Inhibition of P-Glucuronidase by Cholesterol and Retinal*

The relatively specific inhibition of &glucuronidase by cholesterol and retinol (vitamin A alcohol) has been studied. Both hydrolysis and transfer reactions are inhibited. The hydrolysis reaction is inhibited 70% by 1 X low4 M retinol and by 7.8 X lo+ M cholesterol. Inhibition increases with concentration and approaches an asymptotic maximum. fl-Glucuronidases tested from a wide variety of mammalian and nonmammalian sources were inhibited. Among known ,&glucuronidase activators, deoxyribonucleic acid reversed inhibition about 50% while proteins had less effect. Inhibition was constant with time, was reversible upon dilution, was uncompetitive, and the inhibitions of rednol and cholesterol were not additive. Addition of a-tocopherol or ubiquinone did not affect inhibition. Glutamate dehydrogenase and pyruvate kinase, known to be inhibited by steroid hormones, were tested. Glutamate dehydrogenase is inhibited 50 and 64%, respectively, by cholesterol and retinol at 1 X lop4 M; and pyruvate kinase is not inhibited. Blood serum inhibits the enzyme and inhibition is correlated with serum levels of cholesterol found in normal and abnormal serum standards. It is suggested that the previously reported “anti-glucuronidase” of blood serum may be cholesterol and that inhibition of /3-glucuronidase by cholesterol may occur in vivo.