Biochemistry & Genetics

Molecular biology, metabolism, nutrition and classical genetics — the densest low-yield-feeling section that keeps showing up in vignettes.

Exam weight 10–13% · 2 QBank items · 3 flashcards

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Molecular biology

DNA replication is semiconservative; leading strand is continuous, lagging strand builds Okazaki fragments removed by DNA pol I (5'→3' exonuclease).
Nucleotide excision repair fixes bulky pyrimidine dimers — defective in xeroderma pigmentosum; mismatch repair defects cause Lynch syndrome.
RNA pol II makes mRNA and is inhibited by α-amanitin (death cap mushroom); pol I makes rRNA, pol III makes tRNA.
Splicing requires snRNPs; anti-Smith antibodies against snRNPs are specific for SLE.

Phosphofructokinase-1 is the rate-limiting step of glycolysis, activated by fructose-2,6-bisphosphate and AMP.
Pyruvate dehydrogenase needs 5 cofactors (thiamine, lipoic acid, CoA, FAD, NAD+); deficiency causes lactic acidosis and neurologic damage — treat with a ketogenic diet.
Arsenic inhibits lipoic acid: vomiting, rice-water stools, garlic breath.
Uncouplers (2,4-DNP, thermogenin, aspirin overdose) dissipate the proton gradient — oxygen use rises, ATP falls, temperature rises.

Von Gierke (G6Pase): severe fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia.
Pompe (acid maltase) 'trashes the pump' — cardiomegaly and early death; McArdle (myophosphorylase) gives exercise intolerance with a second-wind phenomenon and no rise in lactate.
Tay-Sachs: cherry-red macula, NO hepatosplenomegaly; Niemann-Pick: cherry-red macula WITH hepatosplenomegaly.
Fabry (X-linked, α-galactosidase A): angiokeratomas, neuropathic pain, renal failure — earliest and only X-linked one besides Hunter.

B1 thiamine deficiency: Wernicke-Korsakoff, wet and dry beriberi — always give thiamine before glucose in the malnourished.
B3 niacin deficiency: the 3 Ds — dermatitis, diarrhea, dementia; seen in Hartnup disease and carcinoid.
B12 vs folate: both give megaloblastic anemia, only B12 deficiency causes subacute combined degeneration and elevated methylmalonic acid.
Vitamin A excess: pseudotumor cerebri, teratogenicity; vitamin D excess: hypercalcemia, seen in sarcoidosis via 1α-hydroxylase in granulomas.

Hardy-Weinberg: p² + 2pq + q² = 1; carrier frequency for a rare autosomal recessive ≈ 2q.
Imprinting: Prader-Willi (paternal 15q11 deleted) — hyperphagia, obesity, hypogonadism; Angelman (maternal) — ataxia, inappropriate laughter, seizures.
Trinucleotide repeats: Huntington CAG (anticipation, caudate atrophy), fragile X CGG (macroorchidism, long face), Friedreich GAA.
Mitochondrial inheritance is maternal with heteroplasmy — variable severity across siblings (MELAS, Leber optic neuropathy).

PCR amplifies DNA; RT-PCR starts from RNA; qPCR quantifies transcript abundance.
Western blot detects protein (confirmatory in some infections), Southern DNA, Northern RNA.
Flow cytometry identifies cell-surface markers — used for leukemia immunophenotyping and CD4 counts.
CRISPR/Cas9 uses a guide RNA plus nuclease for targeted editing; knockout vs knock-in distinguishes loss vs gain of function models.