Structural requirements of the human sodium-dependent bile acid transporter (hASBT): role of 3- and 7-OH moieties on binding and translocation of bile acids.

ABSTRACT: Bile acids (BAs) are the end products of cholesterol metabolism. One of the critical steps in their biosynthesis involves the isomerization of the 3β-hydroxyl (-OH) group on the cholestane ring to the common 3α-configuration on BAs. BAs are actively recaptured from the small intestine by the human Apical Sodium-dependent Bile Acid Transporter (hASBT) with high affinity and capacity. Previous studies have suggested that no particular hydroxyl group on BAs is critical for binding or transport by hASBT, even though 3β-hydroxylated BAs were not examined. The aim of this study was to elucidate the role of the 3α-OH group on BAs binding and translocation by hASBT. Ten 3β-hydroxylated BAs (Iso-bile acids, iBAs) were synthesized, characterized, and subjected to hASBT inhibition and uptake studies.

SUBMITTER: Gonzalez PM 

PROVIDER: S-EPMC4031276 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature