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Glucuronidation of Polychlorinated Biphenylols and UDP-Glucuronic Acid Concentrations in Channel Catfish Liver and Intestine

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida (J.C.S., W.L., M.O.J.); and Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa (H.-J.L., L.W.R.)

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 [¹⁴C]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 µM) than in liver (690 µM). 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.