Received for publication November 2, 2007.
Revised December 27, 2007.
Accepted for publication January 2, 2008.

Glucuronidation of polychlorinated biphenylols and UDPGA concentration in channel catfish liver and intestine

Abstract

Polychlorinated biphenylols (OH-PCBs) are potentially toxic PCB 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. This study assessed the glucuronidation of 4-OH-PCBs with 0, 1 or 2 Cl atoms flanking the 4-hydroxyl group, and 0 to 4 Cl atoms in the aphenolic ring, in microsomes from channel catfish liver and proximal intestine. Product formation was quantitated with ¹⁴C- UDP-glucuronic acid (UDPGA). Physiologic concentrations of UDPGA were measured in preparations of liver and intestine. When varying the OH-PCB concentrations in the presence of saturating UDPGA concentrations, glucuronidation V_max values were higher in hepatic than intestinal microsomes (0.40-3.4 and 0.12-0.78 nmole/min/mg protein, respectively), while the Km values were generally lower for intestine (0.042-0.47 mM) than 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 the Km for UDPGA was lower in intestine (27 µM) than liver (690 µM). The measured concentration of UDPGA in catfish liver (246 to 377 nmole/g) was lower than the Km for UDPGA, suggesting in vivo rates of glucuronidation may be sub-optimal, while in intestine the measured UDPGA concentration (71 to 258 nmole/g) was higher than the K_m for UDPGA. Although liver has greater glucuronidation capacity than proximal intestine, the properties of intestinal UGTs in channel catfish enable them to efficiently glucuronidate low concentrations of OH-PCBs.

Key words: environmental toxicology, glucuronidation, microsomes, phase II drug metabolism, UDP glucuronyltransferases