Abnormal tyrosine and phenylalanine metabolism in patients with tyrosyluria and phenylketonuria; gas-liquid chromatographic analysis of urinary metabolites

Abstract

Gas-liquid chromatographic methods have been developed for the analysis of: urinary phenylalanine metabolites (I) in patients with phenylketonuria, tyrosine metabolites (II) in patients with a disturbed tyrosine metabolism at the level of p-hydroxyphenylpyruvate hydroxylase, and homogentisic acid in alkaptonuria.

Metabolites I include: phenylpyruvic, -lactic, -acetic (free and conjugated), -mandelic, o-hydroxyphenylacetic and benzoic (free and conjugated) acids. Metabolites II include: p-hydroxyphenylpyruvic, -lactic, -acetic and p-hydroxymandelic acids.

Urinary excretions of phenylalanine and its waste metabolites I in patients with phenylalanine hydroxylase deficiency, at high and moderate loads are given. In 3 patients with classical phenylketonuria the total excretion of phenylalanine and its waste metabolites were found to be 90, 81 and 82% of the phenylalanine intake. In 2 other patients, with a higher phenylalanine tolerance, 19 and 34% was found. The excretion intake ratio is proposed to be a better parameter for phenylalanine hydroxylation capacity than is plasma phenylalanine.

Urinary excretions of tyrosine and its waste metabolites in 2 patients with (inherited) liver disease and tyrosyluria were studied and compared with the urinary findings in a patient who presumably had a primary p-hydroxyphenylpyruvate hydroxylase deficiency. In one of the patients with liver disease the excretion/load ratio was determined. It is suggested that this ratio is a better clinical parameter than is plasma tyrosine.