General Principles of Foundational Science
Core biochemistry and molecular biology
Enzyme kinetics: Km is the substrate concentration at half-maximal velocity and varies inversely with affinity; Vmax reflects enzyme amount. Competitive inhibitors raise Km with unchanged Vmax; noncompetitive inhibitors lower Vmax; mixed inhibitors alter both. Rate-limiting enzymes to know: PFK-1 (glycolysis), isocitrate dehydrogenase (TCA), carbamoyl phosphate synthetase I (urea cycle), HMG-CoA reductase (cholesterol). Know ATP yields per glucose and which tissues are insulin-independent (brain via GLUT3, RBC via GLUT1, liver via GLUT2/glucokinase).
Genetics: separate oncogenes (gain of function, one allele sufficient: RAS, MYC, HER2) from tumor suppressors (loss of function, both alleles: RB, TP53, APC, VHL). Review trinucleotide repeats, imprinting (Prader vs Angelman), mitochondrial inheritance, and Hardy-Weinberg assumptions.
Pharmacology: most drugs follow first-order kinetics; zero-order (saturable) for phenytoin, ethanol, and high-dose aspirin. Vd = dose divided by plasma concentration; a large Vd implies tissue sequestration and poor dialyzability. Autonomic receptors are high yield: alpha-1 (vasoconstriction), beta-1 (rate/contractility), beta-2 (bronchodilation, tocolysis), muscarinic (secretions, bradycardia).
Traps
Potency versus efficacy; confusing a Km change with a Vmax change; PPV versus sensitivity (PPV depends on prevalence, sensitivity does not); type I versus type II error; confounding versus effect modification; assuming a low-yield lab value means low-yield reasoning.
Worked rule
On a Lineweaver-Burk plot, a competitive inhibitor shifts the x-intercept rightward (higher Km) with an unchanged y-intercept (same Vmax); a noncompetitive inhibitor shifts the y-intercept upward (lower Vmax) with an unchanged x-intercept.