🎯 NEET PG Biochemistry — High-Yield Topics

1. 🧬 Amino Acids & Proteins

• Essential amino acids — PVT TIM HaLL (Phe, Val, Thr, Trp, Ile, Met, His, Arg, Leu, Lys)
• Glucogenic only: Ala, Gly, Ser, Val, Pro, His, Arg, Asp, Glu, Cys, Met, Thr
• Ketogenic only: Leu, Lys
• Both: Ile, Phe, Trp, Tyr
• Charged amino acids at physiological pH: Asp, Glu (negative); Arg, Lys, His (positive)
• Collagen: Gly-X-Y structure; Gly is most abundant; Hydroxyproline & Hydroxylysine unique to collagen (require Vitamin C)
• Scurvy → defective hydroxylation → defective collagen

• Pepsin: active at pH 1–2 (only enzyme with acidic optimum in GIT)
• Trypsin: cleaves after Arg/Lys
• Chymotrypsin: cleaves after Phe/Trp/Tyr

2. 🧪 Enzymes (Very Heavily Tested)

• Km: measure of enzyme–substrate affinity (lower Km = higher affinity)
• Vmax: maximum velocity; reached when all enzyme active sites are saturated
• Competitive inhibition: Km↑, Vmax unchanged
• Non-competitive inhibition: Km unchanged, Vmax↓
• Allosteric enzymes: sigmoid kinetics, cooperativity, not Michaelis-Menten
• Isoenzymes of LDH: LDH-1 (heart), LDH-5 (liver/skeletal muscle) — classic PYQ
• Isoenzymes of CK: CK-MB (myocardial infarction marker)
• Proenzymes (zymogens): pepsinogen→pepsin, trypsinogen→trypsin, prothrombin→thrombin

3. 🍬 Carbohydrate Metabolism (Most Heavily Tested Topic)

Glycolysis

• Occurs in cytoplasm; net yield = 2 ATP (anaerobic), 8 ATP (aerobic)
• Rate-limiting enzyme: Phosphofructokinase-1 (PFK-1)
• Activated by: AMP, fructose-2,6-bisphosphate; Inhibited by: ATP, citrate
• Substrate-level phosphorylation steps: 1,3-BPG → 3-PG (PGK) and PEP → pyruvate (PK)

TCA Cycle

• Occurs in mitochondrial matrix
• Rate-limiting enzyme: Isocitrate dehydrogenase
• Net yield per acetyl-CoA: 3 NADH, 1 FADH2, 1 GTP
• Total ATP per glucose: 30–32 ATP

Gluconeogenesis

• Occurs in liver and kidney cortex
• Rate-limiting enzyme: Fructose-1,6-bisphosphatase
• Key substrates: Lactate (Cori cycle), Alanine (glucose-alanine cycle), Glycerol, Odd-chain fatty acids

HMP Shunt (Pentose Phosphate Pathway)

• Occurs in cytoplasm
• Produces NADPH (for reductive biosynthesis, RBC antioxidant defense) and ribose-5-phosphate
• Rate-limiting enzyme: Glucose-6-phosphate dehydrogenase (G6PD)
• G6PD deficiency → Heinz bodies, episodic hemolytic anemia with oxidant exposure

Glycogen Metabolism

• Glycogen synthase: key enzyme for synthesis
• Glycogen phosphorylase: key enzyme for breakdown
• von Gierke disease (Type I): G6P deficiency → ↑glycogen in liver + kidney, hypoglycemia, lactic acidosis
• McArdle disease (Type V): Muscle phosphorylase deficiency → painful cramps, no lactate rise after exercise
• Pompe disease (Type II): Lysosomal acid α-glucosidase deficiency → cardiomegaly, hypotonia

Galactose & Fructose

• Galactosemia: Galactose-1-phosphate uridylyltransferase deficiency → cataracts, liver disease, intellectual disability
• Essential fructosuria: Fructokinase deficiency — benign
• Hereditary fructose intolerance: Aldolase B deficiency — severe hypoglycemia

4. 🧴 Lipid Metabolism

• Fatty acid synthesis: Cytoplasm; requires NADPH; rate-limiting enzyme = Acetyl-CoA carboxylase
• Beta-oxidation: Mitochondria; produces NADH + FADH2 + acetyl-CoA
• Odd-chain FA oxidation: yields propionyl-CoA → succinyl-CoA (requires Vit B12)
• Ketone bodies: synthesized in liver, used by extrahepatic tissues; acetoacetate, β-hydroxybutyrate, acetone
• Ketoacidosis: liver cannot use ketone bodies (lacks thiophorase/succinyl-CoA transferase)
• Cholesterol synthesis: Liver cytoplasm/ER; rate-limiting enzyme = HMG-CoA reductase (inhibited by statins)
• Lipoproteins:
  • Chylomicrons: exogenous fat transport (intestine → periphery)
  • VLDL: endogenous fat from liver
  • LDL: cholesterol to peripheral tissues (atherogenic)
  • HDL: reverse cholesterol transport (protective)
• Abetalipoproteinemia: no chylomicrons/VLDL/LDL → fat malabsorption, acanthocytosis, ataxia

5. 🧠 Nitrogen Metabolism & Urea Cycle

• Urea cycle: partially mitochondria, partially cytoplasm
• Rate-limiting step: Carbamoyl phosphate synthetase I (CPS-I) — in mitochondria
• Activated by N-acetylglutamate
• Hyperammonemia → inhibits TCA cycle (α-KG depleted) → cerebral edema
• Treatment: Lactulose, sodium benzoate, sodium phenylacetate, dietary protein restriction

Amino acid disorders (classic PYQs):

6. 🧬 Molecular Biology & Genetics

• DNA replication: semiconservative; RNA primer required; 5'→3' synthesis
• DNA polymerase III (prokaryotes) = main replication enzyme
• Topoisomerase II (gyrase): relieves positive supercoiling ahead of fork (target of fluoroquinolones)
• Transcription: RNA polymerase I (rRNA), II (mRNA), III (tRNA, 5S rRNA)
• Mutations: missense, nonsense, frameshift, silent
• PCR: denaturation (94°C) → annealing (55°C) → extension (72°C)
• Southern blot: DNA; Northern blot: RNA; Western blot: protein; ELISA: antigen–antibody

Genetic disorders:

• Autosomal recessive: most inborn errors of metabolism
• Autosomal dominant: Familial hypercholesterolemia, Huntington's, NF1
• X-linked recessive: Hemophilia A & B, G6PD deficiency, Duchenne MD, Fabry disease

7. 💊 Vitamins (Heavily Tested)

8. 🔴 Heme Synthesis & Porphyrias

• Synthesis: starts and ends in mitochondria (middle steps in cytoplasm)
• Rate-limiting enzyme: ALA synthase (requires Pyridoxal phosphate/B6)
• Lead poisoning: inhibits ALA dehydratase and ferrochelatase → ↑ALA + ↑free erythrocyte protoporphyrin
• Acute Intermittent Porphyria (AIP): PBG deaminase deficiency → abdominal pain, psychiatric symptoms, neuropathy; urine turns dark on standing; NO skin involvement
• Porphyria Cutanea Tarda: Uroporphyrinogen decarboxylase deficiency → photosensitive blistering

9. ⚡ Bioenergetics & Electron Transport Chain

• ETC: Complex I (NADH dehydrogenase) → CoQ → Complex III → Cytochrome c → Complex IV (Cytochrome oxidase)
• P/O ratio: NADH → 2.5 ATP; FADH2 → 1.5 ATP
• Uncouplers (e.g., DNP, thermogenin in brown fat): ↑O2 consumption, ↓ATP production, ↑heat
• Inhibitors:
  • Complex I: Rotenone, metformin
  • Complex III: Antimycin A
  • Complex IV: CN⁻, CO
  • ATP synthase: Oligomycin

10. 🩸 Hemoglobin & Porphyrin

• Hemoglobin A: α2β2; HbF: α2γ2 (higher O2 affinity — left shift)
• Bohr effect: ↑CO2/↑H⁺ → right shift (O2 unloading to tissues)
• 2,3-BPG: right shift (↑in altitude, anemia)
• CO poisoning: left shift (cherry-red skin)
• Sickle cell: HbS (Glu→Val at position 6 of β chain); HbSS polymerizes when deoxygenated
• Thalassemia: α-thal (gene deletion), β-thal (point mutation)
• Methemoglobin: Fe³⁺; treated with methylene blue (requires G6PD)

✅ Quick Strategy for NEET PG Biochemistry

1. Prioritize: Carbohydrate metabolism > Enzymes > Vitamins > Molecular Biology > Lipid metabolism
2. Previous year questions: ~70% of questions repeat concepts from past 10 years
3. Glycogen storage diseases and amino acid disorders are standalone 1-mark gimmes — memorize the table
4. Enzyme deficiency → disease name is a very common question format
5. Lippincott's Illustrated Biochemistry is the gold-standard reference book for this subject
6. Focus on clinical correlates — NEET PG loves testing enzymes in the context of disease