Natural and synthetic inhibitors of UDP-glucuronosyltransferase.
Glucuronidation is a major detoxification pathway in vertebrates. The reaction is catalyzed by a family of UDP-glucuronosyltransferases (UGTs) and involves conjugation of many endobiotic and xenobiotic substances with glucuronic acid, forming inactive water-soluble glucuronides. UGT prevents the accumulation of potentially toxic compounds and/or their subsequent bioactivation to more toxic intermediates, although biologically active glucuronides are also known. Impairment of UGTs may have important toxicological consequences. Substances found to inhibit or down-regulate UGT activity include endogenous compounds, a wide range of clinically used drugs, environmental contaminants, and natural toxic substances present in the diet. The development of selective, active-site-directed UGT inhibitors greatly enables the study of various UGT isoenzymes. A promising approach offers the design of transition-state analogs of the glucuronidation reaction.
Grancharov
K
K
Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, BG-1113, Sofia, Bulgaria. kgran@obzor.bio21.bas.bg
Naydenova
Z
Z
Lozeva
S
S
Golovinsky
E
E
D000818:Animals; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D019216:Metals, Heavy / Q000494:pharmacology; D010575:Pesticides / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019216:Metals, Heavy; D010575:Pesticides; D015262:Xenobiotics; D014498:Uracil; D014453:Glucuronosyltransferase; D014529:Uridine