METABOLISM OF 3-HYDROXY- AND 3,4-DIHYDROXYPHENYLPYRUVIC ACIDS IN VIVO

¹ Aerospace Corporation, P.O. Box 95085, Los Angeles 45, California
² California Corporation for Biochemical Research, Los Angeles 63, California
³ Department of Physiological Chemistry, University of California School of Medicine, Los Angeles, California

In confirmation of the work of others L-3,4-dihydroxyphenylalanine (dopa) increases the blood pressure when injected intravenously, due to its decarboxylation to dopamine by dopa decarboxylase in vivo. This pressor response is prevented by prior injection of a dopa decarboxylase inhibitor, 5-(3-hydroxycinnamoyl) salicylic acid (HCS). The dopamine formed and excreted in the urine has been isolated and identified, and the amount formed is decreased by HCS.

m-Tyrosine also increases the blood pressure, due to the decarboxylated product m-tyramine, which was isolated from the urine. This decarboxylation also is blocked by HCS, as reflected by a decreased pressor response and excretion of m-tyramine. The chief metabolic products of m-tyrosine in the cat are m-hydroxyphenylacetic acid and m-hydroxyphenylaceturic acid.

m-Hydroxyphenylpyruvic and 3,4-dihydroxyphenylpyruvic acids increase the blood pressure of cats and rats when administered intravenously. It is shown that this is due to transaminiation to time corresponding amino acids, m-tyrosine and dopa, respectively, and their subsequent decarboxylation to m-tyramine and dopamine respectively. The m-tyrosine and m-tyramine have been isolated from the urine and identified.

HCS decreases the amount of m-tyramine formed from m-hydroxyphenylpyruvic acid.

m-Hydroxyphenylpyruvic acid administration in cats also leads to the urinary excretion of m-hydroxyphenylacetic acid and m-hydroxyphenyllactic acid.

Pyridoxine deficiency decreases kidney and liver dopa decarboxylase apoenzyme and coenzyme, with a greater effect on liver apoenzyme. This is reflected in a decreased blood pressure response to dopa and 3,4-dihydroxyphenylpyruvic acid.

p-Hydroxyphenylpyruvic acid, DL-phenylalanine and L-tyrosine have no pressor effects, and no urinary tyramine or phenylethylamine can be detected after the administration of the latter two compounds to cats and rats pretreated with iproniazid.