Synthesis and Degradation of Amino Acids and Amino Acid Derived Products

• Humans can synthesize only 11 of the 20 amino acids required for protein synthesis; the other 9 are considered essential amino acids for the diet.
• Amino acid metabolism to a large extent utilizes the cofactors pyridoxal phosphate, tetrahydrobiopterin, and tetrahydrofolate.
  • Pyridoxal phosphate is primarily required for transamination reactions.
  • Tetrahydrobiopterin is required for ring hydroxylation reactions.
  • Tetrahydrofolate is required for one-carbon metabolism (discussed further in Chapter 33).
• The nonessential amino acids can be synthesized from glycolytic intermediates (serine, glycine, cysteine and pyruvate), tricarboxylic acid cycle intermediates (aspartate, asparagine, glutamate, glutamine, proline, arginine, and ornithine), or from existing amino acids (tyrosine from phenylalanine).
• When amino acids are degraded, the nitrogen is converted to urea, and the carbon skeletons are classified as either glucogenic (a precursor of glucose) or ketogenic (a precursor of ketone bodies).
• Defects in amino acid degradation pathways can lead to disease.
  • Glycine degradation can lead to oxalate production, which may lead to one class of kidney stone formation.
  • Defects in methionine degradation can lead to hyper homocysteinemia, which has been linked to blood clotting disorders and heart disease.
  • A defect in branched-chain amino acid degradation leads to maple syrup urine disease, which has severe neurological consequences.
  • Defects in phenylalanine and tyrosine degradation lead to phenylketonuria, alcaptonuria, and albinism.
• Amino acids are also the precursors for the small nitrogen-containing neurotransmitters, such as the catecholamines, serotonin, and histamine.
• Glycine is required for the biosynthesis of heme. Mutations in enzymes involved in heme biosynthesis give rise to a class of diseases known as the porphyrias.