7alpha-dehydroxylation of cholic acid and chenodeoxycholic acid by bai operon genes (Homo sapiens)

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This pathway summarizes the gut bacterial 7α dehydroxylation of unconjugated primary bile acids, in which deconjugated cholic acid (CA) and chenodeoxycholic acid (CDCA) are converted to the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, by Firmicutes such as Clostridium and related genera that carry bile acid–inducible (bai) genes.

It follows a multi step bai operon–dependent route in which bile acids are transported into the cell and transformed through CoA thioester formation, sequential oxidations, a 7α dehydration step and subsequent reductions and CoA removal, highlighting the central roles of BaiB, BaiA2, BaiCD, BaiE, BaiF, BaiH and BaiN. Because no single consensus mechanism is fully established, the pathway explicitly shows the two main proposed enzyme orders derived from recent in vitro and in vivo work. One model emphasizes the following oxidative–reductive sequence: BaiB → BaiA2 → BaiCD → BaiF → BaiE → BaiN → BaiN → BaiA2. An alternative model, supported by other reconstitution and review studies, proposes the sequence BaiB → BaiA2 → BaiCD → BaiE → BaiF → BaiH → BaiCD → BaiA2, in which BaiH catalyzes the first reductive step and BaiCD and BaiA2 act twice, at the beginning and end of the redox cascade. In addition, downstream of LCA formation, the diagram notes microbiota derived LCA derivatives such as 3 oxoLCA, isoLCA, alloLCA, 3 oxoalloLCA and isoalloLCA, which are now established in human stool and are produced by combinations of bai encoded enzymes together with additional 5α/5β reductases and 3α/3β HSDHs encoded in distinct gene clusters; for these branches, the overall existence of the metabolites and enzyme activities is well supported, whereas the exact sequence of intermediates remains partially reconstructed. The diagram therefore captures the shared intermediates and directionality of 7α dehydroxylation, while indicating that the exact order and division of labor among bai and non bai enzymes, and their strain specific variants, remain active areas of research.

>> Metabolite and enzyme abbreviations and full names used:

• CA: Cholic acid

• CA-CoA: Cholyl-CoA

• 3-oxoCA-CoA: 3-oxo-CA-CoA

• 3-oxoΔ4-CA-CoA: 3-oxo-delta4-cholyl-CoA

• 3-oxoΔ4-CA: 3-oxo-delta4-CA

• 3-oxoΔ4,6-DCA: 3-oxo-delta4,6-DCA

• 3-oxoΔ4-DCA: 3-oxo-delta4-DCA

• 3-oxoDCA: 3-oxo-Deoxycholic acid

• DCA: Deoxycholic acid

• IsoDCA: Isodeoxycholic acid

• CDCA: Chenodeoxycholic Acid

• CDCA-CoA: Chenodeoxycholoyl-CoA

• 3-oxoCDCA-CoA: 3-oxo-chenodeoxycholyl-CoA

• 3-oxoΔ4-CDCA-CoA: 3-Oxo-delta4-chenodeoxycholyl-CoA

• 3-oxoΔ4-CDCA: 3-Oxo-4-cholenoic acid

• 3-oxoΔ4,6-LCA: 3-Oxo-4,6-choladienoic acid

• 3-oxoΔ4-LCA: 3-Oxo-4-cholenic acid

• 3-oxoLCA: Dehydrolithocholic Acid

• LCA: Lithocholic acid

• IsoLCA: Isolithocholic acid

• 3-oxoalloLCA: 3-Oxoallolithocholic acid

• isoalloLCA: Isoallolithocholic acid

• alloLCA: Allolithocholic acid

• BAIB_CLOSV: Bile acid-coenzyme A ligase

• BAIA1_CLOSV: 3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase

• BAICD_CLOSV: 3-oxocholoyl-CoA 4-desaturase

• BAIF_CLOSV: Bile acid CoA-transferase BaiF

• BAIE_CLOSV: Bile acid 7alpha-dehydratase

• BAIN_CLOS5: 3-dehydro-bile acid delta(4,6)-reductase

• BAIA2_CLOSV: 3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase 2

• BAIH_CLOSV: 7-beta-hydroxy-3-oxochol-24-oyl-CoA 4-desaturase

• 3alpha-HSDH: 3alpha,hydroxysteroid dehydrogenase

• 3beta-HSDH: 3beta,hydroxysteroid dehydrogenase

• 5AR: 5alpha-reductase