Target intelligence / Profile preview

7-alpha-hydroxysteroid dehydrogenase (7-alpha-HSDH) (7-alpha-HSDH)

Target
7-alpha-HSDH
Molecular classification
Enzyme, Oxidoreductase, Short-chain dehydrogenase/reductase (SDR) family
01

Overview

7-alpha-hydroxysteroid dehydrogenase (7-alpha-HSDH), also known as cholanoate 7-alpha-dehydrogenase, is an oxidoreductase enzyme primarily localized within the human gut microbiota, including specific strains of Clostridium, Bacteroides, and Escherichia coli. It plays a pivotal role in the biotransformation of primary bile acids, such as cholic acid and chenodeoxycholic acid, by catalyzing the NAD(P)+-dependent oxidation of their 7-alpha-hydroxyl groups into 7-oxo intermediates. This enzymatic step is essential for the subsequent formation of secondary bile acids like ursodeoxycholic acid (UDCA), which serves as a vital signaling molecule and therapeutic agent. Industrially, 7-alpha-HSDH is highly valued as a biocatalyst for the commercial production of UDCA and its taurine conjugates used to treat gallstones and primary biliary cholangitis. Beyond synthesis, the enzyme is a target for microbiome-modulating therapies aimed at addressing metabolic disorders, irritable bowel syndrome, and liver injury, where bile acid pool composition is dysregulated. In clinical research, products of this enzyme's activity are also utilized as biomarkers to assess the pharmacodynamic effects of drugs targeting human steroid-modifying enzymes such as 11-beta-hydroxysteroid dehydrogenase type 1.

Other names
Cholanoate 7-alpha-dehydrogenase7-alpha-hydroxy steroid dehydrogenaseBile acid 7-alpha-dehydrogenase7-alpha-hydroxysteroid:NAD+ 7-oxidoreductase
02

Mechanism of action

Biocatalytic biotransformation of primary bile acids into therapeutic secondary bile acids (e.g., UDCA) and modulation of the intestinal bile acid pool to regulate host farnesoid X receptor (FXR) and TGR5 signaling pathways.

03

Biological functions

Bile acid metabolismSecondary bile acid biosynthesisEpimerization of primary bile acidsGut-liver axis signalingMaintenance of cholesterol homeostasis
04

Disease associations

Cholesterol gallstonesPrimary biliary cholangitisMetabolic syndromeInflammatory bowel diseaseType 2 diabetes mellitusColorectal cancer
05

Safety considerations

Induction of gut microbial dysbiosisUnintended systemic metabolic alterations through disrupted bile acid signalingPotential accumulation of toxic secondary bile acid intermediates if pathway balance is disrupted
06

Interacting drugs

Ursodeoxycholic acid

4 more in the full profile.

07

Biomarkers

7-oxolithocholic acid (7-oxo-LCA) levelsUrsodeoxycholic acid/7-oxolithocholic acid (UDCA/7-oxo-LCA) ratioFecal secondary bile acid profilesGut microbial 7-alpha-HSDH gene abundance

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