Chapter 37: Synthesis and Degradation of Amino Acids

The synthesis of nonessential amino acids relies on intermediates derived from central metabolic pathways, particularly glycolysis and the tricarboxylic acid cycle, with critical cofactors including pyridoxal phosphate functioning in transamination and deamination reactions, tetrahydrofolate mediating one-carbon transfer reactions, and tetrahydrobiopterin enabling hydroxylation reactions at aromatic rings. Serine, glycine, cysteine, and alanine are synthesized from glycolytic precursors, while glutamate, glutamine, proline, arginine, aspartate, and asparagine arise from TCA cycle intermediates, with tyrosine synthesized from the essential amino acid phenylalanine through hydroxylation. Amino acid degradation pathways classify amino acids as glucogenic when they yield substrates for gluconeogenesis such as pyruvate and oxaloacetate, or as ketogenic when they produce acetyl-coenzyme A or acetoacetate for ketone body formation, with certain amino acids like isoleucine and threonine functioning in both pathways. The chapter emphasizes clinically significant disorders arising from defects in amino acid metabolism, including phenylketonuria resulting from phenylalanine hydroxylase deficiency, homocystinuria caused by cystathionine beta-synthase deficiency leading to thrombosis and skeletal abnormalities, maple syrup urine disease from branched-chain alpha-keto acid dehydrogenase deficiency, alkaptonuria from homogentisate oxidase deficiency causing ochronosis, and tyrosinemias from defects in tyrosine catabolism. Primary oxaluria type one arises from glyoxylate transaminase deficiency, resulting in excessive oxalate accumulation and nephrolithiasis. The chapter integrates clinical case presentations demonstrating disease pathophysiology and therapeutic approaches including dietary restriction and cofactor supplementation, while highlighting nutritional relationships such as tryptophan's role in niacin synthesis and the metabolic consequences of vitamin B6 deficiency on transamination reactions.