Melanchole: the dark side of bile acids and its cellular consequences
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The first bile acid, cholic acid, was discovered in 1848 from ox gallbladder, and the bile acid structure solved by Otto Wieland was recognized with the 1927 Nobel Prize in Chemistry.1 Primary bile acids are synthesized in the liver from cholesterol and conjugated to taurine or glycine for biliary secretion. Bile acid synthesis is catalyzed by approximately 17 enzymes via the classic or alternative pathways. The classic bile acid synthesis pathway is initiated by cholesterol 7α-hydroxylase (CYP7A1), followed by sterol 12α-hydroxylase (CYP8B1).
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Hydrophobic BAs are cytotoxic but at tolerated concentrations can promote proliferation, whereas hydrophilic BAs, particularly UDCA and MCA, are cytoprotective.
“Hydrophobic BAs are cytotoxic but at tolerated concentrations can promote proliferation,26,27,31 whereas hydrophilic BAs, particularly ursodeoxycholic acid and MCA, are cytoprotective.32,33”
From Constitutive Androstane Receptor Regulates Bile Acid Homeostasis and Metabolism During Liver Regeneration (2026) · cites this paper as [31]
The paper’s main text (page unavailable in our copy) says hydrophilic ursodeoxycholic acid protects against oxidative stress and cell death. It does not mention MCA or establish that MCA is cytoprotective. The proliferation clause has separate citations and is not assessed against this source. (LLM, conf=0.86)
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Research works printed but not linked: 18
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Cited by
Sorted by citations
Zhou, W., Chembazhi, U. V., Huang, J., Bangru, S., Dean, A. E., Asokakumar, A., Kalsotra, A., Rudnick, D. A., & Anakk, S. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101858
Self-citation
- Authors
- Zhou, W., & Anakk, S.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Anakk, Sayeepriyadarshini
- Venue
- Cellular and Molecular Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2022
- Volume
- 13
- Issue
- 5
- Pages
- 1474-1476
- ISSN
- 2352-345X (ISSN-L)
- PMC
- PMC9043294
- OpenAlex
- W4213244367
- Cited by
- 6
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 1 · 2022: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIDDK
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- bile acids, cholic acid, bile acid synthesis, CYP7A1, sterol 12alpha-hydroxylase, CYP8B1, taurine conjugation, glycine conjugation, bile acid metabolism, bile acid toxicity
- MeSH terms
- Bile Acids and Salts, Circadian Rhythm, Liver
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