Amino acid catabolism is the process by which amino acids are broken down for energy or converted to metabolic intermediates. The nitrogen atoms removed from amino acids are toxic and must be converted to urea for excretion.
Amino Acid Catabolism
Transamination
The first step in amino acid degradation is the removal of the amino group. Aminotransferases transfer the amino group to alpha-ketoglutarate, forming glutamate and an alpha-keto acid corresponding to the original amino acid.
Oxidative Deamination
Glutamate is transported to the mitochondria, where glutamate dehydrogenase removes the amino group as free ammonia (NH4+), regenerating alpha-ketoglutarate. This reaction uses NAD+ or NADP+ as a cofactor.
Carbon Skeletons
The remaining carbon skeletons (alpha-keto acids) enter metabolic pathways. They are classified as glucogenic, ketogenic, or both. Glucogenic amino acids have carbon skeletons that can be converted to glucose via gluconeogenesis. Ketogenic amino acids have carbon skeletons that are converted to acetyl-CoA or acetoacetate, precursors for fatty acids or ketone bodies. Some amino acids are both glucogenic and ketogenic.
The Urea Cycle
Ammonia Transport
Free ammonia is toxic, especially to the brain. In most tissues, ammonia is converted to glutamine by glutamine synthetase for safe transport to the liver.
Urea Cycle Steps
The urea cycle occurs in the liver and converts ammonia into urea for excretion through a series of steps. In the mitochondria, ammonia combines with CO2 and ATP to form carbamoyl phosphate. Carbamoyl phosphate then combines with ornithine to form citrulline. Citrulline is transported to the cytoplasm, where it combines with aspartate to form argininosuccinate. Argininosuccinate is cleaved to arginine and fumarate. Finally, arginine is hydrolyzed by arginase to produce urea and regenerate ornithine, completing the cycle.
Net Result
The urea cycle converts two molecules of ammonia and one molecule of bicarbonate into one molecule of urea, which is excreted in urine. The fumarate produced links the urea cycle to the citric acid cycle.
