Enzymatic reductive amination of p-hydroxy- and phenylpyruvic acids as a method of synthesis of L-tyrosine and L-phenylalanine labelled with deuterium and tritium

A human inborn genetic disease, type I phenylketonuria [13] (PKU) is caused by a mutation in the gene encoding the enzyme phenylalanine dehydrogenase necessary to convert L-phenylalanine (L-Phe) to L-tyrosine, (L-Tyr). The accumulated L-Phe is metabolized by enforced side reaction to phenylpyruvate, phenylacetate, and phenyl-L-lactate excreted with urine, Fig. 1. The excess of phenylalanine hinders also the transport of other amino acids in the cell, causing a reduction in the synthesis of neurotransmitters (dopamine, norepinephrine and epinephrine) and melanins. Type I PKU non cured leads to mental retardation, brain damage, seizures, and skin discoloration. Type I tyrasinemia [10], the most severe form of tyrasinemia is inborn genetic disorder, in which L-Tyr cannot be effectively break down, is accompanied by elevated levels L-Tyr and its metabolites: p-hydroxyphenylpyruvate, p-hydroxyphenylacetate, and p-hydroxyphenyl-L-lactate in body fluids, Fig. 1. This disease is caused by a deficiency of enzyme fumarylacetoacetate hydrolase. The abnormal concentration of these metabolites inhibits the activity of other enzymes. This type I tyrasinemia causes liver, spleen, and kidney disturbances and mental retardation. Similarly, type II tyrosinemia is caused by a deficiency of the enzyme tyrosine aminotransferase. In this case the accumulation of L-Tyr causes the start of alternative path of its deEnzymatic reductive amination of p-hydroxyand phenylpyruvic acids as a method of synthesis of L-tyrosine and L-phenylalanine labelled with deuterium and tritium Katarzyna Pałka, Marianna Kańska