Defective induction of phenol glucuronidation by 3-methylcholanthrene in Gunn rats is due to the absence of a specific UDP-glucuronosyltransferase isoenzyme.
Antiserum directed against purified rat kidney UDP-glucuronosyltransferase (UDPGT) was raised in goats. IgG prepared from this antiserum exhibited specificity for only two UDPGT isoenzymes (bilirubin and phenol) on immunoblot analysis of Wistar rat liver microsomes. Use of this antibody preparation to probe Western blots of liver microsomes prepared from Gunn rats confirmed that the defective phenol glucuronidation was due to the absence of a 53-kDa, 3-methylcholanthrene-inducible UDPGT isoenzyme. Results obtained from enzyme activity measurements and immunoblot analysis of microsomes isolated from xenobiotic-treated Wistar and Gunn rat liver are consistent with the 3-methylcholanthrene/UDPGT induction deficiency in the Gunn rat being due to the absence of this phenol UDPGT isoenzyme. The contribution of other UDPGT isoenzymes to the greatly reduced glucuronidation of planar phenols observed in the Gunn rat is discussed.
D000818:Animals; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000172:deficiency* / Q000378:metabolism; D007527:Isoenzymes / Q000172:deficiency* / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009284:Naphthols / Q000378:metabolism; D019800:Phenol; D010636:Phenols / Q000378:metabolism; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013739:Testosterone / Q000378:metabolism
D005965:Glucuronates; D007527:Isoenzymes; D009284:Naphthols; D010636:Phenols; D019800:Phenol; D013739:Testosterone; D008748:Methylcholanthrene; D014453:Glucuronosyltransferase