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🔥 BIOCHEMISTRY COMPETITION EXAM NOTES

One-Day High-Yield Master Study Guide

Special Focus: ⭐⭐⭐⭐⭐ Priority Topics

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⭐⭐⭐⭐⭐ TOPIC 1: REGULATION OF BLOOD GLUCOSE LEVELS

KEY CONCEPT (Score Line: "The Liver is the Glucose Bank of the Body")

Mnemonic (Hindi): "MANIK ne GLUCOSE BANK khola" - Manik = Maintains glucose; Glycogen synthesis, Lysis, Urea, Conjugation, Overall homeostasis via pancreas, Sensitivity of liver to insulin

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Normal Blood Glucose Range

• Fasting: 70-100 mg/dL (3.9-5.6 mmol/L)
• Postprandial (2h): < 140 mg/dL
• Hypoglycemia: < 70 mg/dL
• Hyperglycemia (DM): > 126 mg/dL fasting

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FLOWCHART: Blood Glucose Regulation

BLOOD GLUCOSE RISES (fed state)
         |
    Pancreatic β-cells
         |
    ↑ INSULIN secretion
         |
    ┌────────────────────────┐
    │   Insulin Actions       │
    │  • ↑ Glycogen synthesis │
    │  • ↑ Glycolysis         │
    │  • ↑ Fatty acid synth   │
    │  • ↑ Protein synthesis  │
    │  • ↓ Gluconeogenesis    │
    │  • ↓ Glycogenolysis     │
    └────────────────────────┘
         |
    Glucose stored as glycogen/fat
    Blood glucose → NORMAL

═══════════════════════════════

BLOOD GLUCOSE FALLS (fasting)
         |
    Pancreatic α-cells
         |
    ↑ GLUCAGON secretion
    + ↑ Cortisol, Epinephrine, GH (counter-regulatory)
         |
    ┌────────────────────────┐
    │   Glucagon Actions      │
    │  • ↑ Glycogenolysis     │
    │  • ↑ Gluconeogenesis    │
    │  • ↑ Fatty acid oxidation│
    │  • ↓ Glycogen synthesis │
    │  • ↓ Glycolysis         │
    └────────────────────────┘
         |
    Glucose released into blood
    Blood glucose → NORMAL

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KEY ENZYMES REGULATED (Exam Favorite!)

Mnemonic: "RISHIKA PICKS FATS ALWAYS" for Insulin actions:

• R - aReinforces glycogen synthesis
• I - Increases glycolysis
• S - Stimulates protein synthesis
• H - HMP shunt increases
• I - Inhibits gluconeogenesis
• K - Ketogenesis is suppressed
• A - Activates FA synthesis

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KEY KINASES (Two Master Switches)

1. cAMP-dependent Protein Kinase A (PKA) - activated by glucagon/epinephrine → phosphorylates enzymes → activates glycogenolysis, gluconeogenesis
2. AMP-activated Protein Kinase (AMPK) - activated when energy is low (↑AMP) → stimulates FA oxidation, inhibits FA synthesis

Memory trick: "PKA = Paisa Kam Ata (cAMP ke baad)" = When glucagon signals (low glucose) → PKA activated

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LIVER'S UNIQUE ROLE

• Glucose-6-phosphatase present ONLY in liver and kidney → can export free glucose to blood
• Liver = "glucose thermostat" of body
• Glucose transporter GLUT-2 in liver - high Km, not saturated → acts as glucose sensor

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COUNTER-REGULATORY HORMONES (SHEG Mnemonic):

• S - Somatostatin (inhibits both insulin & glucagon)
• H - HGH (Growth Hormone) - insulin antagonist
• E - Epinephrine - activates glycogenolysis
• G - Glucocorticoids (Cortisol) - promotes gluconeogenesis

Hindi Mnemonic: "SHUBHAM had SHEG" = Shubham lost glucose control, needed SHEG hormones to rescue!

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⭐⭐⭐⭐⭐ TOPIC 2: BETA OXIDATION OF FATTY ACIDS & DISORDERS

KEY CONCEPT: "CAFE → Energy"

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FLOWCHART: Beta Oxidation

FATTY ACID (cytoplasm)
         |
    Fatty acyl-CoA synthetase (+ ATP, CoA)
         |
    Fatty acyl-CoA (outer mitochondrial membrane)
         |
    CPT-I (Carnitine Palmitoyl Transferase-I)
    [RATE-LIMITING STEP]
    Inhibited by: MALONYL-CoA
         |
    Fatty acyl-CARNITINE crosses inner membrane
    (via Carnitine-acylcarnitine TRANSLOCASE)
         |
    CPT-II releases fatty acyl-CoA inside
         |
    ═══ INSIDE MITOCHONDRIA ═══
         |
    STEP 1: Acyl-CoA Dehydrogenase
            → Trans-enoyl-CoA + FADH₂
         |
    STEP 2: Enoyl-CoA Hydratase
            → 3-L-Hydroxyacyl-CoA
         |
    STEP 3: 3-Hydroxyacyl-CoA Dehydrogenase
            → 3-Ketoacyl-CoA + NADH
         |
    STEP 4: Thiolase (cleavage)
            → Acetyl-CoA + shorter Fatty acyl-CoA
         |
    (Cycle repeats with shorter chain)
         |
    Final product: All ACETYL-CoA
         |
         ↓
    TCA Cycle → ATP synthesis
    OR
    Ketone body synthesis (in liver)

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ATP YIELD (Palmitic acid C16:0 - Exam Favorite!)

Formula: For C16 fatty acid = 7 cycles of beta oxidation

Mnemonic: "DIVYA earns 106" - Divya studied hard for 7 rounds, earned 106 marks!

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PEROXISOMAL vs MITOCHONDRIAL Beta Oxidation

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KEY DISORDERS OF BETA OXIDATION

1. Refsum Disease

• Defect: Phytanoyl-CoA hydroxylase deficiency
• Problem: Cannot oxidize phytanic acid (branched chain FA from green vegetables/dairy)
• Accumulates: Phytanic acid (3-methyl branched)
• Clinical: Retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, anosmia, deafness
• Mnemonic: "RADHIKA smells nothing, sees nothing" - Radhika = Refsum, anosmia + retinitis pigmentosa

2. Zellweger Syndrome (Cerebrohepatorenal Syndrome)

• Defect: Absent/dysfunctional peroxisomes (PEX gene mutations)
• Problem: Cannot import proteins into peroxisomes
• Clinical: Facial dysmorphism, hypotonia, seizures, liver dysfunction, death in infancy
• Key finding: Very long chain fatty acids (VLCFA) accumulate in blood
• Mnemonic: "SHUBHAM has no PEROXY" - Shubham's peroxisomes are gone → Zellweger

3. MCAD Deficiency (Medium-Chain Acyl-CoA Dehydrogenase)

• Defect: Cannot oxidize C6-C12 fatty acids
• Clinical: Hypoketotic hypoglycemia during fasting, vomiting, lethargy → sudden death
• = Jamaican Vomiting Sickness (similar mechanism)
• Jamaican Vomiting Sickness: Due to hypoglycin A in unripe ackee fruit → inhibits MCAD
• Mnemonic: "NAMANYA vomited from Jamaica" - Namanya = No MCAD = vomiting

4. Sudden Infant Death Syndrome (SIDS)

• Associated with MCAD deficiency or other FA oxidation defects
• Infant cannot maintain blood glucose during prolonged fasting (overnight)
• Hypoketotic hypoglycemia → cardiac arrest

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⭐⭐⭐⭐⭐ TOPIC 3: AMMONIA METABOLISM & UREA CYCLE

KEY CONCEPT: "Liver is the Ammonia Garbage Collector"

NH₃ is toxic to CNS even at slightly elevated levels → must be converted to UREA (non-toxic, water-soluble, excreted in urine)

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SOURCES OF AMMONIA (Mnemonic: "MANIK gives NH3")

• M - Muscle protein catabolism (BCAA → glutamine)
• A - Amino acid transdeamination in liver
• N - kNot bacteria (intestinal bacteria via urease on urea)
• I - Intestinal glutaminase (major source!)
• K - Kidney (glutamine → NH₄⁺ for acid-base balance)

• Amines → MAO (monoamine oxidase) → NH₃
• Purines/Pyrimidines catabolism

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TRANSPORT OF AMMONIA TO LIVER (Key!)

Two main carriers:

Glutamate + NH₃ → [Glutamine synthetase] → GLUTAMINE
(All peripheral tissues, especially muscle, brain)
         ↓ (to liver)
Glutamine → [Glutaminase] → Glutamate + NH₃
(then NH₃ enters urea cycle)

Muscle: Pyruvate + Glutamate → [Transamination] → ALANINE
         ↓
    (Alanine travels to liver)
         ↓
Liver: Alanine + α-KG → Pyruvate + Glutamate → NH₃
         ↓
    Pyruvate → Gluconeogenesis → GLUCOSE (sent back to muscle)

Mnemonic: "RADHIKA carries her amino lunch to LIVER" = Radhika (ALANINE) cycles from muscle to liver

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FLOWCHART: UREA CYCLE (Diagrammatic)

╔══════════ MITOCHONDRIA ══════════╗
║                                   ║
║  NH₃ + CO₂ + 2ATP                ║
║         ↓                         ║
║   CPS-I (N-acetylglutamate)       ║
║  (Carbamoyl Phosphate Synthetase-I)║
║         ↓                         ║
║  CARBAMOYL PHOSPHATE              ║
║         ↓                         ║
║  OTC (Ornithine Transcarbamylase) ║
║  ORNITHINE → CITRULLINE           ║
║                                   ║
╚═══════════════════════════════════╝
         ↓ (Citrulline exits to cytoplasm)

╔══════════ CYTOPLASM ══════════════╗
║                                   ║
║  CITRULLINE + ASPARTATE + ATP     ║
║         ↓                         ║
║   Argininosuccinate SYNTHETASE    ║
║         ↓                         ║
║  ARGININOSUCCINATE                ║
║         ↓                         ║
║   Argininosuccinate LYASE         ║
║         ↓                         ║
║  ARGININE + FUMARATE              ║
║         ↓                         ║
║   ARGINASE (liver only!)          ║
║         ↓                         ║
║  UREA + ORNITHINE                 ║
║  (Ornithine returns to mito)      ║
║  (Urea → kidney → excreted)       ║
║                                   ║
╚═══════════════════════════════════╝

MNEMONIC for Urea Cycle Steps: "DIVYA CALLS ORNITHINE CITRULLINE ARGININE UREA"

• Ornithine + Carbamoyl-P → Citrulline (OTC, in MITO)
• Citrulline + Aspartate → Argininosuccinate
• Argininosuccinate → Arginine + Fumarate
• Arginine → Urea + Ornithine (ARGINASE)

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ENERGY COST OF UREA CYCLE

• 4 ATP equivalents consumed per urea molecule
  • 2 ATP → CPS-I step
  • 1 ATP (as AMP = 2 high-energy bonds) → argininosuccinate synthetase step

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ALLOSTERIC REGULATION

• CPS-I activated by: N-ACETYLGLUTAMATE (NAG) - obligatory activator
  • NAG is synthesized by NAG synthetase from acetyl-CoA + glutamate
  • Arginine stimulates NAG synthetase (positive feedback)
• When protein intake increases: more arginine → more NAG → more CPS-I activity → more urea synthesis

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HYPERAMMONEMIA - Causes & Features

KEY DIFFERENTIATOR:

OTC deficiency (most common UCD):

• X-linked recessive (boys affected, girls carriers)
• ↑ Orotic acid (carbamyl phosphate shunted to pyrimidine synthesis)
• Treatment: Low protein diet, sodium benzoate (binds glycine → hippurate), sodium phenylacetate (binds glutamine)

CPS-I deficiency:

• Autosomal recessive
• NO orotic acid (CPS-II not affected)
• Requires N-acetylglutamate for treatment

Mnemonic: "MANIK has OTC X-problem" - OTC = X-linked, Male affected

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CLINICAL SIGNS OF HYPERAMMONEMIA

• Lethargy, irritability
• Vomiting
• Respiratory alkalosis (early - NH₃ stimulates respiratory center)
• Cerebral edema → coma → death
• ↑ Glutamine in CSF (NH₃ + Glutamate → Glutamine, depletes α-KG → TCA cycle disrupted)

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KETONE BODY METABOLISM (⭐ Bonus - Most Repeated!)

KEY CONCEPT: "Liver makes ketones, but CANNOT use them"

SYNTHESIS (in LIVER mitochondria only)

Acetyl-CoA + Acetyl-CoA
         ↓ [Thiolase]
    Acetoacetyl-CoA
         ↓ [HMG-CoA synthase]  ← RATE-LIMITING STEP
      HMG-CoA
         ↓ [HMG-CoA lyase]
    ACETOACETATE + Acetyl-CoA
         ↓                  ↓
[β-HB dehydrogenase]  Spontaneous decarboxylation
  β-HYDROXYBUTYRATE    ACETONE (excreted in breath)

Mnemonic: "SHUBHAM MAKES HMG" = Shubham (liver) Makes HMG-CoA → ketones for others

UTILIZATION (in all tissues EXCEPT LIVER)

β-Hydroxybutyrate → [β-HB dehydrogenase] → Acetoacetate
         ↓
[Succinyl-CoA transferase (SCOT)] ← ABSENT IN LIVER!
         ↓
Acetoacetyl-CoA → 2 Acetyl-CoA → TCA cycle

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WHY LIVER CANNOT USE KETONE BODIES?

SCOT (Succinyl-CoA: Acetoacetate CoA-Transferase) is absent in hepatocytes

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KETOSIS vs KETOACIDOSIS

Mnemonic "NAMANYA DKA rule": DKA = Diabetes + Ketones + Acidosis (pH < 7.3, Bicarbonate < 15, Glucose > 250)

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QUICK REFERENCE: OTHER KEY TOPICS

FLUID MOSAIC MODEL (Singer-Nicolson 1972)

• Membrane = phospholipid bilayer (fluid) + proteins (mosaic pattern)
• Lipids can move laterally (fast) but flip-flop (slow/rare)
• Proteins: Integral (span membrane) and Peripheral (surface attached)
• Cholesterol = membrane stabilizer (regulates fluidity)

TRANSPORT ACROSS CELL MEMBRANE

Mnemonic: "DIVYA SAFI" - Simple, Active, Facilitated, Endo/exocytosis

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ENZYME CLASSIFICATION (EC Numbers - "OTH LI")

1. Oxidoreductases - redox reactions (dehydrogenases, oxidases)
2. Transferases - transfer groups (aminotransferases, kinases)
3. Hydrolases - hydrolysis (proteases, lipases, phosphatases)
4. Lyases - add/remove groups without hydrolysis (decarboxylases)
5. Isomerases - structural rearrangements (mutases, epimerases)
6. Ligases (Synthetases) - join molecules + ATP (amino acyl-tRNA synthetase)

Mnemonic: "OTHLI L" = "RADHIKA ONLY THINKS HAVING LOVELY INTELLIGENT LOOKS" = Oxido, Transfer, Hydro, Lyase, Isomerase, Ligase

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ISOENZYMES (Short Note)

• Same function, different structure/charge
• Examples: LDH (5 isoforms), CK (3 isoforms), ALP, Amylase

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ENZYME INHIBITION

Competitive vs Non-Competitive (Most asked!)

Mnemonic: "SHUBHAM COMPETES with his Km" = Competitive → Km changes, Vmax same "NAMANYA is Non-competitive, Never changes Km" = Non-competitive → Km same, Vmax decreases

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DIABETIC KETOACIDOSIS - Clinical Summary

PRECIPITANTS: Infection (most common), Omission of insulin, New DM presentation

PATHOPHYSIOLOGY:
No insulin → ↑ Glucagon
     ↓
↑ Glycogenolysis + ↑ Gluconeogenesis → HYPERGLYCEMIA
↑ Lipolysis → FFA to liver → ↑ Beta oxidation → ↑ Acetyl-CoA
     ↓
Overwhelmed TCA cycle → HMG-CoA pathway → KETONE BODIES
     ↓
Metabolic acidosis (pH <7.3, HCO₃ <15)

CLINICAL: Polyuria, polydipsia, vomiting, Kussmaul breathing,
          Fruity breath (acetone), Abdominal pain
LABS: Glucose >250, pH <7.3, Bicarbonate <15, Anion gap ↑,
      Ketonuria, Ketonemia

TREATMENT: IV fluids → Insulin → KCl replacement
           (K⁺ falls further with insulin → MUST replace!)

Mnemonic: "RADHIKA's DKA FIKA HAI" (Hindi: fika = pale/unwell)

• Fluids first
• Insulin (after K >3.5)
• K-replacement (always!)
• Acidosis correction (bicarbonate only if pH <6.9)

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GLYCOLYSIS KEY POINTS (LAQ Summary)

GLUCOSE (6C)
    ↓ Hexokinase/Glucokinase [Step 1] - irreversible, -1 ATP
    ↓ Phosphoglucoisomerase
    ↓ PFK-1 [Step 3] - RATE-LIMITING - irreversible, -1 ATP
    ↓ Aldolase
    ↓ Triose phosphate isomerase
2× Glyceraldehyde-3-P
    ↓ GAPDH (NAD+ → NADH)
    ↓ Phosphoglycerate kinase (+2 ATP each)
    ↓ Phosphoglycerate mutase
    ↓ Enolase
    ↓ Pyruvate kinase [irreversible, +2 ATP each]
2× PYRUVATE

NET: 2 ATP, 2 NADH, 2 Pyruvate

1. Hexokinase/Glucokinase → bypassed by Glucose-6-phosphatase
2. PFK-1 → bypassed by Fructose-1,6-bisphosphatase
3. Pyruvate Kinase → bypassed by PEPCK + Pyruvate carboxylase

Mnemonic: "NAMANYA HPP" = Hexokinase, PFK-1, Pyruvate kinase = 3 irreversible steps

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RAPOPORT-LUEBERING CYCLE & 2,3-BPG

• In RBC only: 1,3-BPG → 2,3-BPG (bypasses ATP generation)
• Function of 2,3-BPG: Binds to deoxyhemoglobin → decreases O₂ affinity → RIGHT SHIFT of O₂ dissociation curve → more O₂ delivery to tissues
• Increased in: High altitude, anemia, chronic hypoxia
• Decreased in: Stored blood (causes decreased O₂ delivery)

Mnemonic: "MANIK breathes at altitude, needs more 2,3-BPG"

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G6PD DEFICIENCY (Short Clinical)

• X-linked recessive (mostly males)
• HMP shunt blocked → no NADPH → no reduced glutathione → RBC vulnerable to oxidative stress
• Triggers: Primaquine, dapsone, fava beans, infection
• Clinical: Episodic hemolytic anemia, Heinz bodies, bite cells
• Mnemonic: "SHUBHAM eats FAVA, gets FAVA crisis" = favism

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HMP SHUNT (Pentose Phosphate Pathway) - Short Note

• Occurs in cytoplasm
• Oxidative phase: Glucose-6-P → Ribulose-5-P + 2 NADPH + CO₂ (G6PD is rate-limiting)
• Non-oxidative phase: Interconversions → Ribose-5-P (for nucleotides)
• Products: NADPH (antioxidant, FA synthesis) + Ribose-5-P (nucleotides)
• Active in: Liver, adrenal cortex, RBC, mammary gland, gonads (steroidogenesis needs NADPH)

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PHOSPHOLIPIDS (Short)

• Glycerophospholipids: Lecithin (PC), Cephalin (PE), Phosphatidylserine, Phosphatidylinositol
• Lecithin (PC): Major lung surfactant (L/S ratio >2 = fetal lung maturity)
• Sphingomyelin: Sphingosine + phosphocholine (myelin sheath)
• Plasmalogen: Ether-linked FA, important in myelin and heart

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LIPOPROTEINS (Quick Table)

Mnemonic: "DIVYA COMES VERY LATE" = Chylomicron (C), VLDL (V), IDL, LDL (L) = increasing density, decreasing TG

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UREA CYCLE DISORDERS - Quick Differentials

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PHENYLKETONURIA (PKU) - Clinical Short

• Defect: Phenylalanine hydroxylase (PAH) deficiency → Phe → cannot convert to Tyrosine
• Accumulates: Phenylpyruvate, phenylacetate, phenyllactate
• Clinical: Intellectual disability, seizures, fair skin, musty odor, eczema
• Screen: Guthrie test (neonatal screening)
• Treatment: Phenylalanine-restricted diet; Sapropterin (BH4 cofactor) for responsive forms
• Mnemonic: "MANIK PKU = Musty + Kehta nahi (no tyrosine synthesis)"

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GALACTOSEMIA - Clinical Short

• Classic: Galactose-1-P uridyltransferase deficiency
• Accumulates: Galactose-1-phosphate (toxic to liver, brain, lens)
• Clinical: Jaundice, liver damage, cataracts, E. coli sepsis in neonates, intellectual disability
• Treatment: Eliminate lactose and galactose from diet
• Mnemonic: "DIVYA got GALACT + Cataracts + E. coli"

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LESCH-NYHAN SYNDROME

• Defect: HGPRT (Hypoxanthine-Guanine Phosphoribosyl Transferase) - purine salvage pathway
• X-linked recessive
• Accumulates: Uric acid
• Clinical: Gout + Self-mutilation (lip/finger biting) + Intellectual disability + Choreoathetosis
• Mnemonic: "NAMANYA bites herself" = Lesch-Nyhan = self-injurious behavior

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SUMMARY SCORING SHEET - HIGH YIELD KEY WORDS

Use these words in your answers to impress the checker:

• "cAMP-dependent protein kinase cascade"
• "Glucose-6-phosphatase - hepatic glucose export"
• "F-2,6-bisphosphate - key allosteric regulator"
• "Counter-regulatory hormones"
• "AMPK - cellular energy sensor"

• "CPT-I - carnitine shuttle - rate-limiting step"
• "Malonyl-CoA inhibits CPT-I"
• "FADH₂ and NADH generated per cycle"
• "Peroxisomal vs mitochondrial oxidation"
• "Very long chain fatty acids - peroxisomal oxidation"

• "Glutamine - primary nitrogen transport molecule"
• "Alanine-glucose cycle"
• "N-acetylglutamate - obligatory activator of CPS-I"
• "OTC deficiency - X-linked - orotic acid elevated"
• "4 ATP equivalents consumed per urea molecule"
• "Arginase present in liver only"

• "HMG-CoA synthase - rate-limiting step"
• "SCOT absent in liver - cannot utilize ketone bodies"
• "Ketonemia, ketonuria, Kussmaul breathing"
• "β-hydroxybutyrate:acetoacetate ratio elevated in DKA"

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Last-minute tip (RADHIKA, NAMANYA, DIVYA, SHUBHAM, MANIK - ek team bana lo!): Each person owns one topic:

• RADHIKA = Regulation of glucose
• NAMANYA = kNockout enzymes (enzyme inhibition)
• DIVYA = DKA + ketone bodies
• SHUBHAM = Shunts (HMP, urea cycle)
• MANIK = Metabolism of amino acids (PKU, Homocystinuria)

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🔥 COMPLETE BIOCHEMISTRY MASTER NOTES

One-Day Exam Preparation - All Topics

Same Style as ⭐⭐⭐⭐⭐ Questions

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SECTION 1: CELL MEMBRANE

FLUID MOSAIC MODEL (Singer & Nicolson, 1972)

Key Concept: "Bilayer = Ocean, Proteins = Icebergs"

OUTER LEAFLET
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
 ○○○ Peripheral protein ○○○
████████████████████████████████████  ← Phospholipid heads (hydrophilic)
||||||||  Integral protein  |||||||||  ← Fatty acid tails (hydrophobic)
████████████████████████████████████  ← Phospholipid heads
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
INNER LEAFLET

Components:

Membrane Fluidity Factors:

• Increases fluidity: ↑ Temperature, ↑ Unsaturated FA (kinks prevent packing), ↓ Cholesterol (at low temp)
• Decreases fluidity: ↓ Temperature, ↑ Saturated FA, ↑ Cholesterol (at high temp = stabilizer)

Hindi Mnemonic: "MANIK ka MEMBRANE - Fluid jaise PANI" Mosaic = M, Fluid = F, Bilayer = B → MFB = Manik Full Bada (Singer-Nicolson model)

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TRANSPORT ACROSS CELL MEMBRANE

PASSIVE (No ATP)                    ACTIVE (ATP required)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Simple diffusion  │  Facilitated   │  Primary     │  Secondary
O₂, CO₂, N₂,    │  diffusion      │  Na⁺/K⁺-     │  SGLT1
ethanol, steroids │  GLUT1-4       │  ATPase       │  (Na⁺-Glucose
(small nonpolar) │  (glucose,      │  Ca²⁺-ATPase  │   cotransport)
                 │  fructose)      │  H⁺/K⁺-ATPase│
                 │  Ion channels   │               │
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
ENDOCYTOSIS (in)          EXOCYTOSIS (out)
Phagocytosis (cells)      Secretion of hormones
Pinocytosis (fluid)       Neurotransmitters
Receptor-mediated         Mucus secretion
(LDL, insulin)

GLUT Transporters (Exam Favourite!):

Mnemonic: "RADHIKA BGLNA" - Brain/RBC=GLUT1, Glucose sensor=GLUT2, Liver/Neuron=GLUT3, Nudge by insulin=GLUT4, Absorption of fructose=GLUT5

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SECTION 2: ENZYMES

CLASSIFICATION (EC Numbers)

Master Mnemonic: "OTHLI L" = "RISHIKA ONLY THINKS HAVING LOVELY INTELLIGENT LOOKS"

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MECHANISM OF ENZYME ACTION

Two Key Theories:

• Enzyme active site = rigid lock
• Substrate = specific key
• NO conformational change

• Active site changes shape to fit substrate
• Enzyme molds around substrate
• More accurate - explains broad substrate specificity

Catalytic Mechanisms:

Enzyme + Substrate → [ES Complex] → Enzyme + Product
                     ↑
              TRANSITION STATE
           (lower activation energy)

1. Proximity & orientation - brings substrates close
2. Acid-Base catalysis - H⁺ donation/acceptance (His residue)
3. Covalent catalysis - transient ES covalent bond (Ser proteases)
4. Metal ion catalysis - stabilize transition state (Zn²⁺ in carboxypeptidase)
5. Strain distortion - distorts substrate bonds

Mnemonic: "DIVYA PASSES Chemistry" = Proximity, Acid-base, Strain, Covalent, Electrostatic = enzyme mechanisms

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ENZYME KINETICS (Michaelis-Menten)

         Vmax × [S]
  V  =  ───────────
          Km + [S]

Km = substrate concentration at ½ Vmax
   = measure of enzyme-substrate AFFINITY
   = LOW Km → HIGH affinity
   = HIGH Km → LOW affinity

Vmax = maximum velocity (all active sites occupied)

1/V
 |         competitive inhibitor
 |        /
 |       /  no inhibitor
 |      /  /
 |     /  /  non-competitive inhibitor
 |    /  /  /
 |___/___/__/______________ 1/[S]
    -1/Km    0

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ENZYME INHIBITION

Competitive vs Non-Competitive

Hindi Mnemonic: "SHUBHAM COMPETES - Km badha deta hai" = Competitive → Km increases "NAMANYA NON-competitive - Vmax gira deti hai" = Non-competitive → Vmax decreases

Irreversible Inhibition:

• Covalently binds enzyme - permanent block
• Examples: Aspirin (COX), Organophosphates (AChE), Penicillin (transpeptidase)
• Requires new enzyme synthesis to recover

Uncompetitive Inhibition:

• Binds ONLY to ES complex (not free enzyme)
• Both Km AND Vmax decrease (parallel lines on Lineweaver-Burk)

---

ISOENZYMES (Short Note)

• Definition: Multiple forms of same enzyme - same function, different structure/electrophoretic mobility/organ distribution
• Clinical use: Organ-specific damage marker

"LDH-1 > LDH-2 = Heart attack" (normally LDH-2 > LDH-1 = FLIP pattern in MI) Mnemonic: "MANIK's HEART FLIPS in MI"

---

COENZYMES (Short Note)

Mnemonic: "RADHIKA's VITAMINS Never Fail" B1=TPP, B2=FAD, B3=NAD, B5=CoA, B6=PLP, B7=Biotin, B9=THF, B12=B12

---

DIAGNOSTIC IMPORTANCE OF ENZYMES

Mnemonic: "DIVYA CALLS AMBULANCE" = Diagnostic enzymes for emergency conditions

---

SECTION 3: CARBOHYDRATE CHEMISTRY & METABOLISM

GLYCOSAMINOGLYCANS (GAGs)

• N-acetyl amino sugar = GlcNAc or GalNAc
• Acidic sugar = Glucuronic acid or Iduronic acid (give negative charge)
• Heavily sulfated → strongly ANIONIC → attract water → gel consistency

Types of GAGs:

Mnemonic: "SHUBHAM's HC DKH" = Hyaluronic, Chondroitin, Dermatan, Keratan, Heparan, Heparin

MUCOPOLYSACCHARIDOSES (Lysosomal Storage Diseases):

Mnemonic: "HURLER has HORNS (corneal clouding), HUNTER HUNTS without glasses (no corneal)"

---

HOMOPOLYSACCHARIDES

Key fact: Glycogen vs Starch:

• Glycogen = MORE branched (branch every 8-10 residues)
• Amylopectin = branch every 24-30 residues
• More branches = faster glucose release = better for rapid energy

Mnemonic: "MANIK STACKS GREAT CELLULOSE" = Starch, Glycogen, Cellulose = 3 main homopolysaccharides

---

GLYCOLYSIS (LAQ)

Complete Flowchart:

GLUCOSE (C6)
  │ [1] Hexokinase / Glucokinase  ← ATP used (-1 ATP)
  │     Irreversible
  ▼
Glucose-6-Phosphate
  │ [2] Phosphoglucoisomerase
  ▼
Fructose-6-Phosphate
  │ [3] PHOSPHOFRUCTOKINASE-1 (PFK-1)  ← ATP used (-1 ATP)
  │     *** RATE-LIMITING STEP ***
  │     Activated: AMP, F-2,6-BP, insulin
  │     Inhibited: ATP, citrate, glucagon
  ▼
Fructose-1,6-Bisphosphate
  │ [4] Aldolase
  ▼
Dihydroxyacetone-P + Glyceraldehyde-3-P (DHAP ⇌ G3P)
  │ [5] Triosephosphate isomerase
  ▼
2× Glyceraldehyde-3-Phosphate
  │ [6] GAPDH (NAD⁺→NADH)  ← NAD⁺ required!
  ▼
2× 1,3-Bisphosphoglycerate
  │ [7] Phosphoglycerate kinase  → +2 ATP (×2 = +4 ATP)
  │     [SUBSTRATE-LEVEL PHOSPHORYLATION]
  ▼
2× 3-Phosphoglycerate
  │ [8] Phosphoglycerate mutase
  ▼
2× 2-Phosphoglycerate
  │ [9] Enolase  (inhibited by Fluoride!)
  ▼
2× Phosphoenolpyruvate (PEP)
  │ [10] PYRUVATE KINASE  → +2 ATP (×2 = +4 ATP)
  │      Irreversible | Activated: F-1,6-BP | Inhibited: ATP, Alanine
  ▼
2× PYRUVATE

NET: -2 ATP + 4 ATP = +2 ATP
      2 NADH (used in ETC = +5 ATP aerobically)

3 IRREVERSIBLE STEPS (bypassed in Gluconeogenesis):

GLYCOLYSIS          GLUCONEOGENESIS BYPASS
Hexokinase     →    Glucose-6-phosphatase (liver/kidney only!)
PFK-1          →    Fructose-1,6-bisphosphatase
Pyruvate kinase →   Pyruvate carboxylase + PEPCK

Mnemonic: "NAMANYA HPP bypass krti hai" = Hexokinase, PFK-1, Pyruvate kinase = the 3 irreversible ones

---

GLUCONEOGENESIS

Gluconeogenic Precursors (LAMP Mnemonic):

• L - Lactate (from muscle, RBC via Cori cycle)
• A - Amino acids (glucogenic: Ala, Glu, Asp etc.) - especially ALANINE
• M - "M" glycerol (from triglyceride breakdown in adipose)
• P - Propionate (odd-chain FA → succinyl-CoA → OAA)

Hindi Mnemonic: "DIVYA ke LAMP se Glucose bana" = Lactate, Alanine, glycerol (M), Propionate

Key Unique Enzymes:

Cori Cycle:

MUSCLE:                    LIVER:
Glucose → Lactate  →→→→→  Lactate → Glucose
(anaerobic glycolysis)      (gluconeogenesis)
         ←←←←←←←←←←←←←←
               Blood
Cost: 2 ATP in muscle, 6 ATP in liver

Mnemonic: "SHUBHAM goes CORI way - Muscle deta hai, Liver lata hai"

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GLYCOGEN METABOLISM & ITS REGULATION (LAQ)

GLYCOGEN SYNTHESIS:

Glucose → G-6-P → G-1-P
                     ↓ UTP + Glucose-1-P
                   UDP-Glucose  [UDP-glucose pyrophosphorylase]
                     ↓
               Added to glycogen chain [Glycogen synthase] ← KEY ENZYME
                     ↓ (when chain >11 residues)
               Branching enzyme (α-1,4 → α-1,6 bonds every 8-10 residues)

GLYCOGENOLYSIS (Breakdown):

Glycogen
  ↓ [Glycogen phosphorylase] ← RATE-LIMITING
    (requires Vit B6/PLP as cofactor!)
G-1-P → G-6-P → Glucose (via G-6-Phosphatase in LIVER)
                → Stays in muscle (no G-6-Phosphatase in MUSCLE)

Debranching enzyme:
  - Transfers 3 of 4 residues at branch → new chain (transferase activity)
  - Cleaves last residue at α-1,6 bond → free glucose (glucosidase activity)

REGULATION (Most Important!):

GLUCAGON/EPINEPHRINE (fasting/stress)
         ↓
    ↑ cAMP → Protein Kinase A (PKA)
         ↓
    Phosphorylates:
    ┌──────────────────────┐
    │ Glycogen PHOSPHORYLASE b → a (ACTIVE)    ↑ GLYCOGENOLYSIS
    │ Glycogen SYNTHASE I → D (INACTIVE)       ↓ SYNTHESIS
    └──────────────────────┘

INSULIN (fed state)
         ↓
    Activates Protein Phosphatase
         ↓
    Dephosphorylates:
    ┌──────────────────────┐
    │ Glycogen PHOSPHORYLASE a → b (INACTIVE)  ↓ GLYCOGENOLYSIS
    │ Glycogen SYNTHASE D → I (ACTIVE)         ↑ SYNTHESIS
    └──────────────────────┘

KEY RULE: "Phosphorylation ACTIVATES phosphorylase but INACTIVATES synthase" Mnemonic: "RADHIKA's PHOSPHO rule: Phospho = Phoda (breaks) glycogen"

Glycogen Storage Diseases:

Mnemonic: "VERY POOR CARB DIET MAKES HEALTH BAD" = Von Gierke, Pompe, Cori, Anderson, McArdle, Hers

---

HMP SHUNT (Pentose Phosphate Pathway) - Short Note

Two Phases:

OXIDATIVE PHASE (irreversible):
Glucose-6-P
  ↓ [G6PD] ← RATE-LIMITING (needs NADP⁺)
6-Phosphogluconolactone + NADPH
  ↓ [6-Phosphogluconate dehydrogenase]
Ribulose-5-P + CO₂ + NADPH
(2 NADPH produced per cycle)

NON-OXIDATIVE PHASE (reversible):
Ribulose-5-P ⇌ Ribose-5-P (via isomerase)
Transketolase + Transaldolase shuffle carbons
→ F-6-P and G-3-P (re-enter glycolysis)

Products & Their Uses:

Mnemonic: "SHUBHAM's HMP = NADPH for Nailing Defense"

---

GALACTOSE METABOLISM - Short Note

Dietary Lactose
  ↓ [Lactase]
Glucose + GALACTOSE
  ↓ [Galactokinase]  ← uses ATP
Galactose-1-Phosphate
  ↓ [Galactose-1-P Uridyltransferase (GALT)] ← KEY ENZYME
  + UDP-Glucose
Glucose-1-P + UDP-Galactose
  ↓ [UDP-Galactose-4-epimerase]
UDP-Glucose (recycled)
  ↓
Glucose-1-P → Glycolysis

Galactosemia Types:

Treatment: Eliminate galactose and lactose from diet Mnemonic: "DIVYA GALT problem = JAUNDICE + CATARACTS + E. coli"

---

SECTION 4: LIPID CHEMISTRY & METABOLISM

PHOSPHOLIPIDS

Structure:

              Polar head group (choline/ethanolamine/serine/inositol)
              |
         ┌────┴────┐
         │ GLYCEROL │
         └─┬──┬──┬─┘
           │  │  │
           FA  FA  Phosphate-head
         (sn-1)(sn-2)(sn-3)

sn-2 position usually = UNSATURATED fatty acid (arachidonic acid source!)

Major Types:

Lung maturity = L/S ratio >2.0 (Lecithin:Sphingomyelin) Mnemonic: "SHUBHAM's LUNG = L/S 2 se zyada = Safe delivery"

---

GLYCOSPHINGOLIPIDS

Mnemonic: "RADHIKA GETS TIRED" = Gaucher, Krabbe, Tay-Sachs = storage diseases

Key Storage Diseases:

Mnemonic: "NAMANYA GETS NEW FABRICS = Niemann, Gaucher, Tay-sachs, Krabbe, Fabry"

---

FATTY ACID SYNTHESIS

Key Steps:

STEP 1: Acetyl-CoA escapes mitochondria as CITRATE
Acetyl-CoA + OAA → Citrate (in mito)
Citrate → cytoplasm → ATP citrate lyase → Acetyl-CoA + OAA

STEP 2: ACETYL-CoA CARBOXYLASE (ACC) ← RATE-LIMITING STEP
Acetyl-CoA + CO₂ + ATP + BIOTIN → MALONYL-CoA
Activated by: Citrate, Insulin
Inhibited by: Palmitoyl-CoA (product), Glucagon, AMPK

STEP 3: Fatty Acid Synthase (FAS) - 7 reactions repeat
Starting: 1 Acetyl-CoA + 7 Malonyl-CoA
Each cycle: adds 2C to chain
→ PALMITATE (C16) as final product

FA Synthesis vs Beta Oxidation (Comparison Table - Exam Favourite!):

Mnemonic: "DIVYA SYNTHESIZES in CYTOPLASM, BURNS in MITOCHONDRIA"

---

CHOLESTEROL METABOLISM

Synthesis (HMG-CoA Pathway):

Acetyl-CoA + Acetyl-CoA
  ↓ [Thiolase]
Acetoacetyl-CoA
  ↓ [HMG-CoA synthase] (cytoplasm - different from mito for ketones!)
HMG-CoA (3-Hydroxy-3-methylglutaryl-CoA)
  ↓ [HMG-CoA REDUCTASE] ← RATE-LIMITING STEP ← Statin target!
Mevalonate
  ↓ (several steps)
Squalene → Lanosterol → CHOLESTEROL

Regulation of HMG-CoA Reductase:

• Activated/expressed more: Low cholesterol, Insulin
• Inhibited/degraded: High cholesterol (SREBP-2 pathway), Glucagon, Statins
• Phosphorylated (inactive) by AMPK when energy low
• Dephosphorylated (active) by insulin

Cholesterol Functions:

• Membrane fluidity regulator
• Precursor: Bile acids, Steroid hormones (cortisol, sex hormones), Vitamin D
• Carried in blood by lipoproteins

Cholesterol Transport:

LIVER → VLDL → IDL → LDL → Peripheral tissues
                ↑
         LDL receptor (ApoB-100 recognized)
         Defective in FAMILIAL HYPERCHOLESTEROLEMIA

Reverse Cholesterol Transport:
Peripheral tissues → HDL → Liver (via CETP)
ApoA-I activates LCAT (converts free cholesterol → cholesteryl ester)

Mnemonic: "MANIK's STATIN stops HMG-CoA Reductase = Lower cholesterol"

---

LIPOTROPIC FACTORS & FATTY LIVER - Short Note

Lipotropic Factors = Substances that PREVENT fat accumulation in liver

Fatty Liver (Hepatic Steatosis):

1. Excess alcohol → ↑ NADH → ↓ FA oxidation + ↑ FA synthesis → fat accumulates
2. Protein malnutrition (Kwashiorkor) → ↓ Choline/Apo-B → VLDL export fails
3. Obesity, diabetes, NASH
4. CCl₄ poisoning → damages ER → blocks VLDL export

Mnemonic: "SHUBHAM's CHOLINE saves his LIVER from FAT - Choline + Methionine = Lipotrohic team"

---

SECTION 5: PROTEIN CHEMISTRY & METABOLISM

PLASMA PROTEINS

Normal Values & Functions:

Acute Phase Proteins:

• Positive (increase): CRP, Fibrinogen, Haptoglobin, Ferritin, α₁-Antitrypsin, Ceruloplasmin
• Negative (decrease): Albumin, Transferrin, Prealbumin

Mnemonic: "RADHIKA's CRP FIERCELY rises" = CRP, Fibrinogen, Inflammation markers rise in acute phase

---

AMINO ACID CLASSIFICATION

By Nutritional Requirement:

• Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, a-Arginine (semi), Lysine, Leucine

By R-group (Side chain):

Mnemonic: "LILLY is Ketogenic" = Leucine + Lysine = ONLY ketogenic AAs

---

STRUCTURAL CLASSIFICATION OF PROTEINS

Special Structures:

• α-helix: Right-handed; 3.6 residues/turn; proline BREAKS helix
• β-sheet: Parallel or antiparallel; H-bonds between strands
• Triple helix: Collagen (Gly-Pro-Hydroxyproline repeat; Vit C needed for hydroxylation)

Mnemonic: "NAMANYA has 4 levels of Structure = Primary-Secondary-Tertiary-Quaternary = PSTQ"

---

PHENYLALANINE-TYROSINE METABOLISM

PHENYLALANINE
  │ [Phenylalanine hydroxylase (PAH)] + BH4 (tetrahydrobiopterin)
  ▼
TYROSINE
  │
  ├──→ [Tyrosine hydroxylase] → DOPA → Dopamine → NE → Epinephrine
  │                                    (CATECHOLAMINES - needs Vit C)
  │
  ├──→ [Tyrosinase] → Melanin (skin pigment)
  │                    ↓ deficiency = ALBINISM
  │
  ├──→ [Thyroid peroxidase] → Thyroid hormones (T3, T4)
  │
  └──→ Fumarylacetoacetate → Fumarate + Acetoacetate
       [Homogentisate oxidase]
              ↓ DEFICIENCY
         ALKAPTONURIA (accumulates homogentisate)

Clinical Disorders:

Mnemonic: "MANIK PKU = Phenylalanine → phenylPYRUVATE → Pee turns phenolic = MUSTY SMELL" "DIVYA's ALKAP turns black urine - homogentisate oxidase ki kami"

---

GLYCINE METABOLISM

• Synthesized from serine (reversible; PLP-dependent)
• Conjugated with bile acids → glycocholate, glycochenodeoxycholate
• Precursor: Heme (with succinyl-CoA), Purines, Creatine, Glutathione
• Inhibitory neurotransmitter (spinal cord)

Glycine Cleavage System:

Glycine → CO₂ + NH₃ + methylene-THF (one-carbon unit)
Requires: PLP, Lipoic acid, FAD, NAD⁺, THF
Deficiency → Non-ketotic hyperglycinemia

Clinical: Isoniazid (TB drug) inhibits PLP → deficient glycine/heme metabolism → peripheral neuropathy

---

SULFUR-CONTAINING AMINO ACID METABOLISM

Methionine Cycle:

METHIONINE + ATP
  ↓ [Met adenosyltransferase]
S-ADENOSYLMETHIONINE (SAM) ← Universal methyl donor
  ↓ [Methyltransferase]
S-Adenosylhomocysteine
  ↓
HOMOCYSTEINE ← Central metabolite
  │
  ├──[Methionine synthase + B12 + Folate]→ METHIONINE (recycled)
  │
  └──[Cystathionine β-synthase (CBS) + B6]→ Cystathionine → CYSTEINE

Homocystinuria:

Marfan vs Homocystinuria: Marfan = lens UP (superotemporal), AR dominant, normal intelligence Homocystinuria = lens DOWN (inferonasal), AR recessive, intellectual disability, thrombosis

Mnemonic: "SHUBHAM's HOMOCYST goes DOWN like his CBS enzyme" = Down-displaced lens

---

MAPLE SYRUP URINE DISEASE (MSUD)

• Defect: Branched-chain α-keto acid dehydrogenase (BCKD)
• Accumulates: Leucine, Isoleucine, Valine and their keto acids
• Features: Sweet maple syrup smell in urine, encephalopathy, cerebral edema, death if untreated
• Treatment: Low BCAA diet; thiamine (B1) supplementation (some responsive forms)
• Mnemonic: "RADHIKA's MAPLE = B1 ki zaroorat + BCAA restrict karo"

---

SECTION 6: NUCLEOTIDE METABOLISM

PURINE SALVAGE PATHWAY

HYPOXANTHINE + PRPP  →[HGPRT]→  IMP
GUANINE + PRPP       →[HGPRT]→  GMP
ADENINE + PRPP       →[APRT]→   AMP

PRPP = 5-Phosphoribosyl-1-pyrophosphate (the activated ribose donor)

HGPRT = Hypoxanthine-Guanine Phosphoribosyl Transferase APRT = Adenine Phosphoribosyl Transferase

---

SYNTHETIC NUCLEOTIDE ANALOGUES - Short Note

Mnemonic: "MANIK MAKES AMAZING ANTIMETABOLITES = MTX, 5-FU, 6-MP, AZT, Acyclovir"

---

CLINICAL: GOUT

↑ Uric acid (final product of purine catabolism in humans)
  ↓
Monosodium urate crystals deposit in joints
  ↓
Neutrophil phagocytosis → Inflammatory cascade
  ↓
Acute gout arthritis (podagra = great toe most common)

• ↑ Production: High purine diet, HGPRT deficiency (Lesch-Nyhan), G6PD def, psoriasis, myeloproliferative
• ↓ Excretion: Renal insufficiency, thiazides, low-dose aspirin, cyclosporine, alcohol

• Acute: Colchicine (inhibits microtubule polymerization → neutrophil migration blocked), NSAIDs, Corticosteroids
• Chronic: Allopurinol (xanthine oxidase inhibitor, structural analogue of hypoxanthine), Febuxostat, Uricosurics (Probenecid)

Crystal types:

• Gout = Needle-shaped, NEGATIVELY birefringent, yellow under parallel polarized light
• Pseudogout = Rhomboid, positively birefringent (calcium pyrophosphate)

Mnemonic: "NAMANYA's NEEDLE in toe = Negative birefringent = Gout"

---

LESCH-NYHAN SYNDROME

• Defect: HGPRT deficiency (X-linked recessive) → purines cannot be salvaged → ↑ uric acid
• Features: Gout + Self-mutilation (lip/finger biting - pathognomonic!) + Choreoathetosis + Intellectual disability + Spastic cerebral palsy
• Treatment: Allopurinol for uric acid; NO treatment for neurological features
• Mnemonic: "RADHIKA bites herself = HGPRT gone = Lesch-Nyhan"

---

OROTIC ACIDURIA

• Defect: UMP synthase (bifunctional: includes orotate phosphoribosyltransferase + orotidine decarboxylase)
• Features: Orotic acid in urine, megaloblastic anemia NOT responding to B12/folate, failure to thrive
• Treatment: Uridine supplementation (bypasses block)
• Distinguish from OTC deficiency: OTC def also has orotic aciduria BUT has hyperammonemia; orotic aciduria has NO hyperammonemia

Mnemonic: "DIVYA's OROTIC = No ammonia, Uridine treats it"

---

SEVERE COMBINED IMMUNODEFICIENCY (SCID)

• ADA deficiency: Adenosine deaminase deficiency → dATP accumulates → inhibits ribonucleotide reductase → ↓ dNTPs → lymphocyte death (T+B cell deficiency)
• PNP deficiency: Purine nucleoside phosphorylase → dGTP accumulates → mainly T-cell deficiency

Mnemonic: "SHUBHAM's ADA gone = dATP poisons lymphocytes = SCID"

---

SECTION 7: GENETICS

DNA REPLICATION (LAQ)

Key Enzymes:

Replication Steps:

1. ORIGIN of Replication (ORI) recognized by ORC (origin recognition complex)
2. Helicase → opens double helix → REPLICATION FORK
3. Primase → lays RNA primer
4. Leading strand: continuous synthesis 5'→3' toward fork
5. Lagging strand: discontinuous (Okazaki fragments, ~200 bp in eukaryotes)
6. DNA Pol I removes RNA primers, fills gaps
7. Ligase joins fragments
8. Telomerase extends 3' ends of chromosomes

Mnemonic: "MANIK's HAPPY TIP: Helicase, Primase, Topoisomerase for DNA Replication"

---

TRANSCRIPTION (LAQ)

Key Enzymes:

Post-Transcriptional Modifications (eukaryotes):

Pre-mRNA
  ↓ 5' 7-methylguanosine CAP added
  ↓ 3' Poly-A tail added (by poly-A polymerase, ~200 A's)
  ↓ SPLICING: Introns removed, Exons joined
     (spliceosome = snRNPs: U1,U2,U4,U5,U6)
  ↓
Mature mRNA → exported to cytoplasm

Functions:
- 5' Cap: Ribosome binding, protection from exonucleases
- Poly-A tail: mRNA stability, export, translation initiation
- Splicing: exon shuffling, alternative splicing → protein diversity

Mnemonic: "RADHIKA CAPS her mRNA = CAP + Poly-A + Splicing = 3 post-transcriptional mods"

---

PROTEIN BIOSYNTHESIS - TRANSLATION (LAQ)

Genetic Code Rules:

• Triplet, non-overlapping, universal (mostly), degenerate (multiple codons for 1 AA), unambiguous (1 codon = 1 AA only)
• Start codon: AUG (Met)
• Stop codons: UAA, UAG, UGA ("U Are Away", "U Are Gone", "U Go Away")

Components of Translation:

mRNA          - Template (read 5'→3')
tRNA          - Adapter (anticodon pairs with codon; carries AA)
               - Aminoacyl-tRNA synthetase charges tRNA (uses ATP)
               - Wobble position: 3rd base of codon can wobble
Ribosome      - 70S (prokaryote) = 30S + 50S
               - 80S (eukaryote) = 40S + 60S
               - A site: aminoacyl-tRNA entry
               - P site: peptidyl-tRNA (growing chain)
               - E site: exit (empty tRNA leaves)

Steps:

INITIATION:
  40S + mRNA + Met-tRNA + eIF → 80S complex at AUG

ELONGATION (cycle repeats):
  1. Aminoacyl-tRNA enters A site (EF-Tu + GTP in prokaryotes)
  2. Peptide bond formed (peptidyl transferase activity of 23S/28S rRNA)
  3. Translocation: ribosome moves 3' by 1 codon (EF-G + GTP)

TERMINATION:
  Stop codon (UAA/UAG/UGA) enters A site
  Release factors (RF1/2 in prokaryotes; eRF1 in eukaryotes) → polypeptide released

Post-Translational Modifications:

• Removal of signal peptide
• Glycosylation (N-linked in ER; O-linked in Golgi)
• Phosphorylation (Ser, Thr, Tyr - signaling)
• Hydroxylation (Pro, Lys in collagen - needs Vit C!)
• Acetylation (N-terminus)
• Ubiquitination (proteasomal degradation)

Mnemonic: "DIVYA GOES HAPPILY = N-Glycosylation in ER, O-glycosylation in Golgi"

---

REGULATION OF GENE EXPRESSION IN EUKARYOTES (Trending!)

Levels of Regulation:

1. EPIGENETIC
   - DNA methylation (CpG islands) → gene silencing
   - Histone acetylation → chromatin relaxation → gene activation
   - Histone methylation → chromatin condensation → gene silencing
   - MicroRNA (miRNA) → post-transcriptional silencing

2. TRANSCRIPTIONAL
   - Transcription factors bind enhancers/silencers
   - Enhancers can be thousands of bp away (looping!)
   - Mediator complex bridges TF and RNA Pol II
   - Steroid hormones → nuclear receptor → direct TF
   - Example: NF-κB, AP-1, p53 (tumor suppressor → activates repair genes)

3. POST-TRANSCRIPTIONAL
   - Alternative splicing (1 gene → multiple proteins; e.g., Dscam = 38,000 variants!)
   - RNA editing (ApoB: 4536 AA in liver; 2152 AA in intestine - C→U editing)
   - 5' cap and 3' Poly-A tail stability
   - miRNA/siRNA: binds 3'UTR of mRNA → degradation or translational block

4. TRANSLATIONAL
   - eIF-2 phosphorylation → global translation arrest (stress response)
   - Iron response element (IRE) - ferritin/transferrin receptor regulation

5. POST-TRANSLATIONAL
   - Phosphorylation, ubiquitination, proteolytic cleavage

Mnemonic: "SHUBHAM's EUKARYOTE = ETPPP = Epigenetic, Transcriptional, Post-transcriptional, Translational, Post-translational"

---

DNA REPAIR MECHANISMS (Trending!)

Mnemonic: "NAMANYA NEVER BRINGS HOME DAMAGED MATERIAL" NER=Never, BER=Brings, HR=Home, NHEJ=Damaged, MMR=Material

---

TELOMERES & TELOMERASE - Short Note

• Telomeres: Repetitive DNA sequences (TTAGGG repeats in humans) + protective proteins (Shelterin complex) at chromosome ends
• Problem: DNA polymerase cannot replicate very ends of chromosomes → end replication problem → chromosomes shorten with each division
• Solution: TELOMERASE - reverse transcriptase enzyme with its own RNA template (AAUCCC)
  • Extends 3' ends of chromosomes
  • Active in: Stem cells, germ cells, most cancer cells
  • Absent/low in: Somatic cells → aging, senescence

Cancer connection: Telomerase is REACTIVATED in 85-90% of human cancers → immortality Mnemonic: "MANIK's TTAGGG = Telomere keeps chromosome safe"

---

INHIBITORS OF PROTEIN SYNTHESIS (Short Note)

"30S inhibitors = SCAT" = Streptomycin, Chloramphenicol (actually 50S), Aminoglycosides, Tetracycline Better: "BIG MAC inhibits 50S" = B=Bleomycin, M=Macrolides, A=clindAmycin, C=Chloramphenicol, L=Linezolid

---

PCR (Polymerase Chain Reaction) - Short Note

STEP 1: DENATURATION (94-96°C) → Separate double-stranded DNA
STEP 2: ANNEALING (50-65°C) → Primers bind to target sequences
STEP 3: EXTENSION (72°C) → Taq polymerase extends from primers

After n cycles → 2ⁿ copies of target DNA
30 cycles → ~10⁹ copies

---

DNA FINGERPRINTING - Short Note

1. Extract DNA
2. PCR amplify STR loci (or RFLP analysis with restriction enzymes)
3. Gel electrophoresis → banding pattern
4. Southern blot / DNA profiling

---

RECOMBINANT DNA TECHNOLOGY - Short Note

KEY TOOLS:
1. Restriction endonucleases → cut DNA at specific sequences (sticky/blunt ends)
2. Ligase → join DNA fragments
3. Vectors (plasmids, bacteriophage, BAC) → carry foreign DNA
4. Host cells (E. coli, yeast) → express recombinant protein

STEPS:
Gene of interest → cut with RE → insert into vector → transform into host → 
select recombinants → culture → harvest recombinant protein

APPLICATIONS:
- Insulin production (recombinant human insulin)
- HBV vaccine (recombinant HBsAg)
- Erythropoietin (EPO)
- Tissue plasminogen activator (tPA)
- Growth hormone
- Southern blot (DNA), Northern blot (RNA), Western blot (protein)

Mnemonic: "RADHIKA's DNA KITCHEN: RE cuts, Ligase joins, Vector carries, Host cooks the protein"

---

SECTION 8: MISCELLANEOUS TOPICS

KIDNEY FUNCTION TESTS (KFT)

CKD Staging (GFR):

• Stage 1: ≥90 (kidney damage, normal GFR)
• Stage 2: 60-89 (mild)
• Stage 3: 30-59 (moderate) - uremia symptoms
• Stage 4: 15-29 (severe)
• Stage 5: <15 (ESRD - dialysis needed)

Mnemonic: "MANIK's CREATININE never lies about kidney"

---

LIVER FUNCTION TESTS (LFT)

ALT:AST ratio:

• ALT>AST = Viral hepatitis
• AST:ALT >2:1 = Alcoholic hepatitis Mnemonic: "RADHIKA: ALCOHOL = AST > ALT = A first (AST > ALT ratio)"

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THYROID FUNCTION TESTS (TFT)

Key biochemistry: T4 → T3 conversion: peripheral deiodinase (5'-deiodinase), inhibited by propylthiouracil (PTU) T3 is 3-4x more active than T4 Mnemonic: "TSH is BOSS - LOW TSH = hyperthyroid (boss is suppressed)"

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ACID-BASE BALANCE & DISORDERS

Henderson-Hasselbalch:

pH = 6.1 + log [HCO₃⁻] / (0.03 × PaCO₂)
Normal: pH 7.35-7.45, HCO₃⁻ 22-26 mEq/L, PaCO₂ 35-45 mmHg

Four Primary Disorders:

Anion Gap (AG):

AG = Na⁺ - (Cl⁻ + HCO₃⁻)     Normal = 8-12 mEq/L

HIGH AG metabolic acidosis (MUDPILES):
M - Methanol
U - Uremia (renal failure)
D - DKA (diabetic ketoacidosis)
P - Propylene glycol / Paraldehyde
I - Isoniazid / Iron
L - Lactic acidosis
E - Ethylene glycol
S - Salicylates

NORMAL AG (hyperchloremic) metabolic acidosis:
- Diarrhea (HCO₃⁻ loss)
- RTA (Renal Tubular Acidosis)
- Saline infusion

Mnemonic: "NAMANYA MUDPILES se acidotic ho gayi" = MUDPILES causes high AG metabolic acidosis

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BIOTRANSFORMATION (XENOBIOTICS)

Two Phases:

• Oxidation (most common): CYP450 system (NADPH, O₂ dependent)
  • CYP3A4 = metabolizes ~50% of drugs!
• Reduction, Hydrolysis
• Products may be MORE or LESS toxic

CYP450 Inducers: Rifampicin, Phenobarbital, Carbamazepine, St. John's Wort, Alcohol (chronic) → ↓ drug levels CYP450 Inhibitors: Ketoconazole, Erythromycin, Cimetidine, Grapefruit juice → ↑ drug toxicity Mnemonic: "RADHIKA PICKS" = Rifampicin, Phenobarb, Induces CYP450 = King's Speed up

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FREE RADICALS

Antioxidant Defense:

G6PD deficiency → ↓ NADPH → ↓ reduced glutathione → RBCs vulnerable to oxidative stress → hemolysis Mnemonic: "SHUBHAM's CAGE defense: CAtalase, Glutathione peroxidase, E-vitamin, SOD"

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CANCER BIOCHEMISTRY

Molecular Basis:

PROTO-ONCOGENES (normal growth promoters)
  ↓ mutation/amplification/translocation
ONCOGENES (constitutively active growth signals)

TUMOR SUPPRESSOR GENES (growth brakes)
  ↓ BOTH copies mutated (Knudson's two-hit hypothesis)
CANCER

Key Examples:

Mnemonic: "MANIK's CANCER = RAS MYC p53 = 3 most important oncogenes/suppressors"

Tumor Markers:

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HEMOGLOBIN, HEME SYNTHESIS, BILIRUBIN METABOLISM & JAUNDICE

HEME SYNTHESIS:

MITOCHONDRIA:
Succinyl-CoA + Glycine
  ↓ [ALA synthase] ← RATE-LIMITING STEP (needs PLP/B6)
  ↓ Inhibited by HEME (feedback inhibition)
δ-ALA (aminolevulinic acid)
  ↓ (to CYTOPLASM)

CYTOPLASM:
2 δ-ALA
  ↓ [ALA dehydratase] ← inhibited by LEAD (Pb)!
Porphobilinogen (PBG)
  ↓ [PBG deaminase] ← deficient in ACUTE INTERMITTENT PORPHYRIA (AIP)
Hydroxymethylbilane
  ↓ [Uroporphyrinogen III synthase]
Uroporphyrinogen III
  ↓ [Uroporphyrinogen decarboxylase] ← deficient in PORPHYRIA CUTANEA TARDA (PCT)
Coproporphyrinogen III
  ↓ (to MITOCHONDRIA)

MITOCHONDRIA:
Coproporphyrinogen III
  ↓
Protoporphyrinogen IX
  ↓ [Protoporphyrinogen oxidase]
Protoporphyrin IX
  ↓ [Ferrochelatase] ← inhibited by LEAD!
     + Fe²⁺
HEME

PORPHYRIAS (Exam Favourite!):

AIP mnemonic: "NAMANYA has AIP = 5 P's: Pain (abdomen), Psychological, Peripheral neuropathy, Port-wine urine, Precipitated by fasting/drugs"

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BILIRUBIN METABOLISM:

RBC lysis (after 120 days) in RES (spleen, liver)
  ↓
HEMOGLOBIN
  ↓ [Heme oxygenase] - breaks heme ring
BILIVERDIN + CO + Fe²⁺
  ↓ [Biliverdin reductase]
UNCONJUGATED BILIRUBIN (indirect)
= Water-INSOLUBLE, lipid-soluble, TOXIC (crosses BBB!)
= Transported in blood BOUND TO ALBUMIN
  ↓ → LIVER
  Taken up by hepatocytes (carrier-mediated)
  ↓ [UDP-Glucuronosyltransferase (UGT1A1)]
  + 2 UDP-Glucuronate
CONJUGATED BILIRUBIN (direct bilirubin) = Bilirubin diglucuronide
= Water-SOLUBLE, NON-toxic, excreted in BILE
  ↓ → Bile → Intestine
UROBILINOGEN (by gut bacteria)
  ↓
  ├── Excreted in STOOL as STERCOBILIN (brown color of stool)
  └── Reabsorbed, goes to kidney → UROBILIN (yellow color of urine)

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JAUNDICE - TYPES:

Mnemonic: "DIVYA's JAUNDICE types: Pre-hepatic = Pee pale + stool dark; Obstructive = Pee dark + stool pale"

Neonatal Jaundice:

• Physiological: UGT1A1 immature; peaks day 3-4; unconjugated; treated with phototherapy
• Pathological: Before day 1 (hemolytic), or direct hyperbilirubinemia
• Crigler-Najjar Type I: No UGT1A1 → fatal; exchange transfusion/phototherapy/liver transplant
• Crigler-Najjar Type II: ↓ UGT1A1 → phenobarb induces UGT → treatable
• Gilbert syndrome: Mild ↓ UGT1A1 (benign, stress/fasting precipitates); unconjugated; no treatment
• Dubin-Johnson: Defective conjugated bilirubin transport out of hepatocyte → direct; BLACK liver

Mnemonic: "SHUBHAM's CRIGLER can't CONJUGATE - Type I die, Type II survive with Phenobarb"

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QUICK-FIRE CLINICAL SUMMARY TABLE

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MASTER HINDI MNEMONIC TEAM

"MANIK, RISHIKA, NAMANYA, DIVYA, SHUBHAM, RADHIKA" - Each owns a subject!

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Sources: Lippincott's Illustrated Biochemistry 8th Ed; Basic Medical Biochemistry (Lieberman) 6th Ed; Harper's Illustrated Biochemistry 32nd Ed; Ganong's Review of Medical Physiology 26th Ed; Henry's Clinical Diagnosis by Laboratory Methods; Tietz Textbook of Laboratory Medicine 7th Ed

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