Structure-Function Relationships of 3ß-Hydroxysteroid Dehydrogenases Involved in Bile Acid Metabolism

Abstract

In vertebrates, 3 β-hydroxysteroid dehydrogenases (3β-HSDs) fulfill several physiological and metabolic functions. They are primarily involved in the synthesis of all classes of steroid hormones by catalyzing the 3β-OH dehydrogenation/Δ4–5 isomerization of steroid hormone precursor molecules (Simard et al., 1996). In mammals they furthermore mediat3-hydroxyl group epimerization of bile acids and other steroids during en-terohepatic circulation (Figure 1). The enzymes involved in this reaction comprise 3σ-x-hydroxysteroid dehydrogenases (3a-HSD), 3-keto reductases and 3β-HSDs. Epimerization of steroids secreted in the bile occurs in the intestine, catalyzed by microbial hydroxysteroid dehydrogenases and in the liver. The importance of these epimerization reactions is unknown, but it is anticipated that liver 3β-HSDs are involved in intracellular bindinnd transport of bile acids from the sinusoidal to the canalicular side of the hepatocyte thus might play a role in cholestatic processes (Marschall et al., 1998).