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

Abstract

A heat-labile protein has been detected in microsomes from human liver which catalyzes the formation of glucosides of the bile acids chenodeoxycholic, deoxycholic, and ursodeoxycholic acids. This glucosyltransferase activity has been purified about 900-fold from human liver microsomes, resulting in homogeneity as determined by sodium dodecyl sulfate gel electrophoresis. The subunit molecular weight was calculated to be about 56,000. The catalyzed by a sugar nucleotide-independent glucosyltransferase and is therefore distinct from the known mechanisms of glycoside conjugation.

Mutation of β-glucosidase 2 causes glycolipid storage disease and impaired male fertility

“…Bile acid glucosidase and transferase activities were determined as described previously (10,16). Glucosylceramidase activity was assessed as described previously (29).…”

“…Bile acid glucosides, in which glucose is attached in β-linkage to carbon 3 of the bile acid (14), are normally excreted in the urine (15). Their synthesis by the liver is thought to assist in the disposal of hepatotoxic bile acids (16,17). Although GBA1 and GBA2 are both glycolipid hydrolases, the 2 enzymes apparently act on different glycolipids, do not share sequence identity, and are expressed in different tissues and subcellular compartments.…”

Purification and Characterization of a Microsomal Bile Acid β-Glucosidase from Human Liver

“…2 and 3). The position of the glucose moiety in these bile acid glucosides has been determined from enzymatically synthesized bile acid glucosides to be the 3-position (4) with a ␤-glucosidic linkage (1). The physiological significance of bile acid 3-O-glucosidation is suggested by the identification of glucosides of unconjugated as well as glycine-and taurine-conjugated bile acids in urine from healthy humans (5) and patients with extrahepatic cholestasis (6).…”

Bile acid N-acetylglucosaminidation. In vivo and in vitro evidence for a selective conjugation reaction of 7 beta-hydroxylated bile acids in humans.

“…Besides aminoacyl amidation with glycine or taurine (1) and sulfation (2), three glycosidic conjugation pathways have been established both in vivo and in vitro during the last years: glucuronidation (3,4), glucosidation (5,6), and Nacetylglucosaminidation (7,8). Semiquantitative estimates indicated a similar urinary excretion rate for the three glycosidic conjugates, at least in healthy humans (6,7,9,10).…”