Differential regulation by triiodothyronine of substrate-specific uridinediphosphoglucuronate glucuronosyl transferases in rat liver.
Hepatic uridinediphosphoglucuronate glucuronosyl transferase (UDPglucuronyltransferase, EC 2.4.1.17) is functionally heterogeneous; 4-nitrophenol and bilirubin are representative substrates for two functional forms of the enzyme. UDPglucuronyltransferase activity for bilirubin and 4-nitrophenol was separated from solubilized rat liver microsomes by DEAE-cellulose chromatography and corresponding enzymes were purified. A radioimmunoassay was developed using a rabbit antiserum against purified rat 4-nitrophenol-specific UDPglucuronyltransferase, which precipitated enzyme activities toward both 4-nitrophenol and bilirubin. After treatment with triiodothyronine (T3) (0.55 mg/kg body weight), hepatic microsomal UDPglucuronyltransferase activity for 4-nitrophenol was increased 400% as compared to controls; the enzyme activity for bilirubin was decreased by 80%; the changes in the substrate-specific enzyme activities were reflected in the enzymatically active fractions separated after DEAE-cellulose chromatography. The changes in enzyme activities paralleled changes in the concentrations of the two corresponding UDP glucuronyltransferase proteins in the chromatographic fractions, as measured by radioimmunoassay. The results indicate that the opposite effects of T3 on the two forms of UDPglucuronyltransferase activity is due to its differential effect on corresponding enzyme proteins.
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007120:Immunochemistry; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D014284:Triiodothyronine / Q000494:pharmacology*
D009596:Nitrophenols; D014284:Triiodothyronine; D014453:Glucuronosyltransferase; D001663:Bilirubin; C024836:4-nitrophenol