Glucuronidation of polychlorinated biphenylols and UDP-glucuronic acid concentrations in channel catfish liver and intestine.
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.
Sacco
James C
JC
Department of Medicinal Chemistry, University of Florida, PO Box 100485, Gainesville, FL 32610-0485, USA.
Lehmler
Hans-Joachim
HJ
Robertson
Larry W
LW
Li
Wenjun
W
James
Margaret O
MO
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*
D020719:Glucuronides; D014535:Uridine Diphosphate Glucuronic Acid; D011078:Polychlorinated Biphenyls