Biochemistry: Enzymes, Metabolism and Molecular Disease
Biochemistry: what is tested
Biochemistry tests enzyme kinetics, core metabolic pathways, vitamin cofactors, molecular biology and inborn errors. Questions often give a deficient enzyme and ask for the accumulated substrate, missing product or clinical pattern.
Core rules
- Michaelis-Menten kinetics: Km is the substrate concentration at half Vmax and reflects affinity (lower Km, higher affinity). Competitive inhibitors raise Km with unchanged Vmax; non-competitive inhibitors lower Vmax.
- Rate-limiting enzymes: phosphofructokinase-1 in glycolysis, citrate synthase and isocitrate dehydrogenase in the TCA cycle, cytochrome oxidase in oxidative phosphorylation.
- Cofactors: thiamine (TPP) for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase; riboflavin as FAD; niacin as NAD; pyridoxine for transamination; cobalamin and folate for one-carbon transfer.
- Glycogen storage disease type I is glucose-6-phosphatase deficiency; urea cycle defects cause hyperammonaemia; LDL receptor defects cause familial hypercholesterolaemia.
Worked example. An infant has fasting hypoglycaemia, lactic acidosis, hepatomegaly, hyperuricaemia and hyperlipidaemia; glucagon does not raise glucose. Reasoning: glucose-6-phosphatase deficiency (von Gierke disease) prevents release of glucose from liver glycogen and gluconeogenesis. Glucose-6-phosphate accumulates and is diverted to lactate and fat, while urate rises. In pyruvate dehydrogenase deficiency, lactate is also high but fasting hypoglycaemia is not the dominant pattern.
Traps that cost marks
- Confusing pyruvate carboxylase and pyruvate dehydrogenase defects.
- Forgetting that biotin is a cofactor for carboxylases.
- Attributing orotic aciduria to a urea cycle defect rather than to UMP synthase deficiency.
- Mixing up the rate-limiting enzymes of glycolysis and gluconeogenesis.