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📚 MBBS Biochemistry - High-Yield Revision Notes

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1. ENZYMOLOGY

Key Concepts

• Biological catalysts (mostly proteins; ribozymes are RNA enzymes)
• Lower the activation energy of a reaction
• Not consumed in the reaction; highly specific (substrate specificity)

Enzyme Kinetics (Michaelis-Menten)

• Lineweaver-Burk plot = double reciprocal (1/V vs 1/[S]); x-intercept = -1/Km, y-intercept = 1/Vmax

Enzyme Inhibition

MBBS tip: Competitive inhibitors compete with substrate for the active site; can be overcome by increasing substrate concentration. Non-competitive bind allosteric sites.

Regulation of Enzyme Activity

1. Allosteric regulation - effector binds non-active site; sigmoidal kinetics (not Michaelis-Menten)
2. Covalent modification - phosphorylation (kinases) / dephosphorylation (phosphatases)
3. Zymogen activation - inactive precursors (e.g. trypsinogen → trypsin, pepsinogen → pepsin)
4. Feedback inhibition - end product inhibits an early enzyme in the pathway

Isoenzymes (High-yield for MBBS)

Cofactors & Coenzymes

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2. MOLECULAR BIOLOGY

DNA Structure

• Double helix; antiparallel strands; base pairing: A=T (2 H-bonds), G≡C (3 H-bonds)
• B-DNA is physiological form; right-handed helix, 10 bp per turn
• Chargaff's rule: %A = %T; %G = %C

DNA Replication

• Semi-conservative (each new DNA has one old + one new strand)
• Occurs in S phase of cell cycle
• Origin of replication - starts at AUG (multiple in eukaryotes, one in prokaryotes)

• Leading strand - continuous synthesis (5'→3')
• Lagging strand - discontinuous Okazaki fragments

Transcription (DNA → RNA)

• RNA Polymerase II - makes mRNA in eukaryotes
• Prokaryote RNA Pol - one enzyme for all RNA types
• Promoter - TATA box (eukaryotes), Pribnow box (prokaryotes)
• mRNA Processing (eukaryotes): 5' cap (7-methylguanosine) + poly-A tail + splicing of introns

Introns = "In the trash" (removed); Exons = "Expressed"

Translation (mRNA → Protein)

• Occurs on ribosomes: 80S (60S + 40S) eukaryotes; 70S (50S + 30S) prokaryotes
• Codons on mRNA; Anticodons on tRNA
• Start codon: AUG (methionine); Stop codons: UAA, UAG, UGA ("U Are Away", "U Are Gone", "U Go Away")
• Stages: Initiation → Elongation → Termination

Mutations

DNA Repair

• Nucleotide excision repair - fixes bulky adducts (UV damage, xeroderma pigmentosum)
• Base excision repair - fixes small base damage (deamination)
• Mismatch repair - corrects replication errors (defect → HNPCC/Lynch syndrome)
• Double-strand break - homologous recombination (accurate) or NHEJ (error-prone)

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3. CELLS

Cell Organelles & Functions

Cytoskeleton Components

Cilia - 9+2 arrangement of microtubules; dynein = motor protein. Dynein defect → Kartagener syndrome

Cell Membrane

• Fluid mosaic model: phospholipid bilayer with embedded proteins
• Hydrophilic heads face outward; hydrophobic tails face inward
• Cholesterol - stabilizes membrane fluidity
• Glycoproteins/glycolipids - cell recognition, blood group antigens

Cell Cycle

G1 → S (DNA synthesis) → G2 → M (Mitosis)
         ↑ Cyclin-CDK checkpoints

• G1/S checkpoint - regulated by cyclin D/CDK4,6 → phosphorylates Rb → releases E2F
• G2/M checkpoint - cyclin B/CDK1
• p53 - "guardian of the genome"; activates p21 (CDK inhibitor) → cell cycle arrest
• Rb gene - tumor suppressor; mutation → retinoblastoma, osteosarcoma

Cell Signaling (important types)

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4. CARBOHYDRATES

Glycolysis (Cytoplasm)

• Glucose (6C) → 2 Pyruvate (3C)
• Net yield: 2 ATP + 2 NADH (anaerobic: 2 lactate)
• Key regulatory enzymes:
  1. Hexokinase/Glucokinase - step 1 (Glucokinase in liver: high Km, induced by insulin)
  2. Phosphofructokinase-1 (PFK-1) - rate-limiting step; inhibited by ATP, citrate; activated by AMP, fructose-2,6-bisphosphate
  3. Pyruvate kinase - final step

Pyruvate Dehydrogenase Complex (PDC)

• Pyruvate → Acetyl-CoA (irreversible, in mitochondria)
• Requires: B1 (TPP), B2 (FAD), B3 (NAD+), B5 (CoA), Lipoic acid
• Mnemonic: "Tender Loving Care For Nerves" (TPP, Lipoate, CoA, FAD, NAD+)
• PDC deficiency → lactic acidosis, neurological problems

TCA Cycle (Krebs Cycle) - Mitochondria

• Acetyl-CoA (2C) + OAA (4C) → Citrate (6C) → ... → OAA
• Yield per turn: 3 NADH + 1 FADH2 + 1 GTP + 2 CO2
• Rate-limiting enzyme: Isocitrate dehydrogenase
• Key enzymes: Citrate synthase, Isocitrate DH, α-KG DH, Succinate DH (only membrane-bound; FADH2)

Electron Transport Chain (ETC) + Oxidative Phosphorylation

• Located in inner mitochondrial membrane
• Complex I (NADH → CoQ), II (FADH2 → CoQ), III (CoQ → Cyt c), IV (Cyt c → O2)
• ATP synthase (Complex V) - uses proton gradient (chemiosmosis)
• Yield: NADH = 2.5 ATP; FADH2 = 1.5 ATP
• Total glucose oxidation: ~30-32 ATP

Gluconeogenesis

• Glucose synthesis from non-carbohydrate precursors (lactate, glycerol, amino acids - especially alanine)
• Primarily in liver (also kidney in fasting)
• Bypasses 3 irreversible glycolysis steps using:
  1. Pyruvate carboxylase → OAA (requires biotin)
  2. PEPCK → PEP
  3. Fructose-1,6-bisphosphatase
  4. Glucose-6-phosphatase (liver only)

Glycogen Metabolism

HMP Shunt (Pentose Phosphate Pathway)

• In cytoplasm; no ATP production
• Products: NADPH (for anabolic reactions and oxidative burst), Ribose-5-phosphate (nucleotide synthesis)
• Rate-limiting: Glucose-6-phosphate dehydrogenase (G6PD)
• G6PD deficiency → hemolytic anemia with oxidant stress (primaquine, fava beans)

Blood Glucose Regulation

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5. AMINO ACIDS & METABOLISM

Essential Amino Acids (10)

"PVT TIM HaLL" - Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine (conditionally), Leucine, Lysine

Amino Acid Structure

• All have: α-amino group, α-carboxyl group, H, and R (side chain)
• Amphoteric - act as acid and base (zwitterion at physiological pH)
• At pI (isoelectric point): net charge = 0

Transamination

• Transfer of amino group from amino acid to α-ketoacid
• Key enzyme: Aminotransferases (require PLP/B6)
• ALT (alanine transaminase) - liver-specific
• AST (aspartate transaminase) - liver + heart

Urea Cycle (liver mitochondria + cytoplasm)

• Activated by N-acetylglutamate (NAG)
• NAG synthesis activated by arginine

Key Amino Acid Disorders

One-Carbon Metabolism

• Folate (THF) + B12 carry one-carbon units
• Methionine synthase: Homocysteine + CH3-THF → Methionine + THF (needs B12)
• Folate deficiency → megaloblastic anemia, neural tube defects
• B12 deficiency → megaloblastic anemia + subacute combined degeneration of spinal cord
• Methylmalonic acid ↑ in B12 deficiency only (distinguishes from folate deficiency)

Heme Synthesis & Porphyrias

• ALA synthase (rate-limiting; mitochondria) - requires B6
• Porphobilinogen → Uroporphyrinogen → Coproporphyrinogen → Heme

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6. LIPIDS

Fatty Acid Synthesis (Cytoplasm)

• Glucose → Acetyl-CoA → Malonyl-CoA → Palmitate (16C)
• Rate-limiting enzyme: Acetyl-CoA Carboxylase (ACC); requires biotin
• Activated by insulin and citrate; inhibited by glucagon, epinephrine, palmitoyl-CoA
• Fatty acid synthase (FAS) is a multifunctional enzyme

Beta-Oxidation (Mitochondria)

• Breaks down fatty acids → Acetyl-CoA
• Entry requires carnitine shuttle (long-chain FA cannot enter directly)
  • Carnitine palmitoyltransferase I (CPT-I) - rate-limiting; inhibited by malonyl-CoA
• Each cycle removes 2 carbons as Acetyl-CoA
• Yield per cycle: 1 NADH + 1 FADH2 + 1 Acetyl-CoA

Ketone Bodies

• Produced in liver mitochondria during prolonged fasting, starvation, DKA
• Acetoacetate, β-hydroxybutyrate, acetone
• Cannot be used by liver (lacks thiophorase/succinyl-CoA acetoacetyl transferase)
• Used by brain, heart, skeletal muscle, kidney cortex

In DKA: ketones ↑, metabolic acidosis, fruity breath (acetone)

Cholesterol Metabolism

• Synthesized in liver from Acetyl-CoA (cytoplasm)
• Rate-limiting enzyme: HMG-CoA reductase (target of statins)
• Cholesterol → bile acids (bile salt synthesis), steroid hormones, Vitamin D, cell membranes

Lipoproteins

• ApoC-II - activates lipoprotein lipase (LPL)
• ApoE - receptor binding; ApoE4 → ↑ Alzheimer's risk
• ApoB-100 - LDL receptor binding

Phospholipids & Sphingolipids

Sphingolipidoses

Mnemonic for Tay-Sachs vs Niemann-Pick: Tay-Sachs = No Spleen; Niemann-Pick = Pick up the spleen

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Quick-Reference: High-Yield MBBS Biochemistry Facts

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1. Enzyme kinetics graphs (Lineweaver-Burk)
2. Glycogen storage diseases and sphingolipidoses (frequently asked as clinical vignettes)
3. Urea cycle enzyme defects and distinguishing features
4. Vitamin-coenzyme pairings and their deficiency diseases
5. Isoenzymes in disease (LDH, CK, ALP)