7dehydroxylation

7-dehydroxylation is the enzymatic removal of a hydroxyl group from the seventh carbon of a steroid nucleus. In mammalian bile acid metabolism, it describes the microbial conversion of primary bile acids into secondary bile acids by the gut microbiota. Cholate (3α,7α,12α-trihydroxy) is converted to deoxycholate (3α,12α-dihydroxy), and chenodeoxycholate (3α,7α-dihydroxy) is converted to lithocholate (3α-hydroxy). The overall process reduces the number of hydroxyl groups and increases hydrophobicity, influencing solubility and signaling.

Biochemically, 7α-dehydroxylation is a multi-step pathway carried out by anaerobic gut bacteria. It begins with oxidation of the 7α-hydroxyl group to a 7-oxo intermediate by 7α-hydroxysteroid dehydrogenases. Subsequent enzymatic steps remove the 7-oxo moiety to yield the 7-dehydro compound and, ultimately, the 7-deoxy bile acid. The precise sequence and enzyme architecture vary among species and are typically encoded by bile acid-inducible (bai) gene clusters (for example baiA, baiB, baiCD, baiE) in various Clostridium and Eubacterium members.

Significance: 7-dehydroxylation shapes the gut bile acid pool, influencing digestion and host signaling via receptors such as FXR and TGR5. Secondary bile acids like deoxycholate and lithocholate have distinct physicochemical properties and biological activities, contributing to normal physiology as well as being associated with certain disease states when unbalanced.