Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified a common nonpathological polymorphism of the human tyrosinase gene. In Caucasians codon 402 can be either CGA (arginine) [p = .85] or CAA (glutamine) [p = .15]. This polymorphism also occurs in American Blacks, but the codon 402CAA (Gln) allele was not detected in Oriental populations. The substitution of glutamine for arginine at codon 402 results in moderate thermoinstability of the corresponding tyrosinase polypeptide. Tyrosinase enzymatic activity expressed in HeLa cells transfected with a codon 402Gln tyrosinase cDNA is reduced by approximately 75 percent when cells are cultured at 37 degrees C as compared to 31 degrees C, whereas enzymatic activity of codon 402Arg tyrosinase is not temperature-sensitive. However, the genotype at codon 402 of tryosinase is not correlated with the apparent pigmentation phenotype in normal Caucasians.
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PMID:A polymorphism of the human tyrosinase gene is associated with temperature-sensitive enzymatic activity. 182 Feb 7

The antioxidant properties of the dietary dihydroxycinnamic acids [caffeic (CA), dihydrocaffeic (DHCA), and chlorogenic (CGA) acids] have been well studied but little is known about their metabolism. In this article, evidence is presented showing that CA, DHCA, and CGA form quinoids and hydroxylated products when oxidized by peroxidase/H(2)O(2) or tyrosinase/O(2). Mass spectrometry analyses of the metabolites formed with peroxidase/H(2)O(2)/glutathione (GSH) revealed that mono- and bi-glutathione conjugates were formed for all three compounds except CGA, which formed a bi-glutathione conjugate only when GSH was present. In contrast, the metabolism of the dihydroxycinnamic acids by tyrosinase/O(2)/GSH resulted in the formation of only mono-glutathione conjugates. In the absence of GSH, hydroxylated products and p-quinones of CA or CGA were formed by peroxidase/H(2)O(2). DHCA formed a hydroxylated adduct (even though GSH was present), as well as the corresponding p-quinone and dihydroesculetin, an intramolecular cyclization product. NADPH also supported rat liver microsomal-catalyzed CA-, CGA-, and DHCA-glutathione conjugate formation, which was prevented by benzylimidazole, a cytochrome P450 inhibitor. Furthermore, the cytotoxicity of CA, CGA, and DHCA toward isolated rat hepatocytes was markedly enhanced by hydrogen peroxide or cumene hydroperoxide-supported cytochrome P450 and was prevented by benzylimidazole. Cytotoxicity was also markedly enhanced by dicumarol, an NADPH/oxidoreductase inhibitor. These results suggest that dihydroxycinnamic acids were metabolically activated by P450 peroxidase activity to form cytotoxic quinoid metabolites.
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PMID:Caffeic acid, chlorogenic acid, and dihydrocaffeic acid metabolism: glutathione conjugate formation. 1160 18

Chlorogenic acid is the major diphenol of many fruits, where it is oxidized enzymatically by polyphenol oxidase (PPO) or peroxidase (POD) to its o-quinone. In spectrophotometric studies of chlorogenic acid oxidation with a periodate ratio of [CGA]0/[IO4-]0 < 1 and [CGA]0/[IO4-]0 > 1, the o-quinone was characterized as follows: lambda(max) at 400 nm and epsilon = 2000 and 2200 M-1 cm-1 at pH 4.5 and 7.0, respectively. In studies of o-quinone generated by the oxidation of chlorogenic acid using a periodate at ratio of [CGA]0/[IO4-]0 > 1, a reaction with the remaining substrate was detected, showing rate constants of k = 2.73 +/- 0.17 M-1 s-1 and k' = 0.05 +/- 0.01 M-1 s-1 at the above pH values. A chronometric spectrophotometric method is proposed to kinetically characterize the action of the PPO or POD on the basis of measuring the time it takes for a given amount of ascorbic acid to be consumed in the reaction with the o-quinone. The kinetic constants of mushroom PPO and horseradish POD are determined.
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PMID:Kinetic characterization of the oxidation of chlorogenic acid by polyphenol oxidase and peroxidase. Characteristics of the o-quinone. 1726 94