title: Glucuronidation of linoleic acid diols by human microsomal and recombinant UDP-glucuronosyltransferases: identification of UGT2B7 as the major isoform involved.
abstract: Recent reports suggest that linoleic acid (LA) epoxides and diols are associated with important physiological, pharmacological, and pathological events in vivo. We have shown recently that LA-diols are excellent substrates for human liver microsomal UDP-glucuronosyltransferases (UGTs); however, it is not known if other human tissues glucuronidate LA-diols or which UGT isozyme(s) is involved. The present studies with human intestinal microsomes indicate that glucuronidation of LA-diols occurs throughout the gastrointestinal tract, with the highest activity in the small intestine. LA-diols yielded exclusively hydroxyl-linked glucuronides, whereas LA yielded the carboxyl-linked glucuronide. Studies with human recombinant UGTs demonstrated that only UGT2B7 glucuronidated LA and LA-diols. Kinetic analysis with UGT2B7 yielded apparent K(m) values in the range of 40-70 microM and V(max) values from 4.5 to 5.4 nmol/mg x min. These studies indicate that LA and LA-diols are excellent substrates for intestinal UGTs and provide the first evidence for UGT2B7 being the major isoform involved.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Jude
authors.forename: J M
authors.initials: JM
authors.lastname: Little
authors.forename: P J
authors.initials: PJ
authors.lastname: Czernik
authors.forename: T R
authors.initials: TR
authors.lastname: Tephly
authors.forename: D F
authors.initials: DF
authors.lastname: Grant
authors.forename: A
authors.initials: A
authors.lastname: Radominska-Pandya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008041:Linoleic Acids / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D020719:Glucuronides; D007527:Isoenzymes; D008041:Linoleic Acids; D011994:Recombinant Proteins; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase