title: Glucuronidation of catechols by human hepatic, gastric, and intestinal microsomal UDP-glucuronosyltransferases (UGT) and recombinant UGT1A6, UGT1A9, and UGT2B7.
abstract: The substrate specificity of human gastric and intestinal UDP-glucuronosyltransferases (UGTs) toward catechols was investigated and compared to that of liver UGTs. Small catechols were efficiently glucuronidated by stomach (0.8-10.2 nmol/mgprotein x min) and intestine (0.9-7.7 nmol/mgprotein x min) with activities in a range similar to those found in liver (2.9-19 nmol/mgprotein x min). Large interindividual variations were observed among the samples. Immunoblot analysis demonstrated the presence of UGT1A6 and UGT2B7 in stomach and throughout the intestine. Recombinant human UGT1A6, 1A9, and 2B7, stably expressed in mammalian cells, all effectively catalyzed catechol glucuronidation. K(m) values (0.09-13.6mM) indicated low affinity for UGTs and V(max) values ranged from 0.51 to 64.0 nmol/mgprotein x min. These results demonstrate for the first time glucuronidation of catechols by gastric and intestinal microsomal UGTs and three human recombinant UGT isoforms.
authors.affiliation: UMR 7561 CNRS-University Henri Poincaré-Nancy I, Vandoeuvre-les-Nancy, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Antonio
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Little
authors.forename: Brian
authors.initials: B
authors.lastname: Burchell
authors.forename: Jacques
authors.initials: J
authors.lastname: Magdalou
authors.forename: Anna
authors.initials: A
authors.lastname: Radominska-Pandya
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002396:Catechols / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology*; D005965:Glucuronates / Q000032:analysis / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D002396:Catechols; D005965:Glucuronates; D011994:Recombinant Proteins; C000715591:UGT1A9 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9