Amino acid disorders

Abstract

Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Human utilize 21 different amino acids; most of these can be synthesized endogenously, but 9 are "essential" in that they must be ingested in the diet. In addition to their role as building blocks of protein, amino acids are key energy source (ketogenic, glucogenic or both), are building blocks of Kreb's (aka TCA) cycle intermediates and other metabolites, and recycled as needed. A metabolic defect in the metabolism of tyrosine (homogentisic acid oxidase deficiency) historically defined Archibald Garrod as key architect in linking biochemistry, genetics and medicine and creation of the term 'Inborn Error of Metabolism' (IEM). The key concept of a single gene defect leading to a single enzyme dysfunction, leading to "intoxication" with a precursor in the metabolic pathway was vital to linking genetics and metabolic disorders and developing screening and treatment approaches as described in other chapters in this issue. Amino acid disorders also led to the evolution of the field of metabolic nutrition and offending amino acid restricted formula and foods. This review will discuss the more common disorders caused by inborn errors in amino acid metabolism.

Keywords: Phenylketonuria (PKU); amino acids; dietary protein; intoxication; metabolic formula.

Figure 1

Overview of phenylalanine and tyrosine metabolism. Enzyme deficiencies are shown in the red star shapes. Green line represents mitochondrial membrane. SUAC, succinylacetone; BH4, tetrahydrobiopterin; HPA, hyperphenylalaninemia, PKU, phenylketonuria; TYR, tyrosinemia.

Figure 2

Overview of Branched-chain amino acid catabolism. Enzyme names are represented in italics and corresponding intra-mitochondrial enzyme deficiencies are shown in the red star shapes. Green line represents mitochondrial membrane. MSUD, maple syrup urine disease.

Figure 3

Overview of sulfated amino acid metabolism. Enzyme names are represented in italics and corresponding intra-mitochondrial enzyme deficiencies are shown in the red star shapes. Green line represents mitochondrial membrane. B12, vitamin B12; CBS, cystathionine beta synthase; HCY, Homocystinuria; MeCbl, methylcobalamin; MAT, methionine S-adenosyltransferase; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; SAHH, S-adenosylhomocysteine hydrolase; MTHFR, methylene tetrahydrofolate reductase; THF, tetrahydrofolate; SUOX, sulfite oxidase.