrier	Inhibitor
I	NADH dehydrogenase	NADH → CoQ	Rotenone, amobarbital
II	Succinate dehydrogenase	FADH₂ → CoQ	Malonate
III	CoQ-cytochrome c reductase	CoQ → Cyt c	Antimycin A
IV	Cytochrome c oxidase	Cyt c → O₂	Cyanide, CO, azide
V	ATP synthase	H⁺ gradient → ATP	Oligomycin

Uncouplers

Dissipate proton gradient without making ATP → heat produced
Examples: DNP (2,4-dinitrophenol), thermogenin (brown adipose UCP-1), aspirin (overdose)

ATP Yield Summary (1 glucose, complete oxidation)

Stage	ATP
Glycolysis	2 (net)
Pyruvate decarboxylation (×2)	5
TCA cycle (×2)	20
Oxidative phosphorylation (from NADH/FADH₂)	~3-4
TOTAL	~30-32 ATP

10. QUICK REVISION - RATE-LIMITING ENZYMES

Pathway	Rate-Limiting Enzyme
Glycolysis	PFK-1
TCA cycle	Isocitrate dehydrogenase
Gluconeogenesis	PEPCK (or pyruvate carboxylase)
Glycogen synthesis	Glycogen synthase
Glycogenolysis	Glycogen phosphorylase
Fatty acid synthesis	Acetyl-CoA carboxylase (ACC)
Beta-oxidation	CPT-I (carnitine shuttle)
Ketogenesis	HMG-CoA synthase
HMP shunt	G6PD
Cholesterol synthesis	HMG-CoA reductase
Urea cycle	CPS-I

11. IMPORTANT CONNECTIONS (Integration)

Glucose
  ↓ Glycolysis
Pyruvate ──(PDH)──→ Acetyl-CoA ──→ TCA Cycle ──→ ATP
  ↑                      ↓
Gluconeogenesis      Ketone bodies (in liver)
  ↑                      ↓
Lactate, AA,         Lipid synthesis
Glycerol             (if excess)

Insulin: ↑ Glycolysis, ↑ Glycogen synthesis, ↑ FA synthesis, ↓ Gluconeogenesis
Glucagon: ↑ Gluconeogenesis, ↑ Glycogenolysis, ↑ Ketogenesis, ↓ Glycolysis
F-2,6-bisphosphate: Master regulator - ↑ PFK-1 (glycolysis) and ↓ FBPase-1 (gluconeogenesis)

NEET PG EXAM TIPS

One-way reactions to remember: PDH (pyruvate → acetyl-CoA is irreversible - why fat can't make glucose)
Only purely ketogenic AAs: Leucine & Lysine (LL - no gluconeogenesis)
G6Pase absent in muscle - muscle glycogen cannot contribute to blood glucose
Liver vs Muscle glucokinase vs hexokinase - always a MCQ
Pompe disease = only lysosomal GSD - associated with cardiomegaly
McArdle = no lactate rise with ischemic exercise test
Cyanide poisoning = inhibits Complex IV = cells cannot use O₂ = histotoxic hypoxia
Thiamine deficiency affects 3 enzymes: PDH, α-KG dehydrogenase, Transketolase

Sources: Lippincott Illustrated Reviews: Biochemistry 8e; Harper's Illustrated Biochemistry 32e

Create a presentation on metabolic pathways for quick revision

Reading File

Running Command

mkdir -p /home/daytona/workspace/metabolic-pptx && ls /home/daytona/workspace/me…

Writing File

~/metabolic-pptx/create_pptx.js

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// ═══════════════════════════════════════════════════════════════════
//  SLIDE 4 — GLUT TRANSPORTERS
// ═══════════════════════════════════════════════════════════════════
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  highYieldTag(s, 11.5, 0.12);

  const gluts = [
    { name: "GLUT-1", tissue: "Most tissues, RBCs, Brain barrier", feature: "Constitutive basal uptake", color: "023E8A" },
    { name: "GLUT-2", tissue: "Liver, Kidney, Pancreatic β-cells", feature: "High Km → glucose SENSOR; bidirectional", color: "1B4332" },
    { name: "GLUT-3", tissue: "Neurons (brain)", feature: "High affinity — ensures brain always gets glucose", color: "6A0572" },
    { name: "GLUT-4", tissue: "Skeletal muscle & Adipose", feature: "INSULIN-DEPENDENT ↑ insertion into membrane", color: "B5451B" },
    { name: "GLUT-5", tissue: "Small intestine, sperm", feature: "Transports FRUCTOSE (not glucose)", color: "7B2D00" },
  ];

  gluts.forEach((g, i) => {
    const x = 0.3 + (i % 3) * 4.3;
    const y = i < 3 ? 1.35 : 3.6;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y, w: 4.0, h: 2.0, fill: { color: g.color }, line: { color: C.teal, pt: 1.5 }, rectRadius: 0.12 });
    s.addText(g.name, { x: x + 0.15, y: y + 0.12, w: 3.7, h: 0.45, fontSize: 20, bold: true, color: C.yellow, margin: 0 });
    s.addText(g.tissue, { x: x + 0.15, y: y + 0.55, w: 3.7, h: 0.5, fontSize: 11.5, color: C.teal, margin: 0 });
    s.addShape(pres.shapes.RECTANGLE, { x: x + 0.15, y: y + 1.05, w: 3.65, h: 0.03, fill: { color: C.teal, transparency: 50 }, line: { type: "none" } });
    s.addText(g.feature, { x: x + 0.15, y: y + 1.1, w: 3.7, h: 0.7, fontSize: 11, color: C.white, italic: true, margin: 0 });
  });

  // MCQ tip
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 8.8, y: 3.6, w: 4.2, h: 2.0, fill: { color: "1A1A2E" }, line: { color: C.yellow, pt: 1.5 }, rectRadius: 0.12 });
  s.addText("MCQ TIP", { x: 8.9, y: 3.68, w: 4.0, h: 0.38, fontSize: 13, bold: true, color: C.yellow, margin: 0 });
  s.addText([
    { text: "• GLUT-4 = insulin-dependent\n", options: { color: C.white } },
    { text: "• GLUT-2 = glucose sensor in β-cells\n", options: { color: C.white } },
    { text: "• GLUT-5 = fructose (NOT glucose)\n", options: { color: C.white } },
    { text: "• No GLUT-4 in RBCs or neurons", options: { color: C.muted } },
  ], { x: 8.9, y: 4.1, w: 4.0, h: 1.4, fontSize: 11, margin: 0, lineSpacingMultiple: 1.3 });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 5 — TCA CYCLE
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.lightBg };
  headerBar(s, "TCA Cycle (Krebs / Citric Acid Cycle)", "Mitochondrial matrix • Main ATP generator");
  highYieldTag(s, 11.5, 0.12);

  // Steps table
  const rows = [
    [{ text: "Reaction", options: { bold: true, color: C.white, fill: { color: C.navy } } },
     { text: "Enzyme", options: { bold: true, color: C.white, fill: { color: C.navy } } },
     { text: "Cofactor / Note", options: { bold: true, color: C.white, fill: { color: C.navy } } }],
    ["Acetyl-CoA + OAA → Citrate", "Citrate synthase", "Inhibited by NADH, succinyl-CoA, ATP"],
    ["Citrate → Isocitrate", "Aconitase", "Fe-S cluster; fluoroacetate blocks"],
    ["Isocitrate → α-Ketoglutarate + CO₂", "Isocitrate DH ★ Rate-limiting", "NAD⁺ → NADH; activated by ADP, Ca²⁺"],
    ["α-KG → Succinyl-CoA + CO₂", "α-KG dehydrogenase", "TPP, lipoate, FAD, NAD⁺, CoA (same as PDH)"],
    ["Succinyl-CoA → Succinate", "Succinyl-CoA synthetase", "Substrate-level: GTP formed"],
    ["Succinate → Fumarate", "Succinate DH (Complex II)", "FADH₂; inhibited by malonate"],
    ["Fumarate → Malate", "Fumarase", "—"],
    ["Malate → OAA", "Malate dehydrogenase", "NAD⁺ → NADH; completes cycle"],
  ];

  const rowColors = ["", "F0F8FF", "FFFFFF", "F0F8FF", "FFFFFF", "F0F8FF", "FFFFFF", "F0F8FF", "FFFFFF"];
  const tableData = rows.map((row, ri) =>
    row.map((cell, ci) => {
      if (typeof cell === "object") return cell;
      const opts = { color: C.textDark, fontSize: 10.5 };
      if (ri > 0) opts.fill = { color: rowColors[ri] };
      if (ci === 1 && ri > 0) opts.bold = true;
      return { text: cell, options: opts };
    })
  );

  s.addTable(tableData, {
    x: 0.3, y: 1.3, w: 12.7, h: 5.5,
    colW: [3.6, 3.2, 5.9],
    border: { pt: 0.5, color: "CCCCCC" },
    rowH: 0.55,
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 6 — TCA YIELD + VITAMINS
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.navy };
  headerBar(s, "TCA Cycle — ATP Yield & Vitamins", "Per acetyl-CoA turn + Anaplerosis");

  // ATP yield cards
  const yields = [
    { label: "3 × NADH", atp: "7.5 ATP", note: "(2.5 each)", color: "023E8A" },
    { label: "1 × FADH₂", atp: "1.5 ATP", note: "(1.5 each)", color: "1B4332" },
    { label: "1 × GTP", atp: "1 ATP", note: "Substrate-level", color: "6A0572" },
    { label: "TOTAL", atp: "10 ATP", note: "Per acetyl-CoA", color: "B5451B" },
  ];
  yields.forEach((y, i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3 + i * 3.2, y: 1.3, w: 2.9, h: 1.6, fill: { color: y.color }, line: { type: "none" }, rectRadius: 0.1 });
    s.addText(y.label, { x: 0.3 + i * 3.2, y: 1.38, w: 2.9, h: 0.4, fontSize: 12, color: C.teal, bold: true, align: "center", margin: 0 });
    s.addText(y.atp, { x: 0.3 + i * 3.2, y: 1.78, w: 2.9, h: 0.55, fontSize: 24, color: C.yellow, bold: true, align: "center", margin: 0 });
    s.addText(y.note, { x: 0.3 + i * 3.2, y: 2.33, w: 2.9, h: 0.35, fontSize: 10, color: C.muted, align: "center", italic: true, margin: 0 });
  });

  // Per glucose
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 3.1, w: 12.7, h: 0.55, fill: { color: C.teal, transparency: 10 }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("Per GLUCOSE → 2 acetyl-CoA → 20 ATP from TCA alone  |  Total oxidation of glucose ≈ 30–32 ATP", {
    x: 0.3, y: 3.1, w: 12.7, h: 0.55, fontSize: 14, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0
  });

  // Vitamins
  s.addShape(pres.shapes.RECTANGLE, { x: 0.3, y: 3.85, w: 12.7, h: 0.38, fill: { color: C.cardBg }, line: { type: "none" } });
  s.addText("VITAMINS IN TCA CYCLE  — Mnemonic: T-L-N-F-B", { x: 0.3, y: 3.85, w: 12.7, h: 0.38, fontSize: 13, bold: true, color: C.yellow, align: "center", valign: "middle", margin: 0 });

  const vits = [
    { letter: "T", name: "Thiamine (B1)", use: "PDH, α-KG DH, Transketolase", color: "023E8A" },
    { letter: "L", name: "Lipoic Acid", use: "PDH, α-KG DH", color: "1B4332" },
    { letter: "N", name: "Niacin (B3/NAD⁺)", use: "Multiple dehydrogenases", color: "6A0572" },
    { letter: "F", name: "Flavin (B2/FAD)", use: "Succinate DH, PDH", color: "B5451B" },
    { letter: "B", name: "Biotin (B7)", use: "Pyruvate carboxylase (anaplerosis)", color: "7B2D00" },
  ];
  vits.forEach((v, i) => {
    const x = 0.3 + i * 2.55;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y: 4.35, w: 2.4, h: 2.7, fill: { color: v.color }, line: { type: "none" }, rectRadius: 0.1 });
    s.addText(v.letter, { x, y: 4.42, w: 2.4, h: 0.65, fontSize: 32, bold: true, color: C.yellow, align: "center", margin: 0 });
    s.addText(v.name, { x: x + 0.1, y: 5.05, w: 2.2, h: 0.45, fontSize: 11.5, color: C.white, bold: true, align: "center", margin: 0 });
    s.addText(v.use, { x: x + 0.1, y: 5.5, w: 2.2, h: 1.4, fontSize: 10, color: C.muted, align: "center", margin: 0, lineSpacingMultiple: 1.3 });
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 7 — PDH COMPLEX
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.lightBg };
  headerBar(s, "Pyruvate Dehydrogenase Complex (PDH)", "Bridge between glycolysis & TCA • Mitochondrial matrix • IRREVERSIBLE");
  highYieldTag(s, 11.5, 0.12);

  // Central reaction
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 2.0, y: 1.35, w: 9.3, h: 0.75, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.1 });
  s.addText("Pyruvate  →  Acetyl-CoA  +  CO₂  +  NADH", {
    x: 2.0, y: 1.35, w: 9.3, h: 0.75, fontSize: 20, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0
  });

  // Cofactors
  s.addText("COFACTORS (mnemonic: T-L-C-F-N)", { x: 0.3, y: 2.3, w: 6, h: 0.38, fontSize: 14, bold: true, color: C.navy, margin: 0 });
  const cofs = [
    { l: "T", n: "TPP", v: "Thiamine B1" },
    { l: "L", n: "Lipoic acid", v: "Lipoamide" },
    { l: "C", n: "CoA", v: "B5 Pantothenate" },
    { l: "F", n: "FAD", v: "Riboflavin B2" },
    { l: "N", n: "NAD⁺", v: "Niacin B3" },
  ];
  cofs.forEach((c, i) => {
    const y = 2.78 + i * 0.72;
    s.addShape(pres.shapes.OVAL, { x: 0.3, y: y + 0.05, w: 0.55, h: 0.55, fill: { color: C.teal }, line: { type: "none" } });
    s.addText(c.l, { x: 0.3, y: y + 0.05, w: 0.55, h: 0.55, fontSize: 16, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0 });
    s.addText(c.n + "  —  " + c.v, { x: 1.0, y, w: 5, h: 0.65, fontSize: 13, color: C.textDark, valign: "middle", margin: 0 });
  });

  // Regulation
  s.addShape(pres.shapes.RECTANGLE, { x: 6.5, y: 2.25, w: 6.5, h: 0.38, fill: { color: C.navy }, line: { type: "none" } });
  s.addText("REGULATION", { x: 6.5, y: 2.25, w: 6.5, h: 0.38, fontSize: 13, bold: true, color: C.yellow, align: "center", valign: "middle", margin: 0 });

  const activators = ["AMP", "CoA", "NAD⁺", "Ca²⁺", "Insulin (via PDH phosphatase)"];
  const inhibitors = ["ATP", "Acetyl-CoA", "NADH", "Fatty acids", "PDH kinase (phosphorylates → OFF)"];

  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.5, y: 2.73, w: 3.0, h: 4.0, fill: { color: "E8F8F5" }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("✔ ACTIVATORS", { x: 6.5, y: 2.8, w: 3.0, h: 0.38, fontSize: 12, bold: true, color: "1B4332", align: "center", margin: 0 });
  activators.forEach((a, i) => {
    s.addText("• " + a, { x: 6.7, y: 3.22 + i * 0.6, w: 2.7, h: 0.5, fontSize: 12, color: "1B4332", margin: 0 });
  });

  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 9.7, y: 2.73, w: 3.0, h: 4.0, fill: { color: "FFF0F0" }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("✘ INHIBITORS", { x: 9.7, y: 2.8, w: 3.0, h: 0.38, fontSize: 12, bold: true, color: C.red, align: "center", margin: 0 });
  inhibitors.forEach((a, i) => {
    s.addText("• " + a, { x: 9.9, y: 3.22 + i * 0.6, w: 2.7, h: 0.5, fontSize: 12, color: C.red, margin: 0 });
  });

  // Clinical pearl
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 6.5, w: 5.8, h: 0.72, fill: { color: C.yellow, transparency: 15 }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("★ CLINICAL: Thiamine (B1) deficiency → PDH block → pyruvate → lactate (lactic acidosis) → Wernicke's / Beriberi", {
    x: 0.4, y: 6.53, w: 5.6, h: 0.65, fontSize: 11, color: C.textDark, bold: true, margin: 0, lineSpacingMultiple: 1.2
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 8 — GLUCONEOGENESIS
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.lightBg };
  headerBar(s, "Gluconeogenesis", "New glucose synthesis from non-carbohydrate precursors");
  highYieldTag(s, 11.5, 0.12);

  // Precursors
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.3, w: 3.5, h: 0.4, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("SUBSTRATES", { x: 0.3, y: 1.3, w: 3.5, h: 0.4, fontSize: 12, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0 });
  const substrates = [
    ["Lactate", "Cori cycle: muscle → liver", "023E8A"],
    ["Glycerol", "From TAG hydrolysis in adipose", "1B4332"],
    ["Amino acids", "All glucogenic (ALL except Leu & Lys)", "6A0572"],
    ["Propionate", "Odd-chain fatty acid β-oxidation", "B5451B"],
  ];
  substrates.forEach(([k, v, col], i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.82 + i * 1.1, w: 3.5, h: 0.95, fill: { color: col }, line: { type: "none" }, rectRadius: 0.08 });
    s.addText(k, { x: 0.45, y: 1.87 + i * 1.1, w: 3.2, h: 0.38, fontSize: 13, bold: true, color: C.white, margin: 0 });
    s.addText(v, { x: 0.45, y: 2.22 + i * 1.1, w: 3.2, h: 0.38, fontSize: 10.5, color: C.muted, margin: 0 });
  });

  // Bypass enzymes
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 4.1, y: 1.3, w: 8.9, h: 0.4, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("4 UNIQUE BYPASS ENZYMES (overcome irreversible glycolytic steps)", {
    x: 4.1, y: 1.3, w: 8.9, h: 0.4, fontSize: 12, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0
  });

  const bypasses = [
    { num: "1", enzyme: "Pyruvate Carboxylase", rxn: "Pyruvate → OAA", note: "Biotin cofactor; mitochondria; activated by acetyl-CoA", color: "023E8A" },
    { num: "2", enzyme: "PEPCK", rxn: "OAA → PEP", note: "Cytosol; GTP required; rate-limiting of gluconeogenesis", color: "1B4332" },
    { num: "3", enzyme: "Fructose-1,6-bisphosphatase", rxn: "F-1,6-bisP → F-6-P", note: "Inhibited by AMP, F-2,6-bisP; reciprocal to PFK-1", color: "6A0572" },
    { num: "4", enzyme: "Glucose-6-phosphatase", rxn: "G-6-P → Glucose", note: "ER membrane; liver & kidney only (NOT muscle/brain)", color: "B5451B" },
  ];
  bypasses.forEach((b, i) => {
    const y = 1.82 + i * 1.1;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 4.1, y, w: 8.9, h: 0.95, fill: { color: b.color }, line: { type: "none" }, rectRadius: 0.08 });
    s.addShape(pres.shapes.OVAL, { x: 4.15, y: y + 0.23, w: 0.45, h: 0.45, fill: { color: C.white, transparency: 20 }, line: { type: "none" } });
    s.addText(b.num, { x: 4.15, y: y + 0.23, w: 0.45, h: 0.45, fontSize: 14, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
    s.addText(b.enzyme, { x: 4.7, y: y + 0.07, w: 5.5, h: 0.38, fontSize: 13, bold: true, color: C.white, margin: 0 });
    s.addText(b.rxn, { x: 4.7, y: y + 0.44, w: 3.5, h: 0.32, fontSize: 11, color: C.teal, margin: 0 });
    s.addText(b.note, { x: 4.7, y: y + 0.55, w: 8.0, h: 0.35, fontSize: 10, color: C.muted, italic: true, margin: 0 });
  });

  // Cori cycle note
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 6.38, w: 12.7, h: 0.72, fill: { color: C.yellow, transparency: 10 }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("★ CORI CYCLE: Muscle (Glucose → Lactate) ↔ Liver (Lactate → Glucose)  |  Cost: 4 net ATP to liver  |  Leucine & Lysine = purely KETOGENIC (cannot make glucose)", {
    x: 0.4, y: 6.42, w: 12.5, h: 0.65, fontSize: 11, bold: true, color: C.textDark, margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 9 — GLYCOGEN METABOLISM
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.navy };
  headerBar(s, "Glycogen Metabolism", "Synthesis & Breakdown • Liver (blood glucose) vs Muscle (fuel)");
  highYieldTag(s, 11.5, 0.12);

  // Synthesis side
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.3, w: 6.1, h: 0.42, fill: { color: "023E8A" }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("GLYCOGEN SYNTHESIS", { x: 0.3, y: 1.3, w: 6.1, h: 0.42, fontSize: 13, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
  const syn = [
    "G-6-P → G-1-P  (Phosphoglucomutase)",
    "G-1-P + UTP → UDP-Glucose  (UDP-Glucose pyrophosphorylase)",
    "UDP-Glucose + glycogen → extended chain  (Glycogen synthase ★)",
    "Branching enzyme creates α-1,6 branches every 8–10 residues",
  ];
  syn.forEach((t, i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.82 + i * 0.85, w: 6.1, h: 0.72, fill: { color: C.cardBg }, line: { type: "none" }, rectRadius: 0.06 });
    s.addText((i + 1) + ".  " + t, { x: 0.45, y: 1.85 + i * 0.85, w: 5.8, h: 0.68, fontSize: 11, color: C.white, valign: "middle", margin: 0 });
  });

  // Breakdown side
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.8, y: 1.3, w: 6.2, h: 0.42, fill: { color: "B5451B" }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("GLYCOGEN BREAKDOWN", { x: 6.8, y: 1.3, w: 6.2, h: 0.42, fontSize: 13, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
  const brk = [
    "Glycogen phosphorylase cleaves α-1,4 bonds → G-1-P",
    "Debranching enzyme handles α-1,6 branches → free glucose",
    "G-1-P → G-6-P → Glucose (liver via G-6-Pase); Muscle uses G-6-P for glycolysis",
  ];
  brk.forEach((t, i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.8, y: 1.82 + i * 0.85, w: 6.2, h: 0.72, fill: { color: C.cardBg }, line: { type: "none" }, rectRadius: 0.06 });
    s.addText((i + 1) + ".  " + t, { x: 6.95, y: 1.85 + i * 0.85, w: 6.0, h: 0.68, fontSize: 11, color: C.white, valign: "middle", margin: 0 });
  });

  // GSD table header
  s.addShape(pres.shapes.RECTANGLE, { x: 0.3, y: 4.62, w: 12.7, h: 0.38, fill: { color: C.teal }, line: { type: "none" } });
  s.addText("GLYCOGEN STORAGE DISEASES (GSDs) — Frequently Tested!", {
    x: 0.3, y: 4.62, w: 12.7, h: 0.38, fontSize: 13, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0
  });

  const gsds = [
    ["Type I — Von Gierke", "Glucose-6-phosphatase", "Liver, Kidney", "Hypoglycemia, ↑ lactate, hepatomegaly"],
    ["Type II — Pompe", "Acid maltase (lysosomal)", "Heart, Muscle", "Cardiomegaly, hypotonia; ONLY lysosomal GSD"],
    ["Type III — Cori", "Debranching enzyme", "Liver, Muscle", "Milder Von Gierke-like features"],
    ["Type V — McArdle", "Muscle phosphorylase", "Muscle only", "No lactate ↑ in ischemic exercise test"],
  ];
  const gsdRows = [
    [{ text: "Disease", options: { bold: true, color: C.white, fill: { color: C.navy } } },
     { text: "Enzyme Deficient", options: { bold: true, color: C.white, fill: { color: C.navy } } },
     { text: "Organ", options: { bold: true, color: C.white, fill: { color: C.navy } } },
     { text: "Key Feature", options: { bold: true, color: C.white, fill: { color: C.navy } } }],
    ...gsds.map((row, i) => row.map(cell => ({ text: cell, options: { color: C.textDark, fill: { color: i % 2 === 0 ? "E8F4FD" : C.white }, fontSize: 10.5 } })))
  ];
  s.addTable(gsdRows, { x: 0.3, y: 5.08, w: 12.7, h: 2.1, colW: [3.2, 3.2, 2.2, 4.1], border: { pt: 0.5, color: "CCCCCC" }, rowH: 0.48 });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 10 — HMP SHUNT
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.lightBg };
  headerBar(s, "HMP Shunt (Pentose Phosphate Pathway)", "Cytosol • Produces NADPH + Ribose-5-P • No ATP directly");
  highYieldTag(s, 11.5, 0.12);

  // Phase cards
  const phases = [
    {
      title: "OXIDATIVE PHASE (Irreversible)",
      color: "023E8A",
      items: [
        "G-6-P → 6-Phosphogluconolactone  (G6PD ★ rate-limiting)",
        "6-Phosphogluconate → Ribulose-5-P + CO₂",
        "Generates 2 NADPH per glucose",
      ]
    },
    {
      title: "NON-OXIDATIVE PHASE (Reversible)",
      color: "1B4332",
      items: [
        "Interconverts sugar phosphates (C3–C7)",
        "Transketolase — needs Thiamine (TPP)",
        "Transaldolase — no cofactor",
      ]
    }
  ];
  phases.forEach((p, i) => {
    const x = 0.3 + i * 6.5;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y: 1.3, w: 6.2, h: 0.42, fill: { color: p.color }, line: { type: "none" }, rectRadius: 0.07 });
    s.addText(p.title, { x, y: 1.3, w: 6.2, h: 0.42, fontSize: 12, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
    p.items.forEach((it, j) => {
      s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y: 1.82 + j * 0.78, w: 6.2, h: 0.66, fill: { color: j % 2 === 0 ? C.cardBg : "1A2035" }, line: { type: "none" }, rectRadius: 0.06 });
      s.addText("• " + it, { x: x + 0.15, y: 1.85 + j * 0.78, w: 5.9, h: 0.62, fontSize: 12, color: C.white, valign: "middle", margin: 0 });
    });
  });

  // NADPH functions
  s.addShape(pres.shapes.RECTANGLE, { x: 0.3, y: 4.22, w: 12.7, h: 0.4, fill: { color: C.navy }, line: { type: "none" } });
  s.addText("FUNCTIONS OF NADPH", { x: 0.3, y: 4.22, w: 12.7, h: 0.4, fontSize: 13, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0 });

  const fns = [
    ["Antioxidant", "Regenerates reduced glutathione → protects RBCs from oxidative damage"],
    ["Fatty acid synthesis", "Required by fatty acid synthase"],
    ["Cholesterol synthesis", "HMG-CoA reductase pathway"],
    ["Cytochrome P450", "Drug metabolism in liver"],
    ["Respiratory burst", "NADPH oxidase in neutrophils → superoxide → kills bacteria"],
  ];
  fns.forEach(([k, v], i) => {
    const x = 0.3 + (i % 3) * 4.3;
    const y = i < 3 ? 4.75 : 5.95;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y, w: 4.0, h: 1.0, fill: { color: C.cardBg }, line: { color: C.teal, pt: 1 }, rectRadius: 0.08 });
    s.addText(k, { x: x + 0.12, y: y + 0.06, w: 3.76, h: 0.38, fontSize: 12, bold: true, color: C.teal, margin: 0 });
    s.addText(v, { x: x + 0.12, y: y + 0.42, w: 3.76, h: 0.52, fontSize: 10, color: C.white, margin: 0 });
  });

  // G6PD deficiency box
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 8.9, y: 4.75, w: 4.1, h: 2.2, fill: { color: C.red, transparency: 10 }, line: { type: "none" }, rectRadius: 0.1 });
  s.addText("G6PD DEFICIENCY", { x: 8.9, y: 4.83, w: 4.1, h: 0.4, fontSize: 13, bold: true, color: C.white, align: "center", margin: 0 });
  s.addText([
    { text: "• X-linked; most common enzyme deficiency\n", options: { color: C.white } },
    { text: "• Triggers: Primaquine, dapsone, sulfa drugs, fava beans\n", options: { color: C.white } },
    { text: "• Result: Hemolysis — Heinz bodies + bite cells\n", options: { color: C.white } },
    { text: "• Mechanism: ↓ NADPH → ↓ GSH → RBC oxidative damage", options: { color: C.muted } },
  ], { x: 9.05, y: 5.28, w: 3.85, h: 1.6, fontSize: 10.5, margin: 0, lineSpacingMultiple: 1.35 });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 11 — FATTY ACID METABOLISM
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.navy };
  headerBar(s, "Fatty Acid Metabolism", "β-Oxidation • Ketogenesis • Fatty Acid Synthesis");
  highYieldTag(s, 11.5, 0.12);

  // Beta-oxidation
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.3, w: 6.1, h: 0.4, fill: { color: "023E8A" }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("β-OXIDATION (Mitochondrial matrix)", { x: 0.3, y: 1.3, w: 6.1, h: 0.4, fontSize: 13, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });

  const betaItems = [
    ["Activation", "FA + CoA → Acyl-CoA (outer mitochondrial membrane; costs 2 ATP equivalents)"],
    ["Transport", "CPT-I ★ Rate-limiting — carnitine shuttle; inhibited by malonyl-CoA"],
    ["Per cycle", "Acyl-CoA → (shorter by 2C) + Acetyl-CoA + FADH₂ + NADH"],
    ["Palmitate (C16)", "7 cycles → 8 acetyl-CoA + 7 FADH₂ + 7 NADH → ~106 net ATP"],
    ["Odd-chain FA", "→ Propionyl-CoA → Succinyl-CoA (gluconeogenic via B12 pathway)"],
  ];
  betaItems.forEach(([k, v], i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.82 + i * 0.78, w: 6.1, h: 0.68, fill: { color: C.cardBg }, line: { type: "none" }, rectRadius: 0.06 });
    s.addText(k + ": ", { x: 0.45, y: 1.87 + i * 0.78, w: 1.5, h: 0.6, fontSize: 11, bold: true, color: C.teal, valign: "middle", margin: 0 });
    s.addText(v, { x: 1.75, y: 1.87 + i * 0.78, w: 4.5, h: 0.6, fontSize: 10.5, color: C.white, valign: "middle", margin: 0 });
  });

  // Ketogenesis
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.7, y: 1.3, w: 6.3, h: 0.4, fill: { color: "B5451B" }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("KETOGENESIS — Liver mitochondria only", { x: 6.7, y: 1.3, w: 6.3, h: 0.4, fontSize: 13, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });

  const ketoItems = [
    "Occurs in: Fasting, starvation, uncontrolled T1DM",
    "2 Acetyl-CoA → Acetoacetyl-CoA → HMG-CoA → Acetoacetate",
    "Rate-limiting enzyme: HMG-CoA synthase (mitochondrial)",
    "Products: Acetoacetate, β-hydroxybutyrate, acetone",
    "Liver CANNOT use ketones (lacks succinyl-CoA transferase)",
    "Brain uses ketones after 2–3 days of fasting (spares glucose)",
    "Used by: Heart, muscle, brain (starvation), kidney cortex",
  ];
  ketoItems.forEach((it, i) => {
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.7, y: 1.82 + i * 0.65, w: 6.3, h: 0.56, fill: { color: i % 2 === 0 ? C.cardBg : "1A1020" }, line: { type: "none" }, rectRadius: 0.05 });
    s.addText("• " + it, { x: 6.85, y: 1.85 + i * 0.65, w: 6.1, h: 0.52, fontSize: 10.5, color: C.white, valign: "middle", margin: 0 });
  });

  // Malonyl-CoA key note
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 6.4, w: 12.7, h: 0.72, fill: { color: C.yellow, transparency: 10 }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("★ MALONYL-CoA (first committed step of FA synthesis by ACC) inhibits CPT-I → prevents FA transport into mitochondria → prevents β-oxidation when synthesizing FA", {
    x: 0.4, y: 6.43, w: 12.5, h: 0.65, fontSize: 11, bold: true, color: C.textDark, margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 12 — UREA CYCLE + ETC
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.lightBg };
  headerBar(s, "Urea Cycle & Electron Transport Chain", "Nitrogen disposal + ATP generation");

  // Urea Cycle
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.3, w: 6.0, h: 0.42, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("UREA CYCLE  (Liver: mitochondria + cytosol)", { x: 0.3, y: 1.3, w: 6.0, h: 0.42, fontSize: 13, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0 });

  const ureaCycle = [
    { step: "1", rxn: "NH₃ + CO₂ → Carbamoyl-P", note: "CPS-I; mitochondria; N-acetylglutamate (NAG) activator", color: "023E8A" },
    { step: "2", rxn: "Carbamoyl-P + Ornithine → Citrulline", note: "Ornithine transcarbamoylase; exits to cytosol", color: "1B4332" },
    { step: "3", rxn: "Citrulline + Aspartate → Argininosuccinate", note: "Argininosuccinate synthetase; ATP used", color: "6A0572" },
    { step: "4", rxn: "Argininosuccinate → Arginine + Fumarate", note: "Fumarate enters TCA cycle (anaplerosis)", color: "B5451B" },
    { step: "5", rxn: "Arginine → Ornithine + Urea", note: "Arginase; ornithine recycled back into mitochondria", color: "7B2D00" },
  ];
  ureaCycle.forEach((u, i) => {
    const y = 1.82 + i * 0.88;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y, w: 6.0, h: 0.78, fill: { color: u.color }, line: { type: "none" }, rectRadius: 0.08 });
    s.addShape(pres.shapes.OVAL, { x: 0.35, y: y + 0.17, w: 0.4, h: 0.4, fill: { color: C.white, transparency: 20 }, line: { type: "none" } });
    s.addText(u.step, { x: 0.35, y: y + 0.17, w: 0.4, h: 0.4, fontSize: 12, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
    s.addText(u.rxn, { x: 0.88, y: y + 0.05, w: 5.3, h: 0.36, fontSize: 11.5, bold: true, color: C.white, margin: 0 });
    s.addText(u.note, { x: 0.88, y: y + 0.4, w: 5.3, h: 0.3, fontSize: 9.5, color: C.muted, italic: true, margin: 0 });
  });

  // ETC
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.6, y: 1.3, w: 6.4, h: 0.42, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("ELECTRON TRANSPORT CHAIN (ETC)", { x: 6.6, y: 1.3, w: 6.4, h: 0.42, fontSize: 13, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0 });

  const etc = [
    { cx: "I", name: "NADH Dehydrogenase", carrier: "NADH → CoQ", inh: "Rotenone, Amobarbital", color: "023E8A" },
    { cx: "II", name: "Succinate DH", carrier: "FADH₂ → CoQ", inh: "Malonate", color: "1B4332" },
    { cx: "III", name: "CoQ-Cyt c reductase", carrier: "CoQ → Cyt c", inh: "Antimycin A", color: "6A0572" },
    { cx: "IV", name: "Cytochrome c oxidase", carrier: "Cyt c → O₂", inh: "Cyanide, CO, Azide ★", color: "B5451B" },
    { cx: "V", name: "ATP Synthase", carrier: "H⁺ gradient → ATP", inh: "Oligomycin", color: "7B2D00" },
  ];
  etc.forEach((e, i) => {
    const y = 1.82 + i * 0.88;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.6, y, w: 6.4, h: 0.78, fill: { color: e.color }, line: { type: "none" }, rectRadius: 0.08 });
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.65, y: y + 0.16, w: 0.55, h: 0.42, fill: { color: C.white, transparency: 20 }, line: { type: "none" }, rectRadius: 0.05 });
    s.addText("CX " + e.cx, { x: 6.65, y: y + 0.16, w: 0.55, h: 0.42, fontSize: 8, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
    s.addText(e.name, { x: 7.3, y: y + 0.05, w: 4.0, h: 0.36, fontSize: 11.5, bold: true, color: C.white, margin: 0 });
    s.addText(e.carrier, { x: 7.3, y: y + 0.4, w: 2.5, h: 0.28, fontSize: 10, color: C.teal, margin: 0 });
    s.addText("Inhibitor: " + e.inh, { x: 10.0, y: y + 0.38, w: 2.9, h: 0.32, fontSize: 10, color: C.red, italic: true, margin: 0 });
  });

  // Uncoupler note
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 6.38, w: 12.7, h: 0.75, fill: { color: C.yellow, transparency: 10 }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("★ UNCOUPLERS: Dissipate H⁺ gradient without ATP synthesis → heat. Examples: DNP (2,4-dinitrophenol), Thermogenin/UCP-1 (brown fat), Aspirin OD  |  NAG activates CPS-I → essential for urea cycle start", {
    x: 0.4, y: 6.42, w: 12.5, h: 0.65, fontSize: 11, bold: true, color: C.textDark, margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 13 — MASTER TABLE: RATE-LIMITING ENZYMES
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.navy };
  headerBar(s, "Rate-Limiting Enzymes — Master Summary", "Most commonly tested in NEET PG MCQs");
  highYieldTag(s, 11.5, 0.12);

  const rle = [
    ["Glycolysis", "PFK-1 (Phosphofructokinase-1)", "↑ AMP, F-2,6-bisP  |  ↓ ATP, citrate", "023E8A"],
    ["TCA Cycle", "Isocitrate dehydrogenase", "↑ ADP, Ca²⁺  |  ↓ ATP, NADH", "1B4332"],
    ["Gluconeogenesis", "PEPCK (rate-limiting step)", "↑ glucagon  |  ↓ insulin", "6A0572"],
    ["Glycogen synthesis", "Glycogen synthase", "↑ insulin, G-6-P  |  ↓ glucagon, PKA", "7B2D00"],
    ["Glycogenolysis", "Glycogen phosphorylase", "↑ glucagon, epi, AMP  |  ↓ insulin", "B5451B"],
    ["FA synthesis", "Acetyl-CoA carboxylase (ACC)", "↑ insulin, citrate  |  ↓ glucagon, fatty acids", "023E8A"],
    ["β-Oxidation", "CPT-I (carnitine shuttle)", "Inhibited by malonyl-CoA (FA synthesis active)", "1B4332"],
    ["Ketogenesis", "HMG-CoA synthase (mitochondrial)", "↑ fasting, T1DM  |  ↓ insulin", "6A0572"],
    ["HMP Shunt", "G6PD (Glucose-6-P DH)", "↑ NADP⁺  |  X-linked; deficiency = hemolysis", "7B2D00"],
    ["Cholesterol synthesis", "HMG-CoA reductase", "↑ insulin  |  ↓ glucagon, statins, cholesterol", "B5451B"],
    ["Urea cycle", "CPS-I (Carbamoyl phosphate synthetase I)", "↑ N-acetylglutamate (NAG)", "023E8A"],
    ["Pyrimidine synthesis", "Carbamoyl phosphate synthetase II", "Cytosol (diff from CPS-I which is mitochondrial)", "1B4332"],
  ];

  const tableRows = [
    [
      { text: "Pathway", options: { bold: true, color: C.white, fill: { color: C.teal, transparency: 10 } } },
      { text: "Rate-Limiting Enzyme", options: { bold: true, color: C.white, fill: { color: C.teal, transparency: 10 } } },
      { text: "Regulation", options: { bold: true, color: C.white, fill: { color: C.teal, transparency: 10 } } },
    ],
    ...rle.map((row, i) => row.slice(0, 3).map((cell, ci) => ({
      text: cell,
      options: {
        color: ci === 1 ? C.teal : C.white,
        bold: ci === 1,
        fill: { color: i % 2 === 0 ? C.cardBg : "0F1E30" },
        fontSize: 10.5
      }
    })))
  ];

  s.addTable(tableRows, {
    x: 0.3, y: 1.3, w: 12.7, h: 5.9,
    colW: [2.6, 4.5, 5.6],
    border: { pt: 0.5, color: "334455" },
    rowH: 0.44,
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 14 — HORMONAL REGULATION
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.lightBg };
  headerBar(s, "Hormonal Regulation of Metabolism", "Insulin vs Glucagon — The master switch");
  highYieldTag(s, 11.5, 0.12);

  const insulin = [
    "↑ Glycolysis (↑ PFK-1, ↑ PK)",
    "↑ Glycogen synthesis (↑ Glycogen synthase)",
    "↑ Fatty acid synthesis (↑ ACC, ↑ FA synthase)",
    "↑ Protein synthesis",
    "↓ Gluconeogenesis (↓ PEPCK)",
    "↓ Glycogenolysis",
    "↓ Ketogenesis",
    "↑ GLUT-4 insertion (muscle, adipose)",
  ];
  const glucagon = [
    "↑ Gluconeogenesis (↑ PEPCK)",
    "↑ Glycogenolysis (↑ Glycogen phosphorylase)",
    "↑ Ketogenesis (↑ HMG-CoA synthase)",
    "↑ Fatty acid mobilization",
    "↓ Glycolysis (↓ PFK-1, ↓ PK via phosphorylation)",
    "↓ Glycogen synthesis",
    "↓ Fatty acid synthesis (↓ ACC)",
    "Acts via cAMP → PKA cascade",
  ];

  // Insulin panel
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.35, w: 6.1, h: 0.5, fill: { color: "023E8A" }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("INSULIN  (Fed state / post-meal)", { x: 0.3, y: 1.35, w: 6.1, h: 0.5, fontSize: 15, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
  insulin.forEach((item, i) => {
    const isUp = item.startsWith("↑");
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 1.98 + i * 0.6, w: 6.1, h: 0.52, fill: { color: i % 2 === 0 ? "E8F4FD" : C.white }, line: { type: "none" }, rectRadius: 0.05 });
    s.addText(item, { x: 0.45, y: 2.01 + i * 0.6, w: 5.8, h: 0.48, fontSize: 12, color: isUp ? "023E8A" : C.red, bold: isUp, valign: "middle", margin: 0 });
  });

  // Glucagon panel
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.9, y: 1.35, w: 6.1, h: 0.5, fill: { color: "B5451B" }, line: { type: "none" }, rectRadius: 0.08 });
  s.addText("GLUCAGON  (Fasting / starvation)", { x: 6.9, y: 1.35, w: 6.1, h: 0.5, fontSize: 15, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
  glucagon.forEach((item, i) => {
    const isUp = item.startsWith("↑");
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.9, y: 1.98 + i * 0.6, w: 6.1, h: 0.52, fill: { color: i % 2 === 0 ? "FFF0E8" : C.white }, line: { type: "none" }, rectRadius: 0.05 });
    s.addText(item, { x: 7.05, y: 2.01 + i * 0.6, w: 5.8, h: 0.48, fontSize: 12, color: isUp ? "B5451B" : "023E8A", bold: isUp, valign: "middle", margin: 0 });
  });

  // F-2,6-bisP note
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.3, y: 6.85, w: 6.1, h: 0.5, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("F-2,6-bisP: ↑ PFK-1 (glycolysis) AND ↓ FBPase-1 (gluconeogenesis)", {
    x: 0.3, y: 6.85, w: 6.1, h: 0.5, fontSize: 11, bold: true, color: C.teal, align: "center", valign: "middle", margin: 0
  });
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 6.9, y: 6.85, w: 6.1, h: 0.5, fill: { color: C.navy }, line: { type: "none" }, rectRadius: 0.06 });
  s.addText("Glucagon → ↑ cAMP → ↑ PKA → phosphorylation inactivates glycolytic enzymes", {
    x: 6.9, y: 6.85, w: 6.1, h: 0.5, fontSize: 11, bold: true, color: C.orange, align: "center", valign: "middle", margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════
//  SLIDE 15 — NEET PG MUST-KNOW FACTS
// ═══════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: C.navy };
  headerBar(s, "NEET PG Must-Know Facts & MCQ Tips", "Quick revision before exam");
  highYieldTag(s, 11.5, 0.12);

  const facts = [
    { num: "1", fact: "PDH reaction is IRREVERSIBLE → fat cannot make glucose (Acetyl-CoA cannot enter gluconeogenesis)", color: "023E8A" },
    { num: "2", fact: "Only purely KETOGENIC AAs = Leucine & Lysine ('LL' — no glucose from these)", color: "1B4332" },
    { num: "3", fact: "Muscle has NO Glucose-6-phosphatase → muscle glycogen CANNOT contribute to blood glucose", color: "6A0572" },
    { num: "4", fact: "Hexokinase (tissues) vs Glucokinase (liver/β-cells): GK not inhibited by G-6-P, induced by insulin", color: "B5451B" },
    { num: "5", fact: "Pompe disease (Type II GSD) = ONLY lysosomal GSD; cardiomegaly; acid maltase deficiency", color: "7B2D00" },
    { num: "6", fact: "McArdle disease (Type V GSD) = muscle phosphorylase; NO lactate rise with ischemic exercise test", color: "023E8A" },
    { num: "7", fact: "Cyanide/CO → inhibit Complex IV → histotoxic hypoxia (cells cannot use O₂)", color: "B5451B" },
    { num: "8", fact: "Thiamine B1 deficiency → blocks PDH + α-KG DH + Transketolase → lactic acidosis, Wernicke's", color: "1B4332" },
    { num: "9", fact: "G6PD deficiency triggers: Primaquine, dapsone, sulfonamides, fava beans, infections", color: "6A0572" },
    { num: "10", fact: "Malonyl-CoA (FA synthesis) inhibits CPT-I → prevents futile FA synthesis + oxidation cycle", color: "7B2D00" },
  ];

  facts.forEach((f, i) => {
    const col = i < 5 ? 0 : 1;
    const row = i % 5;
    const x = 0.3 + col * 6.5;
    const y = 1.35 + row * 1.12;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y, w: 6.2, h: 1.0, fill: { color: f.color }, line: { type: "none" }, rectRadius: 0.1 });
    s.addShape(pres.shapes.OVAL, { x: x + 0.1, y: y + 0.25, w: 0.48, h: 0.48, fill: { color: C.yellow }, line: { type: "none" } });
    s.addText(f.num, { x: x + 0.1, y: y + 0.25, w: 0.48, h: 0.48, fontSize: 14, bold: true, color: C.textDark, align: "center", valign: "middle", margin: 0 });
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// ═══════════════════════════════════════════════════════════════════
//  SLIDE 16 — END / THANK YOU
// ═══════════════════════════════════════════════════════════════════
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  s.addText("Metabolic Pathways — NEET PG Quick Revision", { x: 1.75, y: 2.95, w: 10, h: 0.55, fontSize: 18, color: C.teal, italic: true, margin: 0 });
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  s.addText("Slides covered: Glycolysis • TCA Cycle • PDH • Gluconeogenesis • Glycogen\nHMP Shunt • Fatty Acids • Ketogenesis • Urea Cycle • ETC", {
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// ─── WRITE FILE ────────────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/metabolic-pptx/Metabolic_Pathways_NEET_PG.pptx" })
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  .catch(err => { console.error("ERROR:", err); process.exit(1); });

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