Cholic acid-deoxycholic acid/ursocholic acid pathway: bile salt deconjugation, secondary bile acid synthesis, reconjugation and sulfation (Homo sapiens)
From WikiPathways
Description
This pathway illustrates how gut microbiota remodel cholic acid (CA)–based bile salts through deconjugation, secondary bile acid synthesis, reconjugation and sulfation along the enterohepatic circulation. It includes bacterial bile salt hydrolase–mediated deconjugation, 7-dehydroxylation and epimerization reactions that generate secondary bile acids such as deoxycholic acid, as well as hepatic reconjugation and sulfation steps that shape bile acid solubility, toxicity and signaling potential in both humans and mice.
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:
- GCA-7S: Glycocholic Acid-7-sulfate
- GCA: Glycocholic Acid
- TCA-7S: Taurocholic Acid-7-sulfate
- TCA: Taurocholic Acid
- CA: Cholic acid
- CA-7S: Cholic acid-7-sulfate
- Phe-chol: Phenylalanocholic acid
- Tyr-chol: Tyrosocholic acid
- Leu-chol: Leucocholic Acid
- 3-oxoCA: 3-oxocholic acid
- IsoCA: Isocholic acid
- 7-oxoDCA: 7-oxodeoxycholic acid
- UCA: Ursocholic acid
- TUCA: Tauroursocholic acid
- GUCA: Glycoursocholic acid
- 12-oxoCDCA: 12-oxochenodeoxycholic acid
- EpiCA: 12-epicholic acid
- DCA: Deoxycholic acid
- DCA-CoA: Deoxycholyl-CoA
- GDCA: Glycodeoxycholic acid
- GDCA-3S: Glycodeoxycholic acid-3-sulfate
- TDCA: Taurodeoxycholic acid
- TDCA-3S: taurodeoxycholic acid-3-sulfate
- 12-oxoLCA: 12-oxolithocholic acid
- EpiDCA: Epideoxycholic acid
- 3-oxoDCA: 3-oxodeoxycholic acid
- IsoDCA: Isodeoxycholic acid
- SULT2A1: Sulfotransferase 2A
- BAAT: Bile acid-CoA:amino acid N-acyltransferase
- SLC27A5: Bile acid-CoA synthethase
- 3AHDP_MEDG7: 3alpha,hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- 3BHDP_MEDG7: 3beta,hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- HDHA_ECOLI: 7alpha,hydroxysteroid dehydrogenase, Escherichia coli
- 3BHDP_MEDG7: 7beta,hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- HMPREF0262_01073: 12alpha,hydroxysteroid dehydrogenase, Clostridium sp.
- G594_RS0113520: 12beta,hydroxysteroid dehydrogenase: SDR family NAD(P)
-dependent oxidoreductase (Clostridium paraputrificum)
- CBH_CLOPE: Bile salt hydrolase/transferase, Clostridium perfringens
- 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
Please use the New WikiPathways
View approved pathways at the new wikipathways.org. This website will shutdown soon.Quality Tags
Ontology Terms
Saving...Bibliography
View all... |
- 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
- 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.
- 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
- Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS; ''Bile acids and the gut microbiome.''; Curr Opin Gastroenterol, 2014 PubMed Europe PMC Scholia
- Guzior DV, Quinn RA; ''Review: microbial transformations of human bile acids.''; Microbiome, 2021 PubMed Europe PMC Scholia
- 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
- 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
- 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
- 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
- Russell DW; ''The enzymes, regulation, and genetics of bile acid synthesis.''; Annu Rev Biochem, 2003 PubMed Europe PMC Scholia
- 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
- Falany CN, Johnson MR, Barnes S, Diasio RB; ''Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase.''; J Biol Chem, 1994 PubMed Europe PMC Scholia
- Dawson PA, Karpen SJ; ''''; , PubMed Europe PMC Scholia
- 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
- Takahashi S, Fukami T, Masuo Y, Brocker CN, Xie C, Krausz KW, Wolf CR, Henderson CJ, Gonzalez FJ; ''Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans.''; J Lipid Res, 2016 PubMed Europe PMC Scholia
- 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
- Alnouti Y; ''Bile Acid sulfation: a pathway of bile acid elimination and detoxification.''; Toxicol Sci, 2009 PubMed Europe PMC Scholia
- Ridlon JM, Kang DJ, Hylemon PB; ''Bile salt biotransformations by human intestinal bacteria.''; J Lipid Res, 2006 PubMed Europe PMC Scholia
- 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
- Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA, Christy MP, Bodai Z, Belda-Ferre P, Tripathi A, Chung LK, Downes M, Welch RD, Quinn M, Humphrey G, Panitchpakdi M, Weldon KC, Aksenov A, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa EA, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz JM, Meehan MJ, Gentry E, Arthur TD, Komor AC, Poulsen O, Boland BS, Chang JT, Sandborn WJ, Lim M, Garg N, Lumeng JC, Xavier RJ, Kazmierczak BI, Jain R, Egan M, Rhee KE, Ferguson D, Raffatellu M, Vlamakis H, Haddad GG, Siegel D, Huttenhower C, Mazmanian SK, Evans RM, Nizet V, Knight R, Dorrestein PC; ''Global chemical effects of the microbiome include new bile-acid conjugations.''; Nature, 2020 PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
| View all... |
Annotated Interactions
No annotated interactions
