Monitoring Phenylalanine—Tyrosine Metabolism by High-Resolution Liquid Chromatography of Urine

Abstract

Abstract Urines, selected to demonstrate the utility of the LC system known as the "UV-Analyzer" for simultaneous investigation of a wide range of metabolites, were obtained from Parkinsonian patients being treated with l-DOPA alone or l-DOPA plus α-methyldopahydrazine, a dopa decarboxylase inhibitor. Sulfate conjugates are the major excretion products of those metabolites of l-DOPA retaining the catechol (3,4-dihydroxyphenyl) structure. Administration of the dopa decarboxylase inhibitor considerably decreased urinary excretion of 3,4-dihydroxyphenylacetic and 3,4-dihydroxymandelic acids and increased excretion of 3-methoxy-4-hydroxy-phenyl lactic acid. Urinary chromatograms obtained for several children with neurological disorders manifest by seizures, infantile autism, and mental retardation showed elevated excretion of 4-hydroxyphenylacetic (a metabolite of tyramine) and 4-hydroxyhippuric acids. Two of the more severely affected children excreted a new metabolite, identified by mass spectrometry and gas chromatography—mass spectrometry as α-methoxy-α-(3-methoxy-4-hydroxyphenyl)-acetic acid. This homolog of 3-methoxy-4-hydroxymandelic acid (VMA) was observed also in urine samples from patients with other types of diseases, including chronic lymphocytic leukemia, Lesch— Nyhan syndrome, malignant carcinoid, synovial sarcoma, multiple myeloma, and embryonic neoplasia. Its metabolic precursors are unknown.