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咨詢顧問3α,6?,7α,12α-tetrahydroxy bile acid (THBA)
THBA/3α,6?,7α,12α-tetrahydroxy bile acid
Bile acids (BAs) are naturally occurring physiological molecules, synthesized in the mammalian liver by peroxisomal enzymes as end products of cholesterol catabolism. They are crucial to the normal formation of bile flow, lipid digestion, and overall liver and metabolic health.
Having the structure of hydroxylated steroids, bile acids are the main detergents/emulsifying agents that prompt the digestion and absorption of fatty acids, lipid-soluble vitamins, and other fatty products in the intestines and prevent cholesterol precipitation in bile. They also act as signaling molecules in a range of biological pathways and have a role in energy, glucose, and lipid metabolism. In addition, BAs are involved in regulating their own biosynthesis and homeostasis through interaction with nuclear receptors.
3α,6?,7α,12α-tetrahydroxy bile acid (THBA) is a hydrophilic tetrahydroxy derivative of bile acids, synthesized from methyl cholate, that rarely appears or is present at minimal levels in healthy human adult organisms. However, THBA can be identified from healthy neonatal urine and human meconium through analysis by gas chromatography-mass spectrometry of fetal bile acids.
It has been found that THBA occurs in high levels in mice with genetically deleted canalicular bile salt export pump (BSEP), also called sister of P-glycoprotein (sPgp). Encoded by the ABCB11 gene, BSEP/sPgp is the major driving force for canalicular bile secretion. And normal bile formation together with its excretion are important functions of the liver.
Mutation of the ABCB11 gene causes significant BSEP deficiency, leading to decreased bile excretion which is the prime cause for intrahepatic cholestasis (accumulation of high concentration of toxic BAs) and liver damage - progressive familial intrahepatic cholestasis (PFIC). This condition is very common in children and presents clinically as infantile intrahepatic cholestasis.
The reason cholestasis is so harmful is that these accumulated BAs have a hydrophobic structure and hydrophobic groups define high cytotoxicity.
According to various studies, the BA pool in mice with target inactivation of BSEP/sPgp/ABCB11 gene contains a large amount of 3α,6?,7α,12α-tetrahydroxy bile acid (THBA) and the compound has been reported to have a positive impact on cholestatic conditions, resulting in nonprogressive cholestasis with low severity. This is because THBA is a result of one or more cytochrome P450 hydroxylation reactions, and polyhydroxylation increases the solubility and thus the secretion of toxic BAs. This series of hydroxylation processes is suggested to be the detoxification mechanism of THBA.
Moreover, THBA is believed to enhance bile flow, reduce liver inflammation, and prevent the formation of gallstones and hepatic tumors.
THBA is a considerable candidate for a therapeutic agent to treat cholestatic and other bile-associated diseases and conditions.
Avanti Polar Lipids can provide you with quality THBA to investigate its correlation with a range of cholestasis conditions and outcomes.
