PT - JOURNAL ARTICLE AU - Otito Frances Iwuchukwu AU - Jumoke Ajetunmobi AU - Din Ung AU - Swati Nagar TI - Characterizing the Effects of Common UDP Glucuronosyltransferase (UGT) 1A6 and UGT1A1 Polymorphisms on <em>cis-</em> and <em>trans</em>-Resveratrol Glucuronidation AID - 10.1124/dmd.109.027391 DP - 2009 Aug 01 TA - Drug Metabolism and Disposition PG - 1726--1732 VI - 37 IP - 8 4099 - http://dmd.aspetjournals.org/content/37/8/1726.short 4100 - http://dmd.aspetjournals.org/content/37/8/1726.full SO - Drug Metab Dispos2009 Aug 01; 37 AB - The dietary polyphenol resveratrol (RES) exists as cis- and trans-isomers with known stereospecific and stereoselective glucuronidation at the 3 and 4′ positions by distinct UGT1A isoforms. We examined cis-RES glucuronidation in various protein sources. UGT1A6 or UGT1A1 genotype-dependent cis-or trans-RES glucuronidation, respectively, was further determined. cis-RES exhibited partial substrate inhibition in UGT1A6 Supersomes and human embryonic kidney 293 cells overexpressing genetically variant UGT1A6 alleles. Cells expressing UGT1A6*4 had the highest activity with a Vmax of 612 ± 27.36 nmol/min/mg, followed by UGT1A6*3. The *2 allozyme had a higher Vmax (1.6-fold) and Km (1.9-fold) than *1. In 51 human liver samples genotyped for UGT1A6, four alleles (frequencies) were identified as *1 (0.58), *2 (0.36), *3 (0.01), and *4 (0.05), leading to assignment of the following genotypes (frequencies): *1/*1 (0.29), *1/*2 (0.45), *1/*3 (0.02), *1/*4 (0.10), and *2/*2 (0.14). Up to 5-fold variability in trans-RES glucuronidation was observed in individual liver samples. In livers stratified by UGT1A6 genotype, a significant difference in cis-RES glucuronidation activity (p &lt; 0.05) was seen between the *2 variants compared with homozygous *1 livers. The trans-RES glucuronidation was quantitated in a human liver bank genotyped for the UGT1A1 TATA box repeat polymorphism. There was no significant difference for formation of trans-RES 3-O-glucuronide. We were surprised to find that trans-RES 4′-O-glucuronide formation was higher in livers with the 7/7 genotype compared with 6/6 and 6/7 (p &lt; 0.05). In conclusion, cis-RES glucuronidation exhibited atypical partial substrate inhibition kinetics in vitro. Whereas cis-RES glucuronidation varied with UGT1A6 genotypes, the UGT1A1*28 polymorphism did not explain variability in trans-RES glucuronidation.