Amino Acid and Protein Metabolism: Transamination, Urea Cycle and Nitrogen Balance
What this domain tests
Amino acid and protein metabolism questions test transamination, ammonia handling, the urea cycle, and nitrogen balance.
Core rules
- Transamination transfers an alpha-amino group to an alpha-keto acid. Pyridoxal phosphate (vitamin B6) is the coenzyme. ALT and AST are clinically important transaminases.
- Oxidative deamination of glutamate by glutamate dehydrogenase releases free ammonia and NADH. Ammonia is toxic, so it is transported as alanine or glutamine and detoxified in the liver.
- The urea cycle occurs partly in liver mitochondria and partly in cytosol. Carbamoyl phosphate synthetase I is rate-limiting. Ornithine combines with carbamoyl phosphate to form citrulline; aspartate adds the second nitrogen; argininosuccinate splits to arginine and fumarate; arginase releases urea and ornithine.
- Urea synthesis consumes 3 ATP, but four high-energy phosphate bonds are used because argininosuccinate synthetase makes AMP + PPi.
- Positive nitrogen balance occurs in growth, pregnancy, and recovery; negative balance occurs in catabolism, starvation, and protein loss.
Worked example
In muscle, alanine transfers its amino group to alpha-ketoglutarate via ALT, forming pyruvate and glutamate. Glutamate can be oxidatively deaminated to alpha-ketoglutarate and ammonia. In the liver, ammonia enters carbamoyl phosphate synthetase I, and aspartate supplies the second nitrogen of urea. The carbon skeleton of alanine becomes pyruvate and can enter gluconeogenesis.
Traps
Transamination does not release free ammonia. Urea is not uric acid; uric acid is a purine end product. The urea cycle is not entirely cytosolic. Ammonia toxicity is not corrected by giving more protein; it requires treatment of the underlying liver failure and reduction of nitrogen load.