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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)