SUMMARY

• 30.1 Nitrogen Removal Is the First Step in the Degradation of Amino Acids

  Surplus amino acids are used as metabolic fuel. The first step in their degradation is the removal of their α-amino groups by transamination to α-ketoacids. The α-amino group funnels into α-ketoglutarate to form glutamate, which is then oxidatively deaminated by glutamate dehydrogenase to give NH₄⁺ and α-ketoglutarate. NAD⁺ or NADP⁺ is the electron acceptor in this reaction.

• 30.2 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates

  The first step in the synthesis of urea is the formation of carbamoyl phosphate, which is synthesized from HCO₃⁻, NH₃, and two molecules of ATP by carbamoyl phosphate synthetase. Ornithine is then carbamoylated to citrulline by ornithine transcarbamoylase. These two reactions take place in mitochondria. Citrulline leaves the mitochondrion and condenses with aspartate to form argininosuccinate, which is cleaved into arginine and fumarate. The other nitrogen atom of urea comes from aspartate. Urea is formed by the hydrolysis of arginine, which also regenerates ornithine.

• 30.3 Carbon Atoms of Degraded Amino Acids Emerge As Major Metabolic Intermediates

  The carbon atoms of degraded amino acids are converted into pyruvate, acetyl CoA, acetoacetate, or an intermediate of the citric acid cycle. Most amino acids are solely glucogenic, two are solely ketogenic, and a few are both ketogenic and glucogenic. Alanine, serine, cysteine, glycine, threonine, and tryptophan are degraded to pyruvate. Asparagine and aspartate are converted into oxaloacetate. α-Ketoglutarate is the point of entry for glutamate and four amino acids (glutamine, histidine, proline, and arginine) that can be converted into glutamate. Succinyl CoA is the point of entry for some of the carbon atoms of three amino acids (methionine, isoleucine, and valine) that are degraded through the intermediate methylmalonyl CoA. Leucine is degraded to acetoacetate and acetyl CoA. The breakdown of valine and isoleucine is like that of leucine. Their α-ketoacid derivatives are oxidatively decarboxylated by the branched-chain α-ketoacid dehydrogenase.

  The rings of aromatic amino acids are degraded by oxygenases. Phenylalanine hydroxylase, a monooxygenase, uses tetrahydrobiopterin as the reductant. Four of the carbon atoms of phenylalanine and tyrosine are converted into fumarate, and four emerge in acetoacetate.

  Errors in amino acid metabolism were sources of some of the first insights into the correlation between pathology and biochemistry. Phenylketonuria results from the accumulation of high levels of phenylalanine in the body fluids. By unknown mechanisms, this accumulation leads to mental retardation unless the afflicted are placed on low-phenylalanine diets immediately after birth.