期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 389, 期 2, 页码 176-186出版社
ELSEVIER SCIENCE INC
DOI: 10.1006/abbi.2001.2344
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资金
- NIDDK NIH HHS [DK45123, DK51971, DK49715] Funding Source: Medline
- NIGMS NIH HHS [GM56708] Funding Source: Medline
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 EA-diols. Kinetic analysis with UGT2B7 yielded 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 excellent substrates for intestinal UGTs and provide the first evidence for UGT2B7 being the major isoform involved. (C) 2001 Academic Press.
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