📚 MBBS Biochemistry: Questions 44-51 - Complete Exam-Oriented Guide

Q44. Cholesterol Biosynthesis, Regulation + Hypercholesterolemia & Hypocholesterolemia

🔷 FLOWCHART: Cholesterol Biosynthesis

ACETYL CoA (2 units)
        ↓  [Thiolase]
ACETOACETYL CoA
        ↓  [HMG CoA Synthase - cytosolic]
HMG CoA (3-Hydroxy-3-methylglutaryl CoA)
        ↓  [HMG CoA REDUCTASE] ← ★ RATE-LIMITING STEP
        ↓  (2 NADPH consumed, irreversible)
MEVALONATE (6C)
        ↓  [Mevalonate kinase → ATP]
MEVALONATE-5-PHOSPHATE
        ↓  [Phosphomevalonate kinase → ATP]
MEVALONATE-5-PYROPHOSPHATE
        ↓  [Decarboxylase → CO₂, ATP]
ISOPENTENYL PYROPHOSPHATE (IPP, 5C)
        ↓
GERANYL-PP (10C)
        ↓  [+ another IPP]
FARNESYL-PP (15C)
        ↓  [2 × Farnesyl-PP + NADPH → Squalene synthase]
SQUALENE (30C, linear)
        ↓  [Squalene monooxygenase + O₂]
SQUALENE EPOXIDE
        ↓  [Cyclization - Lanosterol synthase]
LANOSTEROL (first sterol, 30C)
        ↓  [19 enzyme steps, loss of 3C → CO₂]
CHOLESTEROL (27C)

• Site: Cytosol + SER (smooth ER) + peroxisome
• All carbons from Acetyl CoA
• Reducing power: NADPH
• HMG CoA reductase = integral SER membrane protein, catalytic domain faces cytosol

🔷 REGULATION OF CHOLESTEROL SYNTHESIS

                    HIGH INTRACELLULAR CHOLESTEROL
                              │
             ┌────────────────┴──────────────────┐
             ▼                                   ▼
    Inhibits HMG CoA Reductase          Activates ACAT
    (transcription ↓ + degradation ↑)   (esterifies cholesterol
                                          for storage)
             ▼
    Blocks SREBP-2 activation
    (SCAP-INSIG retain SREBP in ER)
             ▼
    No LDLR gene transcription
    (LDL receptors ↓ on cell surface)

                    LOW INTRACELLULAR CHOLESTEROL
                              │
             ┌────────────────┴──────────────────┐
             ▼                                   ▼
    INSIG releases SCAP-SREBP-2           HMG CoA Reductase
             ↓                              phosphorylation ↓
    SREBP-2 enters nucleus                 (inactive form ↓)
             ↓
    LDL Receptor gene + HMG CoA           
    Reductase gene → transcribed ↑

Hormonal Regulation:

Drug: STATINS (Lovastatin, Atorvastatin)

Competitive inhibitors of HMG CoA Reductase → ↓ cholesterol synthesis → ↑ LDL-R expression → ↓ plasma LDL

🔷 HYPERCHOLESTEROLEMIA

CAUSES:
┌─────────────────────────────────────┐
│ PRIMARY (Genetic)                   │
│  • Familial Hypercholesterolemia    │
│    - LDL-R mutation                 │
│    - Defective ApoB-100             │
│    - PCSK9 gain-of-function         │
│  • Familial Combined Hyperlipidemia │
│                                     │
│ SECONDARY (Acquired)                │
│  • Hypothyroidism                   │
│  • Nephrotic syndrome               │
│  • Diabetes mellitus                │
│  • Obesity                          │
│  • Obstructive jaundice             │
└─────────────────────────────────────┘
          ↓
CONSEQUENCES:
  • Atherosclerosis → CAD, stroke
  • Xanthomas (tendon, skin)
  • Xanthelasma (periorbital)
  • Arcus corneae (< 45 yr = pathological)

TREATMENT:
  Statins → Bile acid sequestrants → 
  Ezetimibe → PCSK9 inhibitors

🔷 HYPOCHOLESTEROLEMIA

CAUSES:
  • Abetalipoproteinemia (no ApoB → no VLDL/chylomicrons)
  • Hyperthyroidism
  • Malabsorption
  • Liver disease (cirrhosis)
  • Tangier disease (↓ HDL)

CONSEQUENCES:
  • Fat-soluble vitamin deficiency (A, D, E, K)
  • Acanthocytosis (spiny RBCs)
  • Neurological defects
  • Retinitis pigmentosa

Q45. Degradation of Cholesterol + Cholelithiasis

🔷 FLOWCHART: Cholesterol Degradation

CHOLESTEROL (27C)
      │
      ├──→ BILE ACIDS (major route of elimination)
      │         ↓
      │    Rate-limiting enzyme: 7-α-Hydroxylase (CYP7A1)
      │    [SER of liver, CYP enzyme]
      │    Regulated: ↑ by Cholesterol (via LXR)
      │               ↓ by Bile acids (via FXR/BAR)
      │         ↓
      │    PRIMARY BILE ACIDS:
      │    • Cholic acid (3-OH groups)
      │    • Chenodeoxycholic acid (2-OH groups)
      │         ↓
      │    Conjugated with Glycine or Taurine
      │    (Ratio Glycine:Taurine = 3:1)
      │         ↓
      │    Glycocholate, Taurocholate, etc.
      │         ↓
      │    Secreted into bile
      │         ↓
      │    In intestine → Bacterial deconjugation
      │         ↓
      │    SECONDARY BILE ACIDS:
      │    • Deoxycholic acid (from cholic)
      │    • Lithocholic acid (from chenodeoxycholic)
      │         ↓
      │    Enterohepatic circulation (95% reabsorbed)
      │    Only 5% excreted in feces
      │
      ├──→ STEROID HORMONES
      │    (Glucocorticoids, Mineralocorticoids,
      │     Sex hormones, Vitamin D)
      │
      └──→ Excreted unchanged in bile

🔷 CHOLELITHIASIS (Gallstones) - Exam High Yield

TYPES OF GALLSTONES:
┌──────────────────┬────────────────┬─────────────────┐
│ CHOLESTEROL      │ PIGMENT        │ MIXED           │
│ STONES (80%)     │ STONES (20%)   │                 │
├──────────────────┼────────────────┼─────────────────┤
│ • Pale yellow    │ • Black/Brown  │ Most common in  │
│ • Single, large  │ • Multiple     │ Western world   │
│ • Radiolucent    │ • Radioopaque  │                 │
│ • High chol in   │ • Bilirubin    │                 │
│   bile           │   calcium salts│                 │
└──────────────────┴────────────────┴─────────────────┘

MECHANISM (Cholesterol stones):
          ↓ Bile salts   OR   ↑ Cholesterol
                   ↓
         BILE SUPERSATURATED WITH CHOLESTEROL
                   ↓
         Cholesterol crystals nucleate
                   ↓
         Stone formation

RISK FACTORS ("5 F's"):
  Fat • Female • Forty • Fertile • Fair

COMPLICATIONS:
  Biliary colic → Acute cholecystitis → 
  Choledocholithiasis → Cholangitis → Pancreatitis

Q46. Metabolic Derangements in Obesity & Metabolic Syndrome

🔷 DIAGRAM: Metabolic Derangements in Obesity

EXCESS ENERGY INTAKE → OBESITY (BMI > 30)
              │
   ┌──────────┼──────────┬──────────────┐
   ▼          ▼          ▼              ▼
↑ Free FA  ↑ Adipokines  ↑ Visceral    ↑ Leptin
in blood   (↓ Adiponectin  fat         resistance
   │       ↑ TNF-α,IL-6)    │              │
   ▼          │             ▼              ▼
↑ Fatty acid  ▼         ↑ Portal FFA   Appetite
deposition  Inflammation  to liver     dysregulation
in liver/    (systemic)       │
muscle           │            ▼
   │             ▼      FATTY LIVER (NAFLD/NASH)
   ▼        INSULIN
↑ TG,       RESISTANCE
↓ HDL           │
   │            ▼
   └──────→ TYPE 2 DM
               │
               ▼
         HYPERGLYCEMIA

🔷 METABOLIC SYNDROME (IDF Criteria)

CENTRAL OBESITY (Waist ♂ > 90cm, ♀ > 80cm in Asians)
                    PLUS any TWO of:
    ┌─────────────────────────────────────────┐
    │ ↑ Triglycerides: ≥ 150 mg/dL           │
    │ ↓ HDL: < 40 (♂) / < 50 (♀) mg/dL      │
    │ ↑ BP: ≥ 130/85 mmHg                     │
    │ ↑ Fasting glucose: ≥ 100 mg/dL         │
    └─────────────────────────────────────────┘

PATHOPHYSIOLOGY FLOWCHART:
Obesity → Insulin Resistance
              │
    ┌─────────┴──────────┐
    ▼                    ▼
↑ Hepatic             ↑ VLDL-TG
  glucose output       secretion
    │                    │
    ▼                    ▼
Hyperglycemia        Dyslipidemia
    │                    │
    └─────────┬──────────┘
              ▼
    Endothelial dysfunction
              ▼
    ATHEROSCLEROSIS → CVD

• ↑ Insulin resistance → T2DM
• ↑ VLDL → Hypertriglyceridemia
• ↓ HDL (via CETP activity)
• ↑ LDL (small dense LDL - most atherogenic)
• ↑ Uric acid → Gout
• ↑ CRP, IL-6 → Chronic inflammation
• NAFLD → NASH → Cirrhosis

Q47. Eicosanoids - Biochemistry, Functions & Therapeutic Applications

🔷 FLOWCHART: Eicosanoid Synthesis

MEMBRANE PHOSPHOLIPIDS (Arachidonic acid at C2)
              │
              │ [Phospholipase A₂] ← triggered by Ca²⁺, injury
              │ ★ INHIBITED by Corticosteroids (↑ Lipocortin)
              ▼
    ARACHIDONIC ACID (20C, ω-6 PUFA)
         │              │
         ▼              ▼
   COX PATHWAY    LIPOXYGENASE PATHWAY
   (Cyclooxygenase)   (5-LOX)
         │              │
    ┌────┴───┐          ▼
    ▼        ▼      5-HPETE
  COX-1    COX-2        │
(constitutive) (inducible)   ▼
    │        │      LEUKOTRIENES
    └────┬───┘    LTA₄ → LTB₄ (chemotaxis)
         ▼        LTA₄ → LTC₄, LTD₄, LTE₄
      PGG₂            (bronchoconstriction)
         │
    [Peroxidase + GSH]
         ▼
      PGH₂ (unstable intermediate)
         │
    ┌────┼────┬─────────┐
    ▼    ▼    ▼         ▼
  PGI₂  PGE₂ PGF₂α    TXA₂
(PGI₂ = Prostacyclin)

🔷 FUNCTIONS TABLE

★ PGI₂ vs TXA₂ = physiological antagonists - critical exam point!

🔷 THERAPEUTIC APPLICATIONS & INHIBITORS

ASPIRIN:
  → Irreversibly acetylates COX-1 & COX-2
  → ↓ TXA₂ (anti-platelet, anticoagulant)
  → ↓ PGs (analgesic, antipyretic, anti-inflammatory)
  
NSAIDs (Ibuprofen, Naproxen):
  → Reversibly inhibit COX-1 & COX-2
  → Risk: Peptic ulcer (↓ PGE₂ gastroprotection)
  
Selective COX-2 inhibitors (Celecoxib):
  → Spares COX-1 → ↓ GI side effects
  → Risk: ↑ thrombosis (↓ PGI₂, TXA₂ preserved)
  
Corticosteroids (Dexamethasone):
  → Induce Lipocortin → inhibit Phospholipase A₂
  → ↓ ALL eicosanoids
  
5-LOX inhibitors (Zileuton):
  → ↓ Leukotriene synthesis → used in asthma
  
Leukotriene receptor antagonists (Montelukast):
  → Block LTD₄ receptor → used in asthma, allergic rhinitis

• Misoprostol (PGE₁ analogue) → prevents NSAID ulcers, cervical ripening
• Dinoprostone (PGE₂) → induces labor
• Carboprost (PGF₂α) → postpartum hemorrhage
• Epoprostenol (PGI₂) → pulmonary hypertension

Q48. Ammonia Formation, Transport, Transamination & Deamination

🔷 FLOWCHART: Ammonia Formation

AMINO ACIDS (from protein catabolism)
         │
    ┌────┴──────────────────────┐
    ▼                           ▼
TRANSAMINATION              OXIDATIVE DEAMINATION
(Aminotransferases)         (Glutamate Dehydrogenase)
    │                           │
    │ Amino group → α-KG        │ Glutamate → α-KG + NH₃
    ↓                           ↓
GLUTAMATE                   FREE NH₃
    │                           │
    └───────────────────────────┘
                   ▼
    GLUTAMINE (non-toxic transport form)
    [Glutamine synthetase, ATP-requiring]
                   ▼
         Transported to LIVER

🔷 TRANSAMINATION

α-AMINO ACID + α-KETO ACID
         ↕  [Aminotransferase + PLP (Vit B₆)]
α-KETO ACID + α-AMINO ACID

Key enzymes:
• ALT (GPT): Alanine + α-KG ⇌ Pyruvate + Glutamate
  [Liver specific → ↑ in liver disease]
  
• AST (GOT): Aspartate + α-KG ⇌ OAA + Glutamate
  [Liver + cardiac → ↑ in MI and liver disease]

Coenzyme: Pyridoxal Phosphate (PLP) → Vitamin B₆
Mechanism: PING-PONG (bi-bi) mechanism

🔷 OXIDATIVE DEAMINATION

GLUTAMATE
    ↕  [Glutamate Dehydrogenase (GDH), mitochondria]
    ↕  Cofactor: NAD⁺ or NADP⁺
α-KETOGLUTARATE + NH₃ + NADH

Regulation of GDH:
  ACTIVATED by: ADP, Leucine, GDP
  INHIBITED by: ATP, GTP, NADH (energy-rich state)

🔷 AMMONIA TRANSPORT TO LIVER

MUSCLE & PERIPHERAL TISSUES
            │
    ┌───────┴────────────┐
    ▼                    ▼
GLUTAMINE ROUTE     ALANINE ROUTE
(brain, muscle,     (muscle via
 intestine)          glucose-alanine cycle)
    │                    │
NH₃ + Glutamate     Pyruvate + NH₃
    ↓ [Glutamine      ↓ [ALT + PLP]
    synthetase]      ALANINE
    GLUTAMINE             │
    │                     │
    └─────────────────────┘
               ↓ Portal vein
           LIVER
               ↓
         UREA CYCLE
               ↓
          Urea → Kidney → Urine

★ Brain removes NH₃ primarily via glutamine synthetase (no urea cycle in brain) ★ Intestinal bacteria generate NH₃ from urea → enters portal blood

Q49. Urea Cycle - Regulation & Associated Disorders

🔷 UREA CYCLE DIAGRAM

          MITOCHONDRIAL MATRIX
    NH₃ + CO₂ + 2 ATP
          │
          ▼ [CPS-I + N-Acetylglutamate (NAG) as activator]
    CARBAMOYL PHOSPHATE
          │
          ▼ [OTC - Ornithine Transcarbamylase]
    ORNITHINE + Carbamoyl-PO₄ → CITRULLINE
                                    │
                               [Antiporter] → exits mitochondria
                                    │
          ═════════════════════ CYTOSOL ══════════════════
                                    │
    ASPARTATE + CITRULLINE          │
          │ [Argininosuccinate Synthetase + ATP]
          ▼
    ARGININOSUCCINATE
          │ [Argininosuccinate Lyase]
          ▼
    ARGININE + FUMARATE
          │             ↓
          │    Fumarate → Malate → OAA → Aspartate
          │         (links urea cycle to TCA)
          ▼ [Arginase (Liver)]
    ORNITHINE + UREA
          │               │
          │               ▼
    re-enters       UREA in blood (BUN)
    mitochondria         ↓
                    Kidney → Urine

🔷 REGULATION

KEY REGULATOR: N-ACETYLGLUTAMATE (NAG)
  • Activates CPS-I (rate-limiting enzyme)
  • NAG made by NAG Synthase
  • NAG Synthase activated by: Arginine, high protein intake

SUBSTRATE SUPPLY regulation:
  • High protein diet → ↑ urea cycle enzymes (induction)
  • Starvation → ↑ enzyme activity (more AA catabolism)
  
HORMONES:
  • Glucagon → ↑ urea cycle (more gluconeogenesis → more AA used)
  • Insulin → ↓ urea cycle

🔷 UREA CYCLE DISORDERS (Hyperammonemia)

┌──────────────────┬───────────────────┬──────────────────┐
│ ENZYME DEFECT    │ ACCUMULATED       │ KEY FEATURE      │
├──────────────────┼───────────────────┼──────────────────┤
│ CPS-I            │ NH₃ ↑             │ No orotic acid   │
├──────────────────┼───────────────────┼──────────────────┤
│ OTC (X-linked,   │ NH₃ ↑, Orotic    │ ↑ Orotic acid    │
│ most common)     │ acid ↑            │ in urine ★       │
├──────────────────┼───────────────────┼──────────────────┤
│ Arg-succinate    │ Citrulline ↑      │ Citrullinemia    │
│ Synthetase       │                   │                  │
├──────────────────┼───────────────────┼──────────────────┤
│ Arg-succinate    │ Argininosuccinate │ Argininosuccinic │
│ Lyase            │ in urine          │ aciduria         │
├──────────────────┼───────────────────┼──────────────────┤
│ Arginase         │ Arginine ↑        │ Spastic diplegia │
├──────────────────┼───────────────────┼──────────────────┤
│ NAG Synthase     │ NH₃ ↑             │ Responds to      │
│                  │                   │ Carglumic acid   │
└──────────────────┴───────────────────┴──────────────────┘

SYMPTOMS of Hyperammonemia:
  Tremors → Slurred speech → Somnolence →
  Vomiting → Cerebral edema → Coma → Death

TREATMENT:
  • Low protein diet
  • Sodium benzoate (→ hippurate, excretes 1N)
  • Sodium phenylbutyrate (→ phenylacetylglutamine, excretes 2N)
  • Arginine/Citrulline supplementation
  • Lactulose (↓ intestinal NH₃ absorption)
  • Liver transplantation

Q50. Glycine Metabolism & Metabolic Disorders

🔷 FLOWCHART: Glycine Metabolism

SOURCES OF GLYCINE:
  Serine ──→ GLYCINE ←── Threonine
  Glyoxylate             Choline
  (via transamination)
  
GLYCINE (simplest amino acid, non-essential)
         │
    ┌────┼────────┬──────────┬──────────┬─────────────┐
    ▼    ▼        ▼          ▼          ▼             ▼
SERINE  BILE  CREATINE  GLUTATHIONE  HEME       PURINE
        ACIDS  (+ Arg,     (+ Glu,   SYNTHESIS  SYNTHESIS
               Met)        Cys)     (succinyl    (C4, C5
                                     CoA)        of ring)
                │
    GLYCINE CONJUGATION:
    • Benzoate + Glycine → HIPPURATE (excreted in urine)
    • Bile acids + Glycine → Glycocholic acid
    
CATABOLISM:
    Glycine → [Glycine decarboxylase complex - 4 proteins]
            → CO₂ + NH₃ + CH₂=THF (methylene-THF)
            → feeds one-carbon pool
            
    Glycine ↔ Serine [Serine hydroxymethyltransferase + THF + Vit B₆]

🔷 METABOLIC DISORDERS OF GLYCINE

┌─────────────────────────────────────────────────────────┐
│ 1. NON-KETOTIC HYPERGLYCINEMIA (NKH)                    │
│    • Defect: Glycine decarboxylase complex (P,H,T,L)    │
│    • Accumulation: Glycine in blood + CSF               │
│    • Features: Neonatal seizures, hypotonia, apnea      │
│    • CSF:Plasma glycine ratio > 0.08 (diagnostic)       │
│    • Neonatal lethal form most common                    │
└─────────────────────────────────────────────────────────┘

┌─────────────────────────────────────────────────────────┐
│ 2. PRIMARY HYPEROXALURIA TYPE 1 (PH1)                   │
│    • Defect: Alanine-glyoxylate aminotransferase (AGT)  │
│    • Glyoxylate → Oxalate (instead of glycine)          │
│    • Features: Calcium oxalate kidney stones,           │
│      nephrocalcinosis, renal failure                     │
│    • Organs: Liver peroxisomal enzyme                   │
└─────────────────────────────────────────────────────────┘

┌─────────────────────────────────────────────────────────┐
│ 3. SARCOSINEMIA                                         │
│    • Defect: Sarcosine dehydrogenase                    │
│    • Sarcosine (N-methylglycine) accumulates            │
│    • Relatively benign                                  │
└─────────────────────────────────────────────────────────┘

┌─────────────────────────────────────────────────────────┐
│ 4. IMINOGLYCINURIA                                      │
│    • Defect: Shared renal transporter for               │
│      Glycine + Proline + Hydroxyproline                 │
│    • Benign condition - found on urine analysis         │
└─────────────────────────────────────────────────────────┘

• Glycine receptors in spinal cord (strychnine blocks them → convulsions)
• Also excitatory co-agonist at NMDA receptors in brain

Q51. Creatine & Glutathione Synthesis, Functions & Clinical Significance

🔷 CREATINE SYNTHESIS FLOWCHART

STEP 1 (Kidney):
    ARGININE + GLYCINE
          ↓ [Transamidinase / Glycine amidinotransferase]
    GUANIDINOACETATE + ORNITHINE

STEP 2 (Liver):
    GUANIDINOACETATE + S-Adenosylmethionine (SAM)
          ↓ [Guanidinoacetate methyltransferase]
    CREATINE + S-Adenosylhomocysteine (SAH)
          │
          ↓ [Creatine kinase, in muscle]
    CREATINE + ATP ⇌ PHOSPHOCREATINE (PCr) + ADP
          │
          ↓ [Non-enzymatic, spontaneous]
    CREATININE (excreted in urine at constant rate)

🔷 FUNCTIONS OF CREATINE

PHOSPHOCREATINE (PCr):
  • Immediate energy reserve in muscle & brain
  • PCr + ADP → Creatine + ATP [Creatine kinase]
  • 1st energy source in explosive, short-duration exercise
  • Replenished by ATP during rest

CREATININE:
  • Waste product of creatine metabolism
  • Excreted by glomerular filtration
  • Normal: 0.6-1.2 mg/dL (serum)
  • Used as marker of GFR / renal function
  • Constant production → reliable indicator

🔷 CLINICAL SIGNIFICANCE OF CREATINE

↑ Serum Creatinine:
  → Acute Kidney Injury (AKI)
  → Chronic Kidney Disease (CKD)
  → Rhabdomyolysis (muscle destruction)

↑ CK (Creatine Kinase) isoenzymes:
  • CK-MM → Skeletal muscle damage
  • CK-MB → Myocardial infarction
  • CK-BB → Brain injury

Creatine deficiency syndromes:
  • AGAT deficiency (Step 1 enzyme)
  • GAMT deficiency (Step 2 enzyme)
  • Creatine transporter defect (SLC6A8)
  → Features: Intellectual disability, seizures, 
    absent creatine on MR spectroscopy

🔷 GLUTATHIONE SYNTHESIS FLOWCHART

STEP 1:
    GLUTAMATE + CYSTEINE + ATP
          ↓ [γ-Glutamylcysteine synthetase]
           ↓ RATE-LIMITING STEP
    γ-GLUTAMYLCYSTEINE + ADP + Pi

STEP 2:
    γ-GLUTAMYLCYSTEINE + GLYCINE + ATP
          ↓ [Glutathione synthetase]
    GLUTATHIONE (GSH) - TRIPEPTIDE
          (γ-Glu – Cys – Gly)

🔷 GLUTATHIONE FUNCTIONS

GLUTATHIONE (GSH) - REDUCED FORM [Active]
         │
    ┌────┼──────────────────────────┐
    ▼    ▼                          ▼
ANTIOXIDANT  DETOXIFICATION    AMINO ACID
    │        (Phase II drug    TRANSPORT
    │         metabolism)      (γ-GT cycle)
    ▼
2 GSH + H₂O₂ → GSSG + 2H₂O
[Glutathione Peroxidase + Se]
    │
    ▼
GSSG (oxidized) + NADPH + H⁺
    ↓ [Glutathione Reductase]
2 GSH + NADP⁺
(NADPH from HMP shunt / PPP)

OTHER FUNCTIONS:
• Maintains protein -SH groups (prevents oxidation)
• Conjugates with xenobiotics → mercapturic acid excretion
• Leukotriene synthesis (LTC₄, LTD₄, LTE₄)
• Maintains RBC integrity

🔷 CLINICAL SIGNIFICANCE OF GLUTATHIONE

┌──────────────────────────────────────────────────────┐
│ 1. G6PD DEFICIENCY                                   │
│    ↓ NADPH → ↓ GSH → ↑ oxidative hemolysis          │
│    Triggered by: Primaquine, Dapsone, Fava beans     │
│    → Heinz bodies, Bite cells on smear               │
└──────────────────────────────────────────────────────┘

┌──────────────────────────────────────────────────────┐
│ 2. ACETAMINOPHEN TOXICITY                            │
│    Paracetamol → NAPQI (toxic metabolite)            │
│    GSH neutralizes NAPQI                             │
│    Overdose → GSH depleted → hepatic necrosis        │
│    Treatment: N-Acetylcysteine (NAC) → replenishes   │
│    GSH precursor (cysteine)                          │
└──────────────────────────────────────────────────────┘

┌──────────────────────────────────────────────────────┐
│ 3. γ-GLUTAMYL TRANSPEPTIDASE (GGT) - Lab marker     │
│    ↑ GGT in: Alcoholic liver disease, cholestasis,  │
│    enzyme induction by alcohol                       │
└──────────────────────────────────────────────────────┘

┌──────────────────────────────────────────────────────┐
│ 4. GLUTATHIONE SYNTHETASE DEFICIENCY                 │
│    → 5-Oxoprolinuria (pyroglutamic aciduria)         │
│    → Hemolytic anemia + metabolic acidosis           │
└──────────────────────────────────────────────────────┘

📌 EXAM QUICK RECALL TABLE

Source: Lippincott's Illustrated Reviews Biochemistry 8th Ed, Harper's Illustrated Biochemistry 32nd Ed