4-OHBP in the intestine was also the lowest. In the liver however, the Km was

comparable to other OH-PCBs. These results are surprising in view of the fact that 4-

OHBP has been shown to be a good substrate for glucuronidation using rat, guinea pig,

beagle dog and rhesus monkey liver microsomes (Yoshimura et al., 1992), and human

expressed UGTs (King et al., 2000; Ethell et al., 2002). In isolated rat hepatocytes, 4-

OHBP is a cytotoxic major metabolite of biphenyl, impairing oxidative phosphorylation

(Nakagawa et al., 1993). These results suggest that this compound may be potentially

more toxic to catfish than to mammals, unless cleared by another pathway such as

sulfonation.

 While the decreased glucuronidation of 4-OHBP may be due to the lack of a

specific phenol UGT isoform in catfish, the known broad substrate specificity of phenol

UGTs, together with the observed higher rates of glucuronidation for the OH-PCBs, leads

us to hypothesize that this compound may be such a poor substrate due to its lower

lipophilicity, as has been observed for other substituted phenols (Kim 1991). In fact,

addition of a single chlorine atom flanking the phenolic group (as represented by

40HCB2) resulted in at least a tenfold increase in Vmax in both liver and intestine, with no

significant change in Km (with respect to 4-OHBP). This increased lipophilicity

(represented by an estimated log P increase from 3.2 to 3.8) appeared to impact the

formation of the glucuronide and not the initial binding of substrate to UGT. Good UGT

substrates tend to be lipophilic compounds which are thought to diffuse through the

endoplasmic reticular bilayer and reach the substrate-binding site in the lumenal N-

terminal part of the enzyme, which contains a region of strong interaction with the

membrane (Radominska-Pandya et al., 2005). For all the OH-PCBs studied, we only