Lithocholic acid

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.^{[citation needed]}

It has been implicated in human and experimental animal carcinogenesis.^[2][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]

LCA binds with 20 μM affinity to the human membrane enzyme NAPE-PLD, enhancing dimer assembly and enabling catalysis. NAPE-PLD catalyzes the release of anandamide and other N-acylethanolamines (NAE) from the membrane precursor N-acylphosphatidylethanolamine (NAPE). NAPE-PLD facilitates crosstalk between bile acid signals and lipid amide signals.^[6][7][8]

LCA has been reported to have anti-aging effects in fruit flies, nematodes, and mice.^[9][10]

References

1. ^ Lithocholic acid at Sigma-Aldrich
2. ^ 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
3. ^ Zeng, H; Umar, S; Rust, B; Lazarova, D; Bordonaro, M (Mar 2019). "Secondary Bile Acids and Short Chain Fatty Acids in the Colon: A Focus on Colonic Microbiome, Cell Proliferation, Inflammation, and Cancer". Int J Mol Sci. 20 (5): 1214. doi:10.3390/ijms20051214. PMC 6429521. PMID 30862015
4. ^ 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
5. ^ 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. PMID 18180267
6. ^ Magotti P, Bauer I, Igarashi M, Babagoli M, Marotta R, Piomelli D, Garau G (Dec 2014). "Structure of Human N-Acylphosphatidylethanolamine-Hydrolyzing Phospholipase D: Regulation of Fatty Acid Ethanolamide Biosynthesis by Bile Acids". Structure. 23 (3): 598–604. doi:10.1016/j.str.2014.12.018. PMC 4351732. PMID 25684574
7. ^ Kostic M (2015). "Bile Acids as Enzyme Regulators". Chemistry & Biology. 22 (4): 427–428. doi:10.1016/j.chembiol.2015.04.007
8. ^ Margheritis E, Castellani B, Magotti P, Peruzzi S, Romeo E, Natali F, Mostarda S, Gioiello A, Piomelli D, Garau G (Oct 2016). "Bile Acid Recognition by NAPE-PLD.". ACS Chem Biol. 11 (10): 2908–2914. doi:10.1021/acschembio.6b00624. PMC 5074845. PMID 27571266
9. ^ Ledford, Heidi (2024). "Why eating less slows ageing: this molecule is key". Nature News. doi:10.1038/d41586-024-04220-5
10. ^ Qu, Qi; Chen, Yan; Wang, Yu; Long, Shating; Wang, Weiche; Yang, Heng-Ye; Li, Mengqi; Tian, Xiao; Wei, Xiaoyan; Liu, Yan-Hui; Xu, Shengrong; Zhang, Cixiong; Zhu, Mingxia; Lam, Sin Man; Wu, Jianfeng (2024-12-18). "Lithocholic acid phenocopies anti-ageing effects of calorie restriction". Nature. 643 (8070): 192–200. doi:10.1038/s41586-024-08329-5. ISSN 0028-0836. PMC 12222012. PMID 39695227