Chenodeoxycholic acid-lithocholic acid/ursodeoxycholic acid pathway: bile salt deconjugation, secondary bile acid synthesis, reconjugation and sulfation (Homo sapiens)

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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.

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Ontology Terms

 

Bibliography

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  1. Lee JY, Arai H, Nakamura Y, Fukiya S, Wada M, Yokota A; ''Contribution of the 7β-hydroxysteroid dehydrogenase from Ruminococcus gnavus N53 to ursodeoxycholic acid formation in the human colon.''; J Lipid Res, 2013 PubMed Europe PMC Scholia
  2. Fleishman JS, Kumar S; ''Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.''; Signal Transduct Target Ther, 2024 PubMed Europe PMC Scholia
  3. 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
  4. Di Ciaula A, Garruti G, Lunardi Baccetto R, Molina-Molina E, Bonfrate L, Wang DQ, Portincasa P; ''Bile Acid Physiology.''; Ann Hepatol, 2017 PubMed Europe PMC Scholia
  5. Russell DW; ''The enzymes, regulation, and genetics of bile acid synthesis.''; Annu Rev Biochem, 2003 PubMed Europe PMC Scholia
  6. Van Eldere J, Robben J, De Pauw G, Merckx R, Eyssen H; ''Isolation and identification of intestinal steroid-desulfating bacteria from rats and humans.''; Appl Environ Microbiol, 1988 PubMed Europe PMC Scholia
  7. Paul A. Dawson; ''Biochemistry of Lipids, Lipoproteins and Membranes (Sixth Edition), Chapter 12 - Bile Acid Metabolism''; https://doi.org/10.1016/B978-0-444-63438-2.00012-2, 2016
  8. Dawson PA, Karpen SJ; ''Intestinal transport and metabolism of bile acids.''; J Lipid Res, 2015 PubMed Europe PMC Scholia
  9. Cai J, Rimal B, Jiang C, Chiang JYL, Patterson AD; ''Bile acid metabolism and signaling, the microbiota, and metabolic disease.''; Pharmacol Ther, 2022 PubMed Europe PMC Scholia
  10. Doden HL, Wolf PG, Gaskins HR, Anantharaman K, Alves JMP, Ridlon JM; ''Completion of the gut microbial epi-bile acid pathway.''; Gut Microbes, 2021 PubMed Europe PMC Scholia
  11. Takahashi S, Fukami T, Masuo Y, Brocker CN, Xie C, Krausz KW, Wolf CR, Henderson CJ, Gonzalez FJ; ''Cyp2c70 is responsible for the speciesdifference in bile acid metabolism between mice and humans.''; J Lipid Res, 2016 PubMed Europe PMC Scholia
  12. 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
  13. Guzior DV, Okros M, Shivel M, Armwald B, Bridges C, Fu Y, Martin C, Schilmiller AL, Miller WM, Ziegler KM, Sims MD, Maddens ME, Graham SF, Hausinger RP, Quinn RA; ''Bile salt hydrolase acyltransferase activity expands bile acid diversity.''; Nature, 2024 PubMed Europe PMC Scholia
  14. Ridlon JM, Kang DJ, Hylemon PB; ''Bile salt biotransformations by human intestinal bacteria.''; J Lipid Res, 2006 PubMed Europe PMC Scholia
  15. Guzior DV, Quinn RA; ''Review: microbial transformations of human bile acids.''; Microbiome, 2021 PubMed Europe PMC Scholia
  16. Ito E, Inuki S, Izumi Y, Takahashi M, Dambayashi Y, Ciacchi L, Awad W, Takeyama A, Shibata K, Mori S, Mak JYW, Fairlie DP, Bamba T, Ishikawa E, Nagae M, Rossjohn J, Yamasaki S; ''Sulfated bile acid is a host-derived ligand for MAIT cells.''; Sci Immunol, 2024 PubMed Europe PMC Scholia
  17. Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS; ''Bile acids and the gut microbiome.''; Curr Opin Gastroenterol, 2014 PubMed Europe PMC Scholia
  18. Alnouti Y; ''Bile Acid sulfation: a pathway of bile acid elimination and detoxification.''; Toxicol Sci, 2009 PubMed Europe PMC Scholia
  19. 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
  20. Moon S, Smanski MJ; ''Biosynthesis of tauro-ursodeoxycholic acid (TUDCA) in Saccharomyces cerevisiae.''; Microb Cell Fact, 2025 PubMed Europe PMC Scholia
  21. 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
  22. Dawson PA, Setchell KDR; ''Will the real bile acid sulfotransferase please stand up? Identification of Sult2a8 as a major hepatic bile acid sulfonating enzyme in mice.''; J Lipid Res, 2017 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
142274view17:19, 24 December 2025JmrodriguezcOntology Term : 'primary bile acid biosynthetic pathway' added !
142273view17:19, 24 December 2025JmrodriguezcOntology Term : 'secondary bile acid biosynthetic pathway' added !
142272view17:19, 24 December 2025JmrodriguezcOntology Term : 'bile acid biosynthetic pathway' added !
142263view14:21, 24 December 2025JmrodriguezcCNIC-M/Exxx names fixed to correct formatting.
142254view11:45, 23 December 2025JmrodriguezcAdding recently found PubChem identifier for TUDCA-3S.
142248view11:56, 22 December 2025JmrodriguezcModified description
142229view12:28, 18 December 2025JmrodriguezcMinor adjustemnts in metabolites and enzymes positions, for clearer portrayal
142228view12:17, 18 December 2025JmrodriguezcAdded Murine CDCA-MCA/MDMCA pathway number (WP5613).
142226view10:56, 18 December 2025JmrodriguezcModified description
142221view10:23, 18 December 2025JmrodriguezcModified description
142220view10:23, 18 December 2025JmrodriguezcModified description
142219view10:22, 18 December 2025JmrodriguezcModified description
142213view18:26, 17 December 2025JmrodriguezcReplacing enzyme position next to reaction (instead of on top). Updating pathway title and pathway metabolite names to latest decisions.
142165view19:48, 7 December 2025JmrodriguezcAdjusted layout.

Added few references.

Added bile salt hydrolases.
142159view20:42, 6 December 2025JmrodriguezcNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
3-oxo-CDCAMetaboliteLMST04010161 (LIPID MAPS)
3-oxo-LCAMetaboliteLMST04010127 (LIPID MAPS)
3AHDP_MEDG7GeneProductA7B3K3 (Uniprot-TrEMBL)
3AHD_EGGLEGeneProductC8WMP0 (Uniprot-TrEMBL)
3BHD2_EGGLEGeneProductC8WGQ3 (Uniprot-TrEMBL)
3BHDP_MEDG7GeneProductA7AZH2 (Uniprot-TrEMBL)
7-dehydroxylationGeneProductWP5610 (WikiPathways)
7-oxo-LCAMetaboliteLMST04010150 (LIPID MAPS)
BAATGeneProductQ14032 (Uniprot-TrEMBL)
Bile acid sulfataseGeneProductCNIC-Enz001 (nan)
Bile salt hydrolaseGeneProductCNIC-Enz002 (nan)
CDCA-SMetaboliteLMST05020026 (LIPID MAPS)
CDCAMetaboliteLMST04010032 (LIPID MAPS)
CYP2c70GeneProductQ91W64 (Uniprot-TrEMBL)
GCDCA-SMetaboliteLMST05030005 (LIPID MAPS)
GCDCAMetaboliteLMST05030008 (LIPID MAPS)
GLCA-SMetaboliteLMST05030004 (LIPID MAPS)
GLCAMetaboliteLMST05030009 (LIPID MAPS)
GUDCAMetaboliteLMST05030016 (LIPID MAPS)
HDHA_BACFNGeneProductQ5LA59 (Uniprot-TrEMBL)
HDHA_ECOLIGeneProductP0AET8 (Uniprot-TrEMBL)
Iso-CDCAMetaboliteLMST04010034 (LIPID MAPS)
LCAMetaboliteLMST04010003 (LIPID MAPS)
Lithocholoyl-CoAMetabolite91828270 (PubChem-compound)
Murine CDCA–muricholic acid pathwayPathwayWPxxx (WikiPathways)
RUMGNA_02585GeneProductA7B4V1 (Uniprot-TrEMBL)
SLC27A5GeneProductQ9Y2P5 (Uniprot-TrEMBL)
SULT2A1GeneProductQ06520 (Uniprot-TrEMBL)
TCDCA-SMetaboliteLMST05020030 (LIPID MAPS)
TCDCAMetaboliteLMST05040005 (LIPID MAPS)
TLCA-SMetaboliteLMST05020003 (LIPID MAPS)
TLCAMetaboliteLMST05040003 (LIPID MAPS)
TUDCA-SMetaboliteCNIC-Metabo001 (nan)
TUDCAMetaboliteLMST05040015 (LIPID MAPS)
UDCAMetaboliteLMST04010033 (LIPID MAPS)
Ursodeoxychoyl-CoAMetabolite71448933 (PubChem-compound)
alpha-MCAMetaboliteLMST04010066 (LIPID MAPS)
beta-MCAMetaboliteLMST04010067 (LIPID MAPS)
iso-LCAMetaboliteLMST04010004 (LIPID MAPS)

Annotated Interactions

No annotated interactions

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