Lithocholic acid
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| Names | |
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| IUPAC name
(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-Hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid | |
| Other names
Lithocholate; Lithocolic acid; 3α-Hydroxy-5β-cholan-24-oic acid; 3α-Hydroxy-5β-cholanic acid; 5β-Cholan-24-oic acid-3α-ol | |
| Identifiers | |
3D model (JSmol) |
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.006.455 |
| EC Number | 207-099-1 |
PubChem CID |
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| RTECS number | FZ2275000 |
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| Properties | |
| C24H40O3 | |
| Molar mass | 376.57 g/mol |
| Melting point | 183 to 188 °C (361 to 370 °F; 456 to 461 K) |
| Hazards | |
| S-phrases (outdated) | S22 S24/25 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
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| Infobox references | |
Lithocholic acid, also known as 3α-hydroxy-5β-cholan-24-oic acid or LCA, is a bile acid that acts as a detergent to solubilize fats for absorption. Bacterial action in the colon produces LCA from chenodeoxycholic acid by reduction of the hydroxyl functional group at carbon-7 in the "B" ring of the steroid framework.
It has been implicated in human and experimental animal carcinogenesis.[2] Preliminary in vitro research suggests that LCA selectively kills neuroblastoma cells, while sparing normal neuronal cells and is cytotoxic to numerous other malignant cell types at physiologically relevant concentrations.[3]
Dietary fiber can bind to lithocholic acid and aid in its excretion in stool;[4] as such, fiber can protect against colon cancer.
LCA (and LCA acetate and LCA propionate) can activate the vitamin D receptor without raising calcium levels as much as vitamin D itself.[5]
Anti-aging effects
At a concentration of 50uL, exogenously added LCA was found to extend the mean and maximum chronological lifespan of yeast.[6] The bile acid accumulates in the inner and outer mitochondrial membranes, altering the mitochondria's lipid composition by promoting or inhibiting various enzymes.[7] The remodelling of the membranes changed the shape and number of mitochondria in the cell by (1) increasing their size, (2) decreasing their numbers, (3) decreasing the number crista extending from the IMM and (4) increasing the number disconnected crista in the mitochondrial matrix.[7]
In biology, structure is always correlated with functions. Therefore, various age-related mitochondrial processes are elevated: the membrane potential, the electron transport chain, ATP production, and reactive oxygen species levels.[7] This improves stress resistance in chronologically aged yeast cells, thereby promoting their survival. Furthermore, the changes to mitochondria size and number reduce mitochondrial fragmentation, thus reducing mitochondria-controlled apoptosis.[7]
References
- ↑ Lithocholic acid at Sigma-Aldrich
- ↑ Kozoni, V.; Tsioulias, G; Shiff, S; Rigas, B (2000). "The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: Differential effect on apoptosis in the presence of a colon carcinogen". Carcinogenesis. 21 (5): 999–1005. doi:10.1093/carcin/21.5.999. PMID 10783324.
- ↑ Goldberg, AA; Beach, A; Davies, GF; Harkness, TA; Leblanc, A; Titorenko, VI (2011). "Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells". Oncotarget. 2 (10): 761–82. doi:10.18632/oncotarget.338. PMC 3248158. PMID 21992775.
- ↑ Jenkins, DJ; Wolever, TM; Rao, AV; Hegele, RA; Mitchell, SJ; Ransom, TP; Boctor, DL; Spadafora, PJ; et al. (1993). "Effect on blood lipids of very high intakes of fiber in diets low in saturated fat and cholesterol". The New England Journal of Medicine. 329 (1): 21–6. doi:10.1056/NEJM199307013290104. PMID 8389421.
- ↑ Ishizawa, M.; Matsunawa, M.; Adachi, R.; Uno, S.; Ikeda, K.; Masuno, H.; Shimizu, M.; Iwasaki, K.-i.; et al. (2008). "Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia". The Journal of Lipid Research. 49 (4): 763–772. doi:10.1194/jlr.M700293-JLR200.
- ↑ Goldberg, AA; Richard, VR; Kyryakov, P; Bourque, SD; Beach, A; Burstein, MT; Glebov, A; Koupaki, O; et al. (2010). "Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes". Aging. 2 (7): 393–414. PMC 2933888. PMID 20622262.
- 1 2 3 4 Beach, A.; Richard, V.R.; Leonov, A.; Burstein, M.T.; Bourque, S.D.; Koupaki, O.; Juneau, M.; Feldman, R.; Iouk, T.; Titorenko, V.I. Mitochondrial membrane lipidome defines yeast longevity. Aging 2013, 5, 551–574.
Further reading
- Goldberg, AA; Richard, VR; Kyryakov, P; Bourque, SD; Beach, A; Burstein, MT; Glebov, A; Koupaki, O; et al. (2010). "Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes". Aging. 2 (7): 393–414. PMC 2933888. PMID 20622262.