The UDP-glucuronosyltransferase (UGT) enzyme 'superfamily' contributes to the metabolism of a myriad of drugs, nondrug xenobiotic agents, and endogenous compounds. Although the individual UGT isoforms exhibit distinct but overlapping substrate selectivities, structural features of substrates that confer selectivity remain largely unknown. Using methods developed for pharmacophore fingerprinting...

Individuals with type 2 diabetes display metabolic abnormalities, such as hyperglycemia, increased free fatty acids, insulin resistance, and altered ceramide levels, that contribute to vascular dysfunctions and compromised oxygen delivery. Caenorhabditis elegans fed a glucose-supplemented diet or with altered ceramide metabolism, due to a hyl-2 mutation, are sensitive to oxygen deprivation (ano...

Significant evidence exists regarding altered CYP450 enzymes in chronic renal insufficiency (CRI), although none exists for the phase II enzymes. The objective of this study was to investigate the effect of CRI on hepatic and renal UDP-glucuronyltransferase (UGT) enzymes. Three groups of rats were included: CRI induced by the 5/6th nephrectomy model, control, and control pair-fed (CPF) rats. UG...

The human UDP-glycosyltransferase (UGT) gene superfamily generates 22 canonical transcripts coding for functional enzymes and also produces nearly 150 variant UGT through alternative splicing intergenic splicing. In the present study, our analysis of circRNA databases identified backsplicing events that predicted 85 circRNAs from UGT genes, with 33, 11, 19 UGT1A, UGT2B4<...

Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Environmental and dietary factors have crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a superfamily of enzymes essential for the detoxification of carcinogens, may alter enzyme activity and subsequently may play a role in EC etiology. Rather than solel...

UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation and elimination of putative tobacco carcinogens such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosarnino)-l-(3-pyridyl)-l-butanone (NNK), which may reduce competing bioactivation and toxicity. B[a]P-initiated cytotoxicity and micronucleus formation, believed to reflect carcinogenic initiation, are enhanced in UGT-deficient rat fib...