Chenodeoxycholic acid-lithocholic acid/ursodeoxycholic acid pathway: bile salt deconjugation, secondary bile acid synthesis, reconjugation and sulfation (Mus musculus)
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Description
This pathway depicts how chenodeoxycholic acid (CDCA)–based bile salts are remodelled by gut microbiota and hepatocytes through deconjugation, secondary bile acid formation, reconjugation and sulfation.
In the distal small intestine and colon, bile salt hydrolases and bile acid sulfatases from gut bacteria deconjugate and desulfate CDCA-derived species, which can then undergo 7α dehydroxylation, oxidation and epimerization to generate lithocholic acid (LCA), ursodeoxycholic acid (UDCA) and related secondary bile acids; these products are partially reabsorbed and return to the liver, where bile acid CoA synthetase (SLC27A5), bile acid CoA:amino acid N acyltransferase (BAAT) and sulfotransferase 2A mediate reconjugation and resulfation, feeding back into the enterohepatic circulation.
To visually simplify the pathway diagram, the following convention was applied: (i) stacking multiple enzymes: when two or more enzymes catalyse the same conversion, their nodes are placed in a stacked position and their representative catalytic interactions may overlap, but they all possess a unique catalytic interaction to the corresponding conversion, computationally contributing effectively to the catalysed transformation.
>> Metabolite and enzyme abbreviations used with their full common names:
- GCDCA-7S: Glycochenodeoxycholic acid-7-sulfate
- TCDCA-7S: Taurochenodeoxycholic acid-7-sulfate
- GCDCA: Glycochenodeoxycholic acid
- TCDCA: Taurochenodeoxycholic acid
- CDCA: Chenodeoxycholic acid
- CDCA-7S: Chenodeoxycholic acid-7-sulfate
- LCA: Lithocholic acid
- LCA-CoA: Lithocholoyl-CoA
- GLCA: Glycolithocholic acid
- GLCA-3S: Glycolithocholic acid 3-sulfate
- TLCA: Taurolithocholic acid
- TLCA-3S: Taurolithocholic acid 3-sulfate
- 3-oxoLCA: 3-oxolithocholic acid
- isoLCA: Isolithocholic acid
- 3-oxo-CDCA: 3-Oxochenodeoxycholic acid
- IsoCDCA: Isochenodeoxycholic acid
- 7-oxoLCA: 7-oxolithocholic acid
- UDCA: Ursodeoxycholic acid
- UDCA-CoA: Ursodeoxycholoyl-CoA
- TUDCA: Tauroursodeoxycholic acid
- TUDCA-3S: Tauroursodeoxycholic acid-3-sulfate
- GUDCA: Glycoursodeoxycholic acid
- GUDCA-3S: Glycoursodeoxycholic acid 3-sulfate
- SULT2A1: Sulfotransferase 2A
- BAAT: Bile acid-CoA:amino acid N-acyltransferase
- SLC27A5: Bile acid-CoA synthethase
- 3AHDP_MEDG7: 3alpha-hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- 3AHD_EGGLE: 3alpha-hydroxysteroid dehydrogenase, Eggerthella lenta
- 3BHDP_MEDG7: 3beta-hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- 3BHD2_EGGLE: 3beta-hydroxysteroid dehydrogenase 2, Eggerthella lenta
- HDHA_ECOLI: 7alpha-hydroxysteroid dehydrogenase, Escherichia coli
- HDHA_BACFN: 7alpha-hydroxysteroid dehydrogenase, Bacteroides fragilis
- HSDHB_MEDG7: 7beta-hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- Bile acid sulfatase
- CBH_BIFLN : Bile salt hydrolase/transferase, Bifidobacterium longum
- CBH_BIFL2 : Bile salt hydrolase/transferase, Bifidobacterium longum subsp. longum
- A0A8F5DVT9_9FIRM : Choloylglycine hydrolase, Christensenella minuta
- 7α-dehydroxylation: Pathway → 7α-dehydroxylation of cholic acid and chenodeoxycholic acid by bai operon genes
- Murine CDCA–muricholic acid: Pathway → Murine chenodeoxycholic acid - muricholic acid/ murideoxycholic acid pathway: bile salt deconjugation, secondary bile acid synthesis, reconjugation and sulfation
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- Hadžić N, Bull LN, Clayton PT, Knisely AS; ''Diagnosis in bile acid-CoA: amino acid N-acyltransferase deficiency.''; World J Gastroenterol, 2012 PubMed Europe PMC Scholia
- Huang J, Bathena SP, Tong J, Roth M, Hagenbuch B, Alnouti Y; ''Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1).''; Xenobiotica, 2010 PubMed Europe PMC Scholia
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