Murine chenodeoxycholic acid - muricholic acid/ murideoxycholic acid pathway: bile salt deconjugation, secondary bile acid synthesis, reconjugation and sulfation (Mus musculus)
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Description
This pathway focuses on murine-specific transformations of CDCA-derived bile acids, in which hepatic CYP2C70 converts CDCA and UDCA into α and β muricholic acids (MCA), which are primary bile acids in mice and can be further epimerized (via 7 and 6 hydroxyl epimerization) and dehydroxylated by the gut microbiota to form secondary species such as murideoxycholic acid and ω MCA.
In mice, these MCA derivatives and their conjugated and sulfated forms are cycled through the enterohepatic circulation: gut bacteria deconjugate and desulfate muricholic and CDCA-derived bile salts, while hepatocytes reconjugate and resulfate them via SLC27A5, BAAT and sulfotransferase 2A, leading to a bile acid pool that is more enriched in muricholic acids than in humans.
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:
- αMCA: alpha-muricholic acid
- TαMCA: Tauro-alpha-muricholic acid
- GαMCA: Glyco-alpha-muricholic acid
- βMCA: beta-muricholic acid
- TβMCA: Tauro-beta-muricholic acid
- GβMCA: Glyco-beta-muricholic acid
- MDCA: Murideoxycholic acid
- 6-oxoLCA: 6-oxolithocholic acid
- HDCA: Hyodeoxycholic acid
- ωMCA: omega-muricholic acid
- GωMCA: Glyco-omega-muricholic acid
- TωMCA: Tauro-omega-muricholic acid
- CDCA: Chenodeoxycholic Acid
- UDCA: Ursodeoxycholic acid (UDCA)
- SULT2A1: Sulfotransferase 2A1
- BAAT: Bile acid-CoA:amino acid N-acyltransferase
- SLC27A5: Bile acid-CoA synthethase
- CYP2c70: Cytochrome P450 2C70: Bile acid 6beta-hydroxylase
- HDHA_ECOLI: 7alpha-hydroxysteroid dehydrogenase, Escherichia coli
- RUMGNA_02585: 7beta-hydroxysteroid dehydrogenase, Mediterraneibacter gnavus
- 6αHSDH: 6alpha-hydroxysteroid dehydrogenase
- 6βHSDH: 6beta-hydroxysteroid dehydrogenase
- CBH_BIFLN : Bile salt hydrolase/transferase, Bifidobacterium longum
- CBH_BIFL2 : Bile salt hydrolase/transferase, Bifidobacterium longum subsp. longum
- A0A8F5DVT9_9FIRM : Choloylglycine hydrolase, Christensenella minuta
- Secondary BA Synthesis(CDCA-LCA/UDCA): Pathway → Chenodeoxycholic acid – lithocholic acid/ursodeoxycholic acid pathway: bile salt deconjugation, secondary bile acid synthesis, reconjugation and sulfation
- 7α-dehydroxylation: Pathway → 7α-dehydroxylation of cholic acid and chenodeoxycholic acid by bai operon genes
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Ontology Terms
Saving...Bibliography
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- Zhuang T, Wang X, Wang Z, Gu L, Yue D, Li X, Yang L, Huang W, Ding L; ''Biological functions and pharmacological behaviors of bile acids in metabolic diseases.''; J Adv Res, 2025 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
- Guo GL, Chiang JYL; ''Is CYP2C70 the key to new mouse models to understand bile acids in humans?''; J Lipid Res, 2020 PubMed Europe PMC Scholia
- Honda A, Miyazaki T, Iwamoto J, Hirayama T, Morishita Y, Monma T, Ueda H, Mizuno S, Sugiyama F, Takahashi S, Ikegami T; ''Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition.''; J Lipid Res, 2020 PubMed Europe PMC Scholia
- Zhang Y, Limaye PB, Lehman-McKeeman LD, Klaassen CD; ''Dysfunction of organic anion transporting polypeptide 1a1 alters intestinal bacteria and bile acid metabolism in mice.''; PLoS One, 2012 PubMed Europe PMC Scholia
- Doden HL, Ridlon JM; ''Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega.''; Microorganisms, 2021 PubMed Europe PMC Scholia
- Paul A. Dawson.; ''7. 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
- Chiang JYL, Ferrell JM; ''Bile Acid Metabolism in Liver Pathobiology.''; Gene Expr, 2018 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
- Eyssen H, De Pauw G, Stragier J, Verhulst A; ''Cooperative formation of omega-muricholic acid by intestinal microorganisms.''; Appl Environ Microbiol, 1983 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
History
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| 6-oxoLCA | Metabolite | LMST04010146 (LIPID MAPS)  | |
| 6αHSDH | GeneProduct | CNIC-E001 (nan) | |
| 6βHSDH | GeneProduct | CNIC-E002 (nan) | |
| 7α-dehydroxylation | Pathway | WP5611 (WikiPathways) | |
| A0A8F5DVT9_9FIRM | GeneProduct | A0A8F5DVT9 (Uniprot-TrEMBL) | |
| BAAT | GeneProduct | Q91X34 (Uniprot-TrEMBL) | |
| CBH_BIFL2 | GeneProduct | P0DXD2 (Uniprot-TrEMBL) | |
| CBH_BIFLN | GeneProduct | Q9KK62 (Uniprot-TrEMBL) | |
| CDCA | Metabolite | LMST04010032 (LIPID MAPS) | |
| CYP2c70 | GeneProduct | Q91W64 (Uniprot-TrEMBL) | |
| GαMCA | Metabolite | 13955647 (PubChem-compound) | |
| GβMCA | Metabolite | 137333454 (PubChem-compound) | |
| GωMCA | Metabolite | CNIC-M001 (nan) | |
| HDCA | Metabolite | LMST04010024 (LIPID MAPS) | |
| MDCA | Metabolite | LMST04010025 (LIPID MAPS) | |
| SLC27A5 | GeneProduct | Q4LDG0 (Uniprot-TrEMBL) | |
| Secondary BA Synthesis(CDCA-LCA/UDCA) | Pathway | WP5612 (WikiPathways) | |
| TαMCA | Metabolite | LMST05040027 (LIPID MAPS) | |
| TβMCA | Metabolite | LMST05040012 (LIPID MAPS) | |
| TωMCA | Metabolite | LMST04010473 (LIPID MAPS) | |
| UDCA | Metabolite | LMST04010033 (LIPID MAPS) | |
| Unknown | |||
| αMCA | Metabolite | LMST04010066 (LIPID MAPS) | |
| βMCA | Metabolite | LMST04010067 (LIPID MAPS) | |
| ωMCA | Metabolite | LMST04010065 (LIPID MAPS) |
Annotated Interactions
No annotated interactions
