Glucuronidation of linoleic acid diols by human microsomal and recombinantUDP-glucuronosyltransferases: Identification of UGT2B7 as the major isoform involved

Recent reports suggest that linoleic acid (LA) epoxides and diols are assoc iated with important physiological, pharmacological, and pathological event s in vivo. We have shown recently that LA-diols are excellent substrates fo r human liver microsomal UDP-glucuronosyltransferases (UGTs); however, it i s not known if other human tissues glucuronidate LA-diols or which UGT isoz yme(s) is involved. The present studies with human intestinal microsomes in dicate that glucuronidation of LA-diols occurs throughout the gastrointesti nal tract, with the highest activity in the small intestine. LA-diols yield ed exclusively hydroxyl-linked glucuronides, whereas LA yielded the carboxy l-linked glucuronide, Studies with human recombinant UGTs demonstrated that only UGT2B7 glucuronidated LA and EA-diols. Kinetic analysis with UGT2B7 y ielded apparent K-m values in the range of 40-70 muM and V-max values from 4.5 to 5.4 nmol/mg x min. These studies indicate that EA and LA-diols are e xcellent substrates for intestinal UGTs and provide the first evidence for UGT2B7 being the major isoform involved. (C) 2001 Academic Press.