Conversion of tyrosine to phenolic derivatives by Taiwan cobra venom.
We have examined the ability of Taiwan cobra (Naja naja atra) venom to transform in vitro the amino acid tyrosine to phenolic oxidation products via 4-hydroxyphenylpyruvate. This amino acid can be released from neuropeptide substrates by oligopeptidases present in the venom. Using a variety of analytical techniques to probe a complicated series of reactions, we confirm that the L-amino acid oxidase present in the venom initially releases the keto form of 4-hydroxyphenylpyruvic acid and hydrogen peroxide after reacting with the tyrosine. Thereafter, there is evidence that a tautomerase in the venom promotes a partial conversion of the keto-form 4-hydroxyphenylpyruvic acid into an enol form. The enol is oxidised primarily to 4-hydroxybenzaldehyde and 4-hydroxyphenol (hydroquinone). The keto form is oxidised through to 4-hydroxyphenylacetic acid by the hydrogen peroxide co-released by the L-amino acid oxidase. The venom promotes both these spontaneous oxidation routes and also generates traces of other phenolics, some of which are as yet unidentified. We propose that reactions between the precursors of the major oxidation products may be responsible for generating unusual short-lived phenolics, possibly giving rise to special bioactivities that are relevant to venom action.
Nucaro
E
E
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK.
Jodra
M
M
Russell
E
E
Anderson
L
L
Dennison
P
P
Dufton
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001711:Biotransformation; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D004546:Elapid Venoms / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D009842:Oligopeptides / Q000378:metabolism; D010084:Oxidation-Reduction; D010667:Phenylpyruvic Acids / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D004546:Elapid Venoms; D009842:Oligopeptides; D010667:Phenylpyruvic Acids; C010590:4-hydroxyphenylpyruvic acid; C044757:tyrosyl-glycyl-glycine; D014443:Tyrosine; D002374:Catalase