Membrane-bound estrone as substrate for microsomal UDP-glucuronyltransferase.

Abstract

Nonpolar substrates of microsomal UDP-glucuronyl-transferase partition between the hydrophobic phase of the microsomal membrane and the bulk aqueous phase in a suspension of microsomes in water. Partitioning of estrone into the membranes was measured in the studies presented and was extensive. Comparison of the rate of conjugation of estrone and the rate of its release from microsomes into the bulk aqueous phase showed that the pool of estrone within the membrane is the substate for UDP-glucuronyl-transferase. The rate of conjugation of estrone was 6-fold greater than the rate of release of estrone from the membrane into the aqueous phase. Several additional experiments showed that the rate of glucuronidation of estrone did not depend on the amount of estrone in the bulk aqueous phase. It is concluded that the microsomal membrane serves to concentrate nonpolar substrates of UDP-glucuronly-transferase. The phospholipid region of the microsomal membrane also may be a co-factor of UDP-glucuronyltransferase in the sense that binding of estrone to the membrane restricts its orientation in a manner that facilitates catalysis.