MBBS Biochemistry – High-Yield Review Notes

Lipid Metabolism & Transport

  • Main post-absorptive lipid carrier ⇒ Chylomicrons

  • LDL-receptor ligand ⇒ Apo B-100

  • Essential fatty acid ⇒ Linoleic acid (ω-6); ω-3 = cardioprotective

  • Cholesterol → steroid hormones (aldosterone, testosterone, pregnenolone) & bile acids; NOT erythropoietin

  • HDL major apoprotein ⇒ Apo A-I; HDL mediates reverse cholesterol transport

  • β-oxidation: occurs in mitochondria; each cycle ↓ chain by 2 C, yields 1extFADH2+1extNADH+1extacetyl−CoA1 ext{ FADH}_2+1 ext{ NADH}+1 ext{acetyl-CoA}. Regulation by CPT-I (inhibited by malonyl-CoA)

  • Ketogenesis (liver mitochondria) ↑ in fasting, uncontrolled DM; regulated by insulin ↘, glucagon ↗

  • Statins inhibit HMG-CoA reductase (rate-limiting step of cholesterol synthesis)

  • Hyperlipidemia ➞ atherosclerosis via LDL oxidation, foam-cell formation

Alcohol & Xenobiotic Metabolism

  • Ethanol → Alcohol dehydrogenase → acetaldehyde → Aldehyde dehydrogenase → acetate

  • Phase I (Type I) xenobiotic reactions: oxidation, reduction, hydrolysis (main enzyme: CYP-450)

  • Phase II: conjugation (glucuronide, sulfate, methyl, acetyl, glycine, glutathione)

  • CYP-450 induces drug interactions; inhibited by cimetidine, grapefruit juice

Amino-Acid & Protein Facts

  • Lysine, Leucine = purely ketogenic

  • Mousy odour in PKU due to phenyl acetate; PKU: Phe ↗, Tyr ↘ → mental retardation, hypopigmentation

  • Histidine → Histamine by decarboxylation

  • Tryptophan → Melatonin, serotonin, niacin

  • SAM = universal methyl donor; SAH is product

  • Transamination requires PLP\text{PLP} (vit B$_6$)

  • Creatine synthesis: Gly + Arg (kidney) → Guanidinoacetate (liver) → Creatine (muscle); intestine not involved

  • Kwashiorkor: protein deficit with edema; Marasmus: total calorie lack, no edema

  • Anticodon (tRNA) – 3 nt, antiparallel to codon, first position exhibits wobble (G ↔ U, I pairs A/U/C)

  • Collagen: Gly-X-Y repeats, hydroxy-Pro/Lys need vit C; cross-link by lysyl oxidase (Cu2+^{2+})

Carbohydrate Pathways & Regulation

  • Glycolysis committed step ⇒ PFK-1 (fructose-6-P → fructose-1,6-BP); activated by AMP,F2,6BP\text{AMP}, F_{2,6}BP

  • Glucokinase: high K<em>mK<em>m, high V</em>maxV</em>{max}; active post-meal

  • HMP shunt (RBC): produces NADPHNADPH (for glutathione) + ribose-5-P

  • Von Gierke (G-6-phosphatase ↓), McArdle (muscle phosphorylase ↓), Pompe (acid maltase ↓)

  • Phototherapy in neonates ⇒ converts Z,EZ,E bilirubin to water-soluble isomers → ↑ excretion

Nucleic Acids & Molecular Biology

  • DNA replication: semi-conservative; origin → bidirectional forks; leading vs lagging (Okazaki) strands
    • Key enzymes: helicase, SSB, primase, DNA pol III/I, ligase, topoisomerase
    • Inhibitors: Ciprofloxacin (gyrase), Cytarabine, Actinomycin-D

  • PCR: denaturation 95 °C, annealing 50–65 °C, extension 72 °C (Taq polymerase); uses – diagnosis, cloning, forensics

  • Post-transcriptional modifications (hnRNA → mRNA): 5' cap, 3' poly-A, intron splicing (spliceosome)

  • Genetic code: triplet, non-overlapping, degenerate, unambiguous, universal (except mitochondria)

  • Wobble hypothesis: third codon base less stringent → fewer tRNAs needed

  • Telomerase (RNA-dependent DNA pol) adds TTAGGG\text{TTAGGG} repeats; declines with age

  • Restriction endonucleases cut palindromic DNA; basis of recombinant DNA technology

  • Vectors: plasmid, bacteriophage, retrovirus, liposome (not proteasome)

Vitamins & Minerals

  • Vit A: vision (11-cis-retinal → rhodopsin), epithelial integrity, antioxidant; deficiency → night-blindness, xerophthalmia

  • Vit D: active form 1,25-dihydroxycholecalciferol (Calcitriol); ↑ Ca2+^{2+} absorption, bone mineralization

  • Vit C: collagen synthesis, iron absorption, antioxidant; deficiency → scurvy, anemia

  • Vit B$_1$ (TPP) in oxidative decarboxylation (PDH, α-KG DH); deficiency in alcoholism (Wernicke)

  • Vit B$_9$/Folate: purine/pyrimidine synthesis; deficiency → megaloblastic anemia

  • Vit B$_{12}$: methylmalonyl-CoA → succinyl-CoA & homocysteine → methionine; deficiency → pernicious anemia, neuropathy

  • Minerals: Fe in heme, Zn in ALP, Se = antioxidant (GPx), I in thyroid hormones

Enzymes & Diagnostics

  • Isoenzymes: catalyse same reaction, differ in structure & tissue distribution (e.g., CK-MB for MI)

  • Plasma functional enzymes: clotting factors; plasma non-functional: ALP, ALT, AST

  • Obstructive jaundice ↑ ALP, GGT; Hepatocellular ↑ ALT > AST

  • Cardiac markers: Troponin T/I (best), CK-MB, LDH-1

  • Renal function: blood urea 20–4020–40 mg/dL, creatinine 0.6–1.20.6–1.2 mg/dL, microalbuminuria 30–30030–300 mg/day

  • HbA1c1c normal <5.6\%; diagnostic DM ≥ 6.5%6.5\%

Acid–Base & Electrolytes

  • Urea cycle (mitochondria + cytosol); rate-limiting CPS-I; NH$3$ + CO$2$ + ATP → carbamoyl-P
    • 2 N sources: NH$3$, aspartate. Brain detoxifies NH$3$ via glutamine synthetase

  • Acid–base: metabolic acidosis (anion-gap ↑ in renal failure, DKA, lactic acidosis); respiratory acidosis ↔ CO$_2$ retention

  • Buffers: bicarbonate pKa=6.1\mathrm{p}K_a=6.1 (major blood), phosphate, proteins, Hb

Hormones & Clinical Aspects

  • Steroid hormone mechanism: cytosolic receptor → nucleus, gene regulation

  • Peptide hormones use cAMP (except estrogen)

  • Thyroid tests: TSH, free T$3$/T$4$, anti-TPO Ab; primary hypothyroid = high TSH, low T$_4$

  • Diabetes insipidus: ↓ ADH or renal response; polyuria with low osmolar urine

Immunology Highlights

  • Antibody structure: 2 H + 2 L chains, disulfide bridges, Fab & Fc; IgG crosses placenta, IgM largest

  • MHC I presents endogenous Ag (all nucleated cells); MHC II exogenous (APC)

  • Monoclonal antibodies (e.g., rituximab) used therapeutically

Key Reference Ranges

  • Fasting glucose: 70–9970–99 mg/dL

  • Serum globulin: 2.5–3.52.5–3.5 g/dL (A:G ≈ 1.2–2.0)

  • ALP: 40–12040–120 U/L (↑ bone, liver, pregnancy)

  • Total bilirubin: <1 mg/dL (conj < 0.2)

  • Serum Na+^{+}: 135–145135–145 mEq/L

Molecular Techniques & Drugs

  • PCR, ELISA (Enzyme-Linked Immunosorbent Assay)

  • Southern (DNA), Northern (RNA), Western (protein) blotting

  • Methotrexate: inhibits DHFR\text{DHFR} → blocks THF → ↓ dTMP → anti-cancer

  • 5-Fluorouracil: inhibits thymidylate synthase

  • Nucleotide analogues (AZT, acyclovir) terminate viral DNA synthesis

(Use these concise bullets for rapid revision of MBBS Biochemistry-I & II essentials.)