Biochemistry
Biochemistry questions target core metabolism, rate-limiting enzymes, vitamin deficiencies and inherited metabolic disease, usually presented as a short clinical vignette with an abnormal laboratory pattern.
Core pathways
- Rate-limiting enzymes worth memorising: phosphofructokinase-1 (glycolysis), fructose-1,6-bisphosphatase (gluconeogenesis), isocitrate dehydrogenase (TCA cycle), glucose-6-phosphate dehydrogenase (HMP shunt), carbamoyl phosphate synthetase I (urea cycle), ALA synthase (haem synthesis) and HMG-CoA reductase (cholesterol).
- Vitamins: thiamine deficiency causes beriberi and Wernicke encephalopathy; niacin deficiency causes pellagra; vitamin C deficiency causes scurvy; vitamin K deficiency prolongs the prothrombin time.
Inherited disease
- Glycogen storage disease type I (von Gierke): glucose-6-phosphatase deficiency with fasting hypoglycaemia, hepatomegaly, lactic acidosis, hyperuricaemia and hyperlipidaemia. Treated with frequent feeds and uncooked cornstarch.
- Lesch-Nyhan syndrome: HGPRT deficiency with hyperuricaemia, self-mutilation and choreoathetosis.
Worked example
A 9-month-old presents with irritability, sweating and hypoglycaemia after overnight fasting, plus a large liver and a lactate of 6 mmol/L. Ketones are low and urate is raised. Low ketones with lactic acidosis and hepatomegaly point to glucose-6-phosphatase deficiency rather than a fatty acid oxidation defect, which would produce hypoketotic hypoglycaemia without hepatomegaly.
Traps
Confusing vitamin B12 with folate deficiency, attributing Wernicke encephalopathy to alcohol alone rather than thiamine deficiency, and forgetting that pyruvate dehydrogenase deficiency is treated with a ketogenic diet.