UDP-glucuronosyltransferase enzymes

Guillemette C. Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J 2003 3(3) 136—158. 

Belanger A, Pelletier G, Labrie F, et al. Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab 2003 14 (10) 473 179. 

A. Ghosal, N. Hapangama, Y. Yuan, J. Achanfuo-Yeboah, R. lannucci, S. Chowdhury, K. Alton, J. E. Patrick, and S. Ziaida, Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (ZETIA), Drug Metab. Dispos. 32 (2004), 314-320. 

UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab 2003 14 473-479. 

Recently, Van der Logt et al. demonstrated that curcumin exerted its anticarcinogenic effects in gastrointestinal cancers through the induction of UDP-glucuronosyltransferase enzymes. 

Zhang D, Wang L, Chandrasena G, Ma L, Zhu M, Zhang H, Davis CD, Humphreys WG. Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar. Drug Metab Dispos 2007 35 139-149. 

Similar to 5-FU, there is a polymorphism associated with irinotecan toxicity. UDP-glucuronosyltransferase (UGT1A1) is an enzyme responsible for the glucuronidation of SN-38 to inactive metabolites, and reduced or deficient levels of this enzyme correlate with irinotecan-induced diarrhea and neutropenia.39 Recently the FDA approved a blood test that detects variations in this gene. This test will assist health care providers in predicting which patients may develop severe toxicities from normal doses of irinotecan and can be ordered prior to patients receiving irinotecan. binotecan is administered as an IV bolus over 60 to 90 minutes in a variety dosing schedules. 

Miley, M.J., Zielinska, A.K., Keenan, J.E., Bratton, S.M., Pandya, A.R. andRedinbol, M.R. (2007) Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7. Journal of Molecular Biology,... 

There is no information regarding the metabolism of 3,3 -dichlorobenzidine in children. However, N-acetylation (as discussed above) in humans is likely done by one of two families of N-acetyltransferases. One of these families, NAT2, is developmentally regulated (Leeder and Kearns 1997). Some enzyme activity can be detected in the fetus by the end of the first trimester. Almost all infants exhibit the slow acetylator phenotype between birth and 2 months of age. The adult phenotype distribution is reached by the age of 4-6 months, whereas adult activity is found by approximately 1-3 years of age. Also, UDP-glucuronosyltransferase, responsible for the formation of glucuronide conjugates, seems to achieve adult activity by 6-18 months of age (Leeder and Kearns 1997). These data suggest that metabolism of 3,3 -dichlorobenzidine by infants will differ from that in adults in extent, rate, or both. 

This set of enzymes [EC 2.4.1.17], also known as UDP-glucuronosyltransferases, catalyzes the reaction of UDP-glucuronate with an acceptor to produce UDP and the 13-D-glucuronoside of the acceptor. This family of proteins accepts a wide range of substrates, including phenols, alcohols, amines, and fatty acids. 

Wen Z, Tallman MN, Ali SY, et al. UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes structural characterization of phenolic and alcoholic glu-curonides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos 2007 35(3) 371-380. 

Chouinard S, Tessier M, Vemouillet G, et al. Inactivation of the pure antiestrogen fulvestrant and other synthetic estrogen molecules by UDP-glucuronosyltransferase 1A enzymes expressed in breast tissue. Mol Pharmacol 2006 69(3) 908-920. 

Soars MG, Ring BJ, Wrighton SA. The effect of incubation conditions on the enzyme kinetics of udp-glucuronosyltransferases. Dmg Metab Dispos 2003 31(6) 762-767. 

Haumont M, Magdalou J, Lafaurie C, et al. Phenobarbital inducible UDP-glucuronosyltransferase is responsible for glucuronidation of 3 -azido-3 -deoxythymidine characterization of the enzyme in human and rat liver microsomes. Arch Biochem Biophys 1990 281(2) 264-270. 

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