TY - JOUR T1 - 13-Hydroxy- and 13-Oxooctadecadienoic acids: Novel Substrates for Human UDP-Glucuronosyltransferases JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 652 LP - 655 VL - 29 IS - 5 AU - Anthony R. Jude AU - Joanna M. Little AU - Arthur W. Bull AU - Izabela Podgorski AU - Anna Radominska-Pandya Y1 - 2001/05/01 UR - http://dmd.aspetjournals.org/content/29/5/652.abstract N2 - Although there are numerous studies of glucuronidation of endogenous compounds, information on the glucuronidation of fatty acids is lacking. In the present studies, both linoleic acid (LA) and its biologically active oxidized derivatives, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO), have been shown to be effective substrates for human liver UDP-glucuronosyltransferases (UGT) and recombinant UGT2B7. LA (carboxyl glucuronide) and 13-OXO (carboxyl glucuronide, unproven) were actively glucuronidated by human liver microsomes (HLM) and human recombinant UGT2B7 with similar activities, in the range of 2 nmol/mg · min. The hydroxyl derivative of LA, 13-HODE, was glucuronidated at both the hydroxyl and carboxyl functions with carboxyl glucuronidation predominating (ratio of COOH/OH, 2:1). For all substrates, the Kmfor formation of the carboxyl-linked glucuronide was in the range of 100 to 200 μM while that for the hydroxyl-linked glucuronide was somewhat lower (>100 μM). This is the first demonstration of glucuronidation of LA and its oxidized derivatives, 13-HODE and 13-OXO, by HLM and recombinant UGT2B7. The American Society for Pharmacology and Experimental Therapeutics ER -