Lithocholic acid explained

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.[1] [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]

LCA binds with high affinity (20 μM) 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 was also shown to have anti-aging effects in a yeast study.[9] [10] A later study showed that the bile acid accumulates in the inner and outer mitochondrial membranes, altering the mitochondria's lipid composition by promoting or inhibiting various enzymes.[11]

Notes and References

  1. 10.1093/carcin/21.5.999 . 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 . 2000 . Kozoni . V. . Carcinogenesis . 21 . 5 . 999–1005 . 10783324 . Tsioulias . G . Shiff . S . Rigas . B.
  2. Zeng H, Umar S, Rust B, Lazarova D, Bordonaro M. 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. 2019 Mar 11;20(5):1214.
  3. 21992775 . 2011 . Goldberg . AA . Beach . A . Davies . GF . Harkness . TA . Leblanc . A . Titorenko . VI . Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells . 2 . 10 . 761–82 . Oncotarget . 3248158 . 10.18632/oncotarget.338.
  4. 8389421. 1993. Jenkins. DJ. Wolever. TM. Rao. AV. Hegele. RA. Mitchell. SJ. Ransom. TP. Boctor. DL. Spadafora. PJ. Jenkins. AL. Mehling. Christine. Relle. Lisa Katzman. Connelly. Philip W.. Story. Jon A.. Furumoto. Emily J.. Corey. Paul. Wursch. Pierre. Effect on blood lipids of very high intakes of fiber in diets low in saturated fat and cholesterol. 329. 1. 21–6. 10.1056/NEJM199307013290104. The New England Journal of Medicine. 8. free.
  5. 10.1194/jlr.M700293-JLR200 . 18180267 . Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia . 2008 . Ishizawa . M. . Matsunawa . M. . Adachi . R. . Uno . S. . Ikeda . K. . Masuno . H. . Shimizu . M. . Iwasaki . K.-i. . Yamada . S. . Makishima . M. . The Journal of Lipid Research . 49 . 4 . 763–772 . 8. free .
  6. Magotti P, Bauer I, Igarashi M, Babagoli M, Marotta R, Piomelli D, Garau G . Structure of Human N-Acylphosphatidylethanolamine-Hydrolyzing Phospholipase D: Regulation of Fatty Acid Ethanolamide Biosynthesis by Bile Acids . Structure . 23 . 3 . Dec 2014 . 10.1016/j.str.2014.12.018 . 25684574 . 598–604 . 4351732.
  7. Kostic M . Bile Acids as Enzyme Regulators . Chemistry & Biology . 22 . 4 . 2015 . 10.1016/j.chembiol.2015.04.007 . 427–428.
  8. Margheritis E, Castellani B, Magotti P, Peruzzi S, Romeo E, Natali F, Mostarda S, Gioiello A, Piomelli D, Garau G . Bile Acid Recognition by NAPE-PLD. . ACS Chem Biol . 11 . 10 . Oct 2016 . 10.1021/acschembio.6b00624 . 27571266 . 2908–2914 . 5074845.
  9. Richard. VR. Kyryakov. P. Bourque. SD. Beach. A. Burstein. MT. Glebov. A. Koupaki. O. Boukh-Viner. T. 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. 2933888. 20622262. Goldberg. AA. Gregg. C. Juneau. M. English. A. M.. Thomas. D. Y.. Titorenko. V. I.. 8. 10.18632/aging.100168.
  10. 10.18632/oncotarget.26188 . 30405886. Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions. 2018. Arlia-Ciommo. Anthony. Leonov. Anna. Mohammad. Karamat. Beach. Adam. Richard. Vincent R.. Bourque. Simon D.. Burstein. Michelle T.. Goldberg. Alexander A.. Kyryakov. Pavlo. Gomez-Perez. Alejandra. Koupaki. Olivia. Titorenko. Vladimir I.. Oncotarget. 9. 79. 34945–34971. 6201858.
  11. 10.18632/aging.100578 . Mitochondrial membrane lipidome defines yeast longevity . 2013 . Beach . Adam . Richard . Vincent R. . Leonov . Anna . Burstein . Michelle T. . Bourque . Simon D. . Koupaki . Olivia . Juneau . Mylène . Feldman . Rachel . Iouk . Tatiana . Titorenko . Vladimir I. . Aging . 5 . 7 . 551–574 . 23924582 . 3765583 .

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