1. Glucuronidation of catechols by human hepatic, gastric, and intestinal microsomal UDP-glucuronosyltransferases (UGT) and recombinant UGT1A6, UGT1A9, and UGT2B7.
- Author
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Antonio L, Xu J, Little JM, Burchell B, Magdalou J, and Radominska-Pandya A
- Subjects
- Adolescent, Adult, Animals, Blotting, Western, Catechols analysis, Cells, Cultured, Female, Glucuronates analysis, Glucuronosyltransferase genetics, Glucuronosyltransferase metabolism, Humans, Kinetics, Male, Microsomes enzymology, Middle Aged, Organ Specificity, Recombinant Proteins genetics, Recombinant Proteins metabolism, Spectrometry, Mass, Electrospray Ionization methods, UDP-Glucuronosyltransferase 1A9, Catechols metabolism, Gastric Mucosa enzymology, Glucuronates metabolism, Intestinal Mucosa enzymology, Liver enzymology
- 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.
- Published
- 2003
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