Stimulation of hepatic microsomal beta-glucuronidase by calcium.
Hydrolysis of 3-methylumbelliferyl glucuronide by liver microsomal beta-glucuronidase is enhanced about 2-fold by micromolar concentrations of Ca2+; half-maximal stimulation occurs with 0.35 microM Ca2+. Dissociation of the enzyme from microsomal membranes by various treatments increases basal beta-glucuronidase activity and markedly decreases the sensitivity of the enzyme to Ca2+. Under similar conditions, the soluble lysosomal form of the enzyme is insensitive to Ca2+. Ca2+ stimulation was unaltered by addition of calmodulin inhibitors or exogenous calmodulin. Thus, interaction of cytosolic Ca2+ with membrane bound beta-glucuronidase may modulate glucuronidation in intact hepatocytes via a novel, calmodulin-independent mechanism.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000201:enzymology; D013347:Subcellular Fractions / Q000201:enzymology
D002147:Calmodulin; D005966:Glucuronidase; D002118:Calcium