Multiple forms and a deficiency of uridine diphosphate-glucuronosyltransferases in Wistar rats.
Uridine diphosphate (UDP)-glucuronosyltransferase (GT) active on androsterone (AD) and 4-nitrophenol (NP) was solubilized from male rat liver microsomes of the Wistar strain. The precipitate obtained in the 60%-satd. ammonium sulfate was purified by diethylaminoethyl (DEAE)-cellulose chromatography and affinity chromatography on UDP-hexanolamine Sepharose 4B. DEAE-cellulose chromatography showed the existence of two peaks of GT active on AD and NP. Peak I was found in rats with the high-activity and low-activity phenotypes in terms of AD glucuronidation and had high NP-GT and low AD-GT activities. In contrast, peak II was found only in rats with the high-activity phenotype, corresponded to high AD-GT activity and had comparatively low NP-GT activities. The corresponding peak in rats with the low-activity phenotype had only NP-GT activity. Comparison of Km values for AD obtained from microsomes and purified enzymes provides evidence that AD-GT isoenzyme should be deficient in Wistar rats with the low-activity phenotype and that AD glucuronidation should be catalyzed poorly by other GT isoenzyme in these rats.
D000818:Animals; D002848:Chromatography, DEAE-Cellulose; D004591:Electrophoresis, Polyacrylamide Gel; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000032:analysis* / Q000172:deficiency; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis* / Q000172:deficiency; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
D005965:Glucuronates; D007527:Isoenzymes; D014453:Glucuronosyltransferase