title: Glucuronidation of polychlorinated biphenylols and UDP-glucuronic acid concentrations in channel catfish liver and intestine.
abstract: Polychlorinated biphenylols (OH-PCBs) are potentially toxic polychlorinated biphenyl metabolites that can be eliminated by glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs). OH-PCBs with a 3,5-dichloro-4-hydroxy substitution pattern have been detected in blood from humans and wildlife, suggesting slow elimination. In this study we assessed the glucuronidation of 4-OH-PCBs with zero, one, or two chlorine atoms flanking the 4-hydroxyl group and zero to four chlorine atoms in the aphenolic ring in microsomes from channel catfish liver and proximal intestine. Product formation was quantitated with [(14)C]UDP-glucuronic acid (UDPGA). Physiological concentrations of UDPGA were measured in preparations of liver and intestine. When the OH-PCB concentrations were varied in the presence of saturating UDPGA concentrations, glucuronidation V(max) values were higher in hepatic than in intestinal microsomes (0.40-3.4 and 0.12-0.78 nmol/min/mg of protein, respectively), whereas the K(m) values were generally lower for intestine (0.042-0.47 mM) than for liver (0.11-1.64 mM). In both tissues V(max) values with 3,5-dichloro-4-OH-PCBs were lower than with the corresponding 3-chloro-4-OH-PCBs. Varying the UDPGA concentrations in the presence of saturating concentrations of OH-PCB showed that the K(m) for UDPGA was lower in intestine (27 microM) than in liver (690 microM). The measured concentration of UDPGA in catfish liver (246-377 nmol/g) was lower than the K(m) for UDPGA, suggesting that in vivo rates of glucuronidation may be suboptimal, whereas in intestine the measured UDPGA concentration (71-258 nmol/g) was higher than the K(m) for UDPGA. Although liver has a greater glucuronidation capacity than proximal intestine, the properties of intestinal UGTs in channel catfish enable them to efficiently glucuronidate low concentrations of OH-PCBs.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, PO Box 100485, Gainesville, FL 32610-0485, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Sacco
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler
authors.forename: Larry W
authors.initials: LW
authors.lastname: Robertson
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Margaret O
authors.initials: MO
authors.lastname: James
mesh_terms: D000818:Animals; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism*; D007059:Ictaluridae / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism*; D014535:Uridine Diphosphate Glucuronic Acid / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020719:Glucuronides; D014535:Uridine Diphosphate Glucuronic Acid; D011078:Polychlorinated Biphenyls