Uridine 5-diphosphate-glucuronosyltransferase

5 Uridine Diphosphate Glucuronosyltransferase (Matsul and Nagal, 1980 To and Weils, 1984) 

Uridine diphosphate glucuronosyltransferase catalyzes the transfer of glucuronic acid from uridine diphosphate glucuronic acid (UDPGA) to various 

The enzyme was prepared from rat liver. A homogenate was prepared in sucrose with a Teflon-glass homogenizer. A series of differential centrifugations (2000g for 10 min, 16,000 for 45 min, and 105,000 for 60 min) produced a microsomal pellet that was used as the enzyme source. 

In a study by To and Wells (1984), the glucuronic acid was transferred from UDPGA to the acceptor, a-naphthol. In this assay the substrate a-naphthol was separated from the reaction product a-naphthol glucuronide by reversed-phase HPLC (Ci8 column) with a solvent of 0.1 M acetic acid-methanol (55 45, v/v). Absorbance was monitored at 240 nm. 

The reaction mixture contained the substrate, a-naphthol (5.0 mAf), in Tris-HCl buffer (pH 7.4) with 10 vaM magnesium chloride and DMSD. The second substrate, UDPGA, was added, and the reaction mixture was preincubated for 5 minutes. The microsomal protein was then added as the source 

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Kaivosaari S, Salonen JS, Mortensen J, Taskinen J. High-performance liquid chromatographic method combining radiochemical and ultraviolet detection for determination of low activities of uridine 5 -diphosphate-glucuronosyltransferase. A a/yft ca/ Biochemistry 292, 178-187, 2001. 

Debinski HS, Lee CS, Danks JA, et al. (1995) Localization of uridine 5 -diphosphate-glucuronosyltransferase in hnman liver injury. Gastroenterology 108 1464-1469. 

Mackenzie PI, Rodbourn L, lyanagi T. 1993. Glucuronidation of carcinogen metabolites by complementary DNA-expressed uridine 5 -diphosphate glucuronosyltransferases. Cancer Res 53 1529-1533. 

Smith PA, Sorich MJ, McKinnon RA, Miners JO. In silico insights chemical and structural characteristics associated with uridine diphosphate-glucuronosyltransferase substrate selectivity. Clin Exp Pharmacol Physiol 2003 30 836-40. 

Meech, R. and Mackenzie, PI. (1997) Structure and function of uridine diphosphate glucuronosyltransferase. Clinical and Experimental Pharmacology Physiology, 24, 907-915. 

Iyer L, King CD, Whitington PF et al. Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 1998 101 847-854. 

Hall D, Ybazeta G, Destro-Bisol G et al. Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 1999 9 591-599. 

Phenobarbital, phenytoin, primidone, and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate glucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzyme systems and displaces some drugs from plasma albumin. 

Nicotine glucmonidation results in an N-quatemary glucmonide in humans (Benowitz et al. 1994). This reaction is catalyzed by uridine diphosphate-glucuronosyltransferase (UGT) enzyme(s) producing (5)-nicotine-N-P-glucmonide. About 3-5% of nicotine is converted to nicotine glucuronide and excreted in urine in humans. 

Uridine diphosphate glucuronosyltransferase, more specifically UGTIAI, is capable of glucuronidating bilirubin. The clinically relevant polymorphisms related to genetic abnormalities in the UGTIAI enzyme are those associated with familial... 

Font A, Sanchez JM, Taron M et al. Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase lAl (UGTIAI) polymorphism. Invest New Drugs 2003 21 435 43. 

Akaba K, Kimura T, Sasaki A, et al. Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene a common missense mutation among Japanese, Koreans and Chinese. Biochem Mol Biol Int 1998 46 (1) 21—26. 

Jin C, Miners JO, Lillywhite KG, et al. Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther 1993 264... 

Sawyer MB, Innocenti F, Das S, et al. A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine. Clin Pharmacol Ther 2003 73(6) 566-574. 

Chouinard S, Pelletier G, Belanger A, et al. Isoform-specific regulation of uridine diphosphate-glucuronosyltransferase 2B enzymes in the human prostate differential consequences for androgen and bioactive lipid inactivation. Endocrinology 2006 ... 

Girard C, Barbier O, Veilleux G, et al. Human uridine diphosphate-glucuronosyltransferase UGT2B7 conjugates mineralocorticoid and glucocorticoid metabolites. Endocrinology 2003 144(6) 2659-2668. 

Concurrent use of oxcarbazepine with ethinyl estradiol and levonoi estrel-containing contraceptives may render these agents less effective. Qxcar-bazepine may increase serum concentrations of phenytoin and decrease serum concentrations of lamotrigine (induction of uridine diphosphate glucuronosyltransferase). 

Perera MA, Innocenti F, Ratain MJ (2008) Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms are we there yet Pharmacotherapy 28 755-768... 

O Dwyer PJ, Catalano RB. Uridine diphosphate glucuronosyltransferase (UGT) lAl and irinotecan practical pharmacogenomics arrives in cancer therapy. J Clin Oncol 2006 24(28) 4534-8. 

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