Influence of Membrane Lipids on the Regulatory Properties of UDP-Glucuronyltransferase.

The maximal potential activity of UDP-glucuronyltransferase is constrained by the structure of the phospholipid environment in intact microsomal membranes. This constraint can be relieved by treatment of microsomes with phospholipase A. As shown by the data in this paper, however, relief of constraint is associated with a loss of specificity in the binding of UDP-sugars at the UDP-glucuronic acid site of UDP-glucuronyltransferase. As a result, several UDP-sugars which have no effect on the activity of the untreated enzyme act as inhibitors of the unconstrained, phospholipase A-treated form of UDP-glucuronyltransferase. In addition to the loss of specificity of substrate binding, the phospholipase-A-treated form of UDP-glucuronyltransfease cannot be activated by UDP-N-acetylglucosamine, which is a positive K-type of allosteric effector for the untreated form of the enzyme. UDP-N-acetylglucosamine, in fact, is an inhibitor of the phospholipase-A-treated form of the enzyme. In contrast to the effects of other UDP-sugars, inhibition by UDP-N-acetylglucosamine seems to result from the binding of UDP-N-acetylglucosamine at an allosteric site rather than the active site. Inhibition of the phospholipase-A-treated form of UDP-glucuronyltransferase by UDP-N-acetylglucosamine and other UDP-sugars is additive. [ABSTRACT FROM AUTHOR]