Formation of bile acid glucosides by a sugar nucleotide-independent glucosyltransferase isolated from human liver microsomes.

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Abstract
A heat-labile protein was detected in microsomes from human liver which catalyzes the formation of glucosides of the bile acids chenodeoxycholic, deoxycholic and ursodeoxycholic acids. This glucosyltransferase activity was purified about 900-fold from human liver microsomes, resulting in homogeneity as determined by sodium dodecyl sulfate gel electrophoresis. The subunit MW was calculated to be .apprx. 56,000. The enzyme was separated from bile acid UDP-glucuronosyltransferase [UDP-glucuronate .beta.-D-glucuronosyltransferase (acceptor-unspecific), EC 2.4.1.17] during purification and does not catalyze the formation of bile acid glucuronides. The purified glucosyltransferase utilizes lipophilic alkyl .beta.-D-glucopyranosides as artificial donor substrates and dolichyl phosphoglucose as natural donor for the transfer of glucose to bile acids and does not exhibit bile acid conjugating activity in the presence of sugar nucleotides such as UDP-glucose. The apparent Km values estimated for various alkyl .beta.-D-glucopyranosides decreased with increasing alkyl chain length from 680 .times. 10-6 M for hexyl .beta.-D-glucopyranoside to 20 .times. 10-6 M as estimated for decyl and dodecyl .beta.-D-glucopyranoside. The results suggest that a glucoside-conjugation pathway of bile acids exists in humans. This conjugation is catalyzed by a sugar nucleotide-independent glucosyltransferase and is therefore distinct from the known mechanisms of glycoside conjugation.