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

The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational leukoderma. RK has a structure closely related to 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause leukoderma in the skin of consumers in 2013. Rhododendrol is a good substrate for tyrosinase and causes a tyrosinase-dependent cytotoxicity to melanocytes, cells that are responsible for skin pigmentation. Therefore, it is expected that RK exerts its cytotoxicity to melanocytes through the tyrosinase-catalyzed oxidation to cytotoxic o-quinones. The results of this study demonstrate that the oxidation of RK by mushroom tyrosinase rapidly produces 4-(3-oxobutyl)-1,2-benzoquinone (RK-quinone), which is converted within 10-20 min to (E)-4-(3-oxo-1-butenyl)-1,2-benzoquinone (DBL-quinone). These quinones were identified as their corresponding catechols after reduction by ascorbic acid. RK-quinone and DBL-quinone quantitatively bind to the small thiol N-acetyl-l-cysteine to form thiol adducts and can also bind to the thiol protein bovine serum albumin through its cysteinyl residue. DBL-quinone is more reactive than RK-quinone, as judged by their half-lives (6.2 min vs 10.5 min, respectively), and decays rapidly to form an oligomeric pigment (RK-oligomer). The RK-oligomer can oxidize GSH to GSSG with a concomitant production of hydrogen peroxide, indicating its pro-oxidant activity, similar to that of the RD-oligomer. These results suggest that RK is cytotoxic to melanocytes through the binding of RK-derived quinones to thiol proteins and the pro-oxidant activity of the RK-oligomer.
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PMID:Tyrosinase-Catalyzed Oxidation of the Leukoderma-Inducing Agent Raspberry Ketone Produces (E)-4-(3-Oxo-1-butenyl)-1,2-benzoquinone: Implications for Melanocyte Toxicity. 2821 12

The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational leukoderma. RK is a carbonyl derivative of 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause leukoderma in skin of many consumers. These two phenolic compounds are oxidized by tyrosinase and the resultant products seem to cause cytotoxicity to melanocytes by producing reactive oxygen species and depleting cellular thiols through o-quinone oxidation products. Therefore, it is important to understand the biochemical mechanism of the oxidative transformation of these compounds. Earlier studies indicate that RK is initially oxidized to RK quinone by tyrosinase and subsequently converted to a side chain desaturated catechol called 3,4-dihydroxybenzalacetone (DBL catechol). In the present study, we report the oxidation chemistry of DBL catechol. Using UV-visible spectroscopic studies and liquid chromatography mass spectrometry, we have examined the reaction of DBL catechol with tyrosinase and sodium periodate. Our results indicate that DBL quinone formed in the reaction is extremely reactive and undergoes facile dimerization and trimerization reactions to produce multiple isomeric products by novel ionic Diels-Alder type condensation reactions. The production of a wide variety of complex quinonoid products from such reactions would be potentially more toxic to cells by causing not only oxidative stress, but also melanotoxicity through exhibiting reactions with cellular macromolecules and thiols.
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PMID:Oxidative Oligomerization of DBL Catechol, a potential Cytotoxic Compound for Melanocytes, Reveals the Occurrence of Novel Ionic Diels-Alder Type Additions. 3294 64