一般描述 | Lithocholic acid(石胆酸) is a toxic secondary bile acid, causes intrahepatic cholestasis, has tumor-promoting activity, its toxic effect can be protected after it
activates the vitamin D receptor, PXR and FXR. |
生物活性/药理作用 | Lithocholic acid, also known as 3α-hydroxy-5β-cholan-24-oic acid or LCA, is a secondary bile acid. It is formed from chenodeoxycholate by bacterial action, and is usually conjugated
with glycine or taurine. It acts as a detergent to solubilize fats for
absorption and is itself absorbed. It is used as cholagogue and choleretic. Bile acids are steroid acids found predominantly in the bile of mammals. The
distinction between different bile acids is minute, and depends only on the presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and
transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids
recirculate through the liver, bile ducts, small intestine, and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH, and consequently require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are
essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e. g. membrane
disruption) and there are a plethora of mechanisms to limit their
accumulation in blood and tissues (PMID: 11316487, 16037564, 12576301, 11907135). When present in sufficiently high levels, lithocholic acid can act
as an oncometabolite. An oncometabolite is a compound that when present at chronically high levels promotes tumour growth and survival. Chronically high
levels of lithocholic acid are associated with several forms of cancer including colon cancer, pancreatic cancer, esophageal cancer, and many other
GI cancers. High bile acid levels lead to the generation of reactive oxygen
species and reactive nitrogen species, disruption of the cell membrane and mitochondria, induction of DNA damage, mutation and apoptosis, and the
development of reduced apoptosis capability upon chronic exposure (PMID: 24884764). Dietary fibre can bind to lithocholic acid and aid in its
excretion in stool. As such, fibre can protect against colon cancer. |
