Metabolism of Aromatic Amino Acids

Abstract

Phenylalanine and tyrosine are the simplest aromatic amino acids derived from alanine. Phenylalanine is an essential amino acid that our body cannot synthesise. This does not apply to tyrosine, which the body can synthesise only if there is a sufficient amount of phenylalanine – and availability of the enzyme participating in conversion of phenylalanine to tyrosine (Fig. 4.1). There is a close mutual relationship between phenylalanine and tyrosine; phenylalanine converts to tyrosine in the liver and to phenylpyruvic acid in the kidneys. Aromatic amino acids have a common intermediary metabolism, and conversion of phenylalanine to tyrosine and its further metabolism is controlled by a complicated enzymatic system. Disorder of the conversion of phenylalanine to tyrosine is called phenylketonuria, and it is one of the most frequently occurring recessive inherited diseases (approximately 1 patient per 10,000 newborns). In phenylketonuria, either the phenylalanine hydroxylase that converts phenylalanine to tyrosine (Fig. 4.1) or its cofactor tetrahydrobiopterin is absent (Blau et al. 2005; Crone et al. 2005). Treatment of children with phenylketonuria has to start in the 3rd month of life, because unrecognised phenylketonuria results in mental retardation, seizures, excessive tremor and hyperactivity. Phenylalanine has to be considerably reduced in food, and on the other hand tyrosine has to be added. Several types of hyperphenylalaninaemia that do not fulfill the criteria of the classical forms of phenylketonuria have been revealed during the examinations aimed at early diagnostics of phenylketonuria. In the case of the mild form of phenylketonuria, the body tolerates a higher intake of phenylalanine in food when compared to typical phenylketonuria. Tyrosine plasma concentration also increases. In cases of transient phenylketonuria, clinical and biochemical signs regress or completely vanish. In a special form of hyperphenylalaninaemia, without ketonuria, phenylalanine plasma concentration is slightly increased; however, phenylpyruvate is not excreted. After phenylalanine intake, its concentration increases; then it decreases, and tyrosine concentration can also increase. In both forms, decreased activity of phenylalanine hydroxylase to 10–20 % of normal values has been demonstrated. Disorders of phenylalanine metabolism are also present in Hartnup disease and generalised aminoaciduria. Approximately 90 % of phenylalanine in the body converts to tyrosine. The remaining 10 % of phenylalanine is used for protein synthesis. Tyrosine, which forms from phenylalanine under normal circumstances, can further be metabolised via various pathways with the formation of: