The oxidation in liver of l-tyrosine to acetoacetate through p-hydroxyphenylpyruvate and homogentisic acid

Abstract

A series of enzymes in the soluble fraction of liver homogenates catalyses the oxidation of L-tyrosine to acetoacetate. One molecule of L-tyrosine is oxidized, with uptake of 4 atoms of O2 and the formation of one molecule of acetoacetate. Additions of alpha-ketoglutarate and catalytic amts. of ascorbic acid are required for the activity of the dialyzed enzyme. p-Hydroxyphenyl-pyruvate (I), 2,5-dihydroxyphenyl-pyruvate (II), and homogentisic acid (III) are also oxidized at comparable rates. I and III were identified as intermediates. I is formed by an L-tyrosine-glutamic acid transaminase. In the absence of the coenzyme, pyridoxal phosphate, this first step can be made to limit the rate of the overall reaction. I accumulates anaerobically, or, in the absence of ascorbic acid, aerobically. III is formed by the further oxidation of I, probably through II. The reaction requires catalytic amts. of ascorbic acid, III can be accumulated if the enzyme mixture is treated at pH 5 to destroy the system oxidizing it. Ascorbic and isoascorbic acids were equally effective in promoting the oxidation of I and could not be replaced by other compounds tested. The possibility that its action in tyrosine metabolism may be part of the vitamin activity of ascorbic acid is discussed.