Effects of Ca2+, Zn2+ and Cd2+ on uridine diphosphate-glucuronyltransferase and beta-glucuronidase activities in rat liver microsomes.
The effect of various metals on uridine diphosphate (UDP)-glucuronyltransferase and beta-glucuronidase activities in rat liver microsomes was investigated. The presence of Mn2+, Cd2+, Zn2+, V5+, Ni2+, Co2+, Cu+ or Ca2+ (20 microM) in the enzyme reaction mixture did not cause a significant alteration of UDP-glucuronyltransferase activity in hepatic microsomes. Of these metals, Zn2+ and Cd2+ (20 microM) caused a remarkable increase in hepatic microsomal beta-glucuronidase activity. Appreciable effects of Zn2+ and Cd2+ on beta-glucuronidase activity were seen at 5.0 microM, and the effects were saturated at 50 microM. Ca2+ (5.0-50 microM) and/or the Ca2(+)-binding protein regucalcin (2.0 microM) did not have an appreciable effect on UDP-glucuronyltransferase and beta-glucuronidase activities in hepatic microsomes. Thus, Zn2+ and Cd2+ uniquely increased beta-glucuronidase activity. The Zn2(+)- and Cd2(+)-induced increase in beta-glucuronidase activity was completely reversed by the presence of an SH group-protecting reagent (dithiothreitol). The response of the microsomal enzyme to Zn2+ and Cd2+ (20 microM) was no longer seen after treatment with 0.2% Triton X-100 [polyoxyethylene(10)octylphenyl ether], indicating that the stimulation by these metals is dependent on membrane association. The present study suggests that, of various metals tested, Zn2+ and Cd2+ can uniquely increase hepatic microsomal beta-glucuronidase activity and that their effect is based on binding to membranous SH groups, beside the enzyme protein.
Yamaguchi
M
M
Department of Environmental Biochemistry and Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Mori
S
S
Suketa
Y
Y
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases; D005966:Glucuronidase / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D015238:Sulfotransferases; D015032:Zinc / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D002104:Cadmium; D014453:Glucuronosyltransferase; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D002265:Carboxylic Ester Hydrolases; C513325:Rgn protein, rat; D005966:Glucuronidase; D015032:Zinc; D002118:Calcium