Lithocholic acid, also known as 3α-hydroxy-5β-cholan-24-oic acid or LCA, is a

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary ...

that acts as a detergent to solubilize fats for absorption. Bacterial action in the colon produces LCA from

chenodeoxycholic acid Chenodeoxycholic acid (CDCA; also known as chenodesoxycholic acid, chenocholic acid and 3α,7α-dihydroxy-5β-cholan-24-oic acid) is a bile acid. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the ma ...

by reduction of the

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...

functional group at carbon-7 in the "B" ring of the

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

framework. It has been implicated in human and experimental animal carcinogenesis. Preliminary ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...

'' research suggests that LCA selectively kills

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump i ...

cells, while sparing normal neuronal cells and is cytotoxic to numerous other malignant cell types at physiologically relevant concentrations.

Dietary fiber Dietary fiber (in British English fibre) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition, and can be grouped generally by th ...

can bind to lithocholic acid and aid in its excretion in stool; as such, fiber can protect against colon cancer. LCA (and LCA acetate and LCA propionate) can activate the

vitamin D receptor The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer ...

without raising calcium levels as much as

vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 ...

itself. LCA binds with high affinity (20 μM) to the human membrane enzyme

NAPE-PLD NAPE-PLD may refer to: * N-acyl phosphatidylethanolamine-specific phospholipase D, an enzyme * N-acetylphosphatidylethanolamine-hydrolysing phospholipase D ''N''-acetylphosphatidylethanolamine-hydrolysing phospholipase D (EC 3.1.4.54, NAPE-PLD, a ...

, enhancing dimer assembly and enabling catalysis. NAPE-PLD catalyzes the release of

anandamide Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid r ...

and other

N-acylethanolamines An ''N''-acylethanolamine (NAE) is a type of fatty acid amide where one of several types of acyl groups is linked to the nitrogen atom of ethanolamine, and highly metabolic formed by intake of essential fatty acids through diet by 20:4, n-6 ...

(NAE) from the membrane precursor N-acyl-phosphatidylethanolamine(NAPE). NAPE-PLD facilitates crosstalk between

signals and lipid amide signals. LCA was also shown to have anti-aging effects in a yeast study.Arlia-Ciommo A, Leonov A, Mohammad K, Beach A, Richard VR, Bourque SD, Burstein MT, Goldberg AA, Kyryakov P, Gomez-Perez A, Koupaki O, Titorenko VI. Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions. ''Oncotarget''. 2018 Oct 9;9(79):34945-34971. A later study showed that the bile acid accumulates in the inner and outer mitochondrial membranes, altering the mitochondria's

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids incl ...

composition by promoting or inhibiting various enzymes.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.

References

{{DEFAULTSORT:Lithocholic Acid Bile acids Secondary alcohols Cholanes