P-Hydroxyphenylpyruvic acid

Hydroxyphenylpyruvic acid has been prepared by alkaline hydrolysis of the azlactone of a-benzoylamino- -acetoxycin-namic acid 7 and by a two-step hydrolysis of the azlactone of a-acetamino- -acetoxycinnamic acid.8 p-Hydroxyphenylpyruvic acid has also been prepared by alkaline hydrolysis of 5-( -hy-droxybenzal)-3-phenylhydantoin.9 The procedure described here is adapted from published directions for the preparation of -hydroxyphenylpyruvic-3-C14 acid.5 5-( -Hydroxybenzal)hy-dantoin is prepared according to the method of Boyd and Robson.10... 

Prephenic acid has also been shown to be converted (by a partly purified enzyme preparation) to p-hydroxyphenylpyruvic acid. Diphosphop3rridine nucleotide was required for this reaction, suggesting oxidation of C4, followed by decarboxylation. This -prephenic dehydrogenase was missing in... 

Otherwise no immediate precursors of tyrosine appear to have been reported. Transamination of p-hydroxyphenylpyruvic acid has been suggested to be the final stage in yeasts (474), and may occur in E. coli (809), and isotopic evidence, discussed later, suggests that even if tyrosine is not formed from phenylalanine, the method of introduction of the tyrosine side chain is very similar to that postulated above for phenylalanine. Formation of p-hydroxyphenylpyruvic acid from prephenic acid can be readily visualized. 

Tyrosinosis and Other Cases of p-Hydroxyphenylpyruvic Acid Excretion... 

Early experiments by Bernheim, Felix, Sealock, and their co-workers on oxidation of tyrosine by liver breis showed an uptake of four atoms of oxygen per mole of tyrosine, with the production of one molecule each of carbon dioxide and acetoacetate, but no ammonia (60, 61, 261, 262, 789, 976). Felix and Zorn (261) found alanine to be formed and considered this to arise from a direct splitting of the tyrosine side chain. Although the experiments with man and intact animals already described made it seem very probable that p-hydroxyphenylpyruvic acid and homogentisic acid were normal intermediates in tyrosine metabolism, and although homogentisic acid was known to be readily metabolized by normal liver (e.g., 208, 695, 976) Felix and co-workers (262) considered p-hydroxyphenylpy-ruvic acid and homogentisic acid not to be intermediates in the breakdown of tyrosine by the liver system. 

Conversion of p-Hydroxyphenylpyruvic Acid to 2,5-Dihydroxyphenyl-pyruvic and Homogentisic Acids. Function of Ascorbic Acid and of Hematopoietic Factors... 

More detailed enzymic studies of the changes involved in the conversion of p-hydroxyphenylpyruvic acid to homogentisic acid have been made by two groups of workers, Williams and Sreenivasan (927-929) in rat liver preparations, and Uchida and co-workers (878) in rabbit liver preparations. Unfortunately the initial results of the two groups differ appreciably, but not all the conclusions are necessarily mutually exclusive. 

Uchida, Suzuki, and Ichihara (878) isolated a soluble enzyme system (thereby possibly excluding mitochondrial participation) from rabbit liver, and partially purified it. Two enzymes were involved. The first of these converted p-hydroxyphenylpyruvic acid to 2,5-dihydroxyphenylpyruvic acid. If this enzyme was resolved, vitamin C alone did not restore the activity, but vitamin C and vitamin B12 did. The amount of B12 required was very low, and they suggested that the true enzyme was a Bw derivative, possibly aquocobalamin hydroxide bound to enzyme protein, and that the function of the ascorbic acid was solely to stabilize the reactive form of the coenzyme. This agrees with the work of La Du and Greenberg (524), who considered the role of ascorbic acid to be quite unspecific. Ascorbate increased the rate of tyrosine oxidation in liver preparations but the net consumption was zero, and moreover numerous ene-diols were just as effective on a molar basis. La Du and Greenberg considered that ascorbic acid participates in a cyclic oxidation-reduction and happens to be a substance of the correct oxidation-reduction potential either to participate directly or to protect some other participant. 

The elevated 4-hydroxyphenyl acids are represented mainly by p-hydroxyphenyllactic and p-hydroxyphenylacetic acids due to its instability, p-hydroxyphenylpyruvic acid is less regularly found (B26). 

Z2. Zannoni, V. G., and La Du, B. N., Tyrosyluria resulting from inhibition of p-hydroxyphenylpyruvic acid oxidase in vitamin C-deficient guinea pigs. /. Biol. Chem. 236, 2667-2671 (1960). 

As added inactive tyrosine and p-hydroxyphenylpyruvic acid caused a greater dilution of activity in the protein than in the alkaloid being synthesized from [f/- C]fructose a separation of these two activities in L. williamsii into compartments was suggested. 

Biogenetic-type oxidation of p-hydroxyphenylpyruvic acid to homogentisic acid. < Photooxidation of p-hydroxyphenylpymvic acid (1) with Rose Bengal... 

The dye-sensitized photo-oxidation of phenols has been examined using CIDNP techniques.148 It is concluded from the observed polarizations of nuclear spin that sensitization by xanthene dyes (such as Rose Bengal) is the result of reversible hydrogen abstraction by the triplet dye molecule from the phenolic hydroxyl group. Any resulting photochemical reactions (e.g. with oxygen) arise from irreversible reactions of the phenoxy-radicals produced, rather than from direct reactions of the phenols with 102. Dye-sensitized photo-oxidation of p-hydroxyphenylpyruvic acid (94) in solution at pH 7 (conditions under which... 

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