Stimulation of 3-benzo[a]pyrenyl glucuronide hydrolysis by calcium activation of microsomal beta-glucuronidase

Rates of hydrolysis of 3-hydroxybenzo[a]pyrenyl glucuronide by microsomal beta-glucuronidase from rat liver were 397 +/- 17 nmol/min per g protein and were half-maximal with about 100 microM substrate. Treatment of rats with phenobarbital or 3-methylcholanthrene, which elevates activities of glucuronosyltransferase(s), lowered rates of hydrolysis of benzo[a]pyrene glucuronide by 25%. Hydrolysis of the glucuronide by microsomal beta-glucuronidase was stimulated by micromolar concentrations of calcium in the range existing in cytosol of hepatocytes (apparent Km approximately 0.2 microM). Thus, humoral factors that change intracellular concentrations of free calcium may alter the production and export of glucuronides of benzo[a]pyrene metabolites from the liver.