As a naturally-occurring bile acid found in humans, vertebrates, and other mammals, chenodeoxycholic acid is critical to gallbladder function. In synthetic form, chenodeoxycholic acid is prescribed to treat bile acid malabsorption – a disease that results when bile acids are not sufficiently absorbed in the intestines.
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Table of Contents
What is Chenodeoxycholic Acid?
Chenodeoxycholic acid is a bile acid mainly found in the bile of vertebrates and mammals. Initially isolated from the bile of domestic geese, chenodeoxycholic acid is a type of carboxylic acid typically used to treat gallstones.
Along with cholic acid, chenodeoxycholic acid sodium salt is one of two primary human bile acids. Chenodeoxycholic acid contains two hydroxyl groups and is altered by adding another hydroxyl group to create cholic acid.
Chenodeoxycholic acid is produced as a white crystalline substance. It is not soluble in water, however can be dissolved in acetic acid and alcohol, and has a 165–167 °C melting point.
Chenodeoxycholic Acid Uses
Chenodeoxycholic acid supplements are used as a therapy to dissolve gallstones – small stones formed in the gallbladder that are made of cholesterol.
Chenodeoxycholic acid therapy (Treatment CTX) is used for patients with both small and large gallstones that are either reluctant or unable to undergo gallbladder surgery.
Chenodeoxycholic acid is used to treat cerebrotendineous xanthomatosis (CTX), thought to be a rare genetic disorder where an individual cannot produce bile. Cerebrotendineous xanthomatosis is believed to be caused by a deficiency of the mitochondrial enzyme sterol 27-hydroxylase due to an abnormality in the CYP27A1 gene. As a result, the lack of this enzyme prevents the conversion of cholesterol into chenodeoxycholic acid.
Other Conditions Treated With Chenodeoxycholic Acid
In addition to treating gallbladder stones and cerebrotendineous xanthomatosis ( Treatment CTX), chenodeoxycholic acid has been researched to treat constipation. Research into chenodeoxycholic acid suggests that the drug can improve bowel function and accelerate colonic transit.
Further applications of chenodeoxycholic acid include its use to treat Hepatitis C in combination with bezafibrate.
Chenodeoxycholic Acid Synthesis
The neural or classic pathway of the bile acid synthesis cascade is the most critical biosynthetic mechanism that produces over 90% of total bile acids in the body. This pathway ensures that both cholic acid and chenodeoxycholic acid are synthesized in nearly equal proportions. A key enzyme of this catabolic pathway is 7α-hydroxylase cholesterol (CYP 7A1). It determines the bile acid pool size and catalyzes the hydroxylation of cholesterol to 7α-hydroxycholesterol.
Oxidative shortening of the aliphatic side chain is preceded by modification of the steroid ring. 7α-hydroxycholesterol is converted by 3β-hydroxy–Δ5-C27-oxidoreductase (HSD3B7) to the 3–oxo–Δ4-form. This is followed by Δ4-3–oxosteroid−5β-reductase (AKR1D1), which reduces the Δ4 double bond. This leads to the formation of the 5β-hydrogen configuration.
The reduction of the 3–oxo group into the 3α-hydroxyl group by the 3α-hydroxysteroid dehydrogenase (AKR1C4) enzyme is the final step in the ring structure modification. 12α-hydroxylase (CYP 8B1) produces a CA when the hydroxylation reaction takes place in the C12 position with sterol. However, if hydroxylation does not occur in this position, chenodeoxycholic acid is produced.
The overall hydrophobicity of the pool of BAs is determined by the activity of the CYP8B1 enzyme. This is because cholic acid is more hydrophilic compared when compared to CDC. Following the modification of a ring structure, the carboxyl group is created at the C27 position by the mitochondrial sterol 27–hydroxylase (CYP 27A1). This forms C27 bile intermediates comprised of 3α, 7α-dihydroxy−5β-cholestanoic acid and 3α, 7α, 12α-trihydroxy−5β-cholestanoic acid.
The C27 bile intermediates are consequently activated into the corresponding coenzyme A ester. Two enzymes involved in this process are located in the endoplasmic reticulum: a very long chain acyl–CoA synthetase and acid–CoA synthetase (BACS). Following this process, activated CoA C27 bile esters are moved in peroxisome membrane protein with the use of peroxisomal membrane protein 70 (PMP 70, ABCD3). This occurs before trimming the side chain, chiral carbon C25 racemizes from the R– to S– configuration with the use of α-methylacyl CoA racemase . Then, the side chain can be shortened by peroxisomal β-oxidation.
In the peroxisomes, acyl CoA oxidase 2 oxidizes (D / T) HC–CoA, forming a double bond at position C24. The double bond is hydroxylated into 24–hydroxy–(D / T) HC–CoA, and this process is proceeded by the dehydrogenation into the 24–keto (D / T) HC–CoA, and D–bifunctional protein catalyzes both reactions. Propionyl CoA, CDCA–CoA, or CA–CoA are produced by the thiolytic separation of the resulting ketone using a sterol carrier protein X (SCPx) (Li et al., 2013).
Chenodeoxycholic Acid vs. Other Acids
Chenodeoxycholic Acid and Ursodeoxycholic Acid
Ursodeoxycholic acid, along with chenodeoxycholic acid, dissolve gallstones in the human body.
Chenodeoxycholic Acid and Glycochenodeoxycholic Acid
Glycochenodeoxycholic acid is a bile salt created in the liver from chenodeoxycholic acid and glycine.
Chenodeoxycholic Acid and Lithocholic Acid
Lithocholic acid is a secondary bile acid created by bacterial 7-dehydroxylation of chenodeoxycholic acid and ursodeoxycholic acid.
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Chenodeoxycholic Acid FAQ
Chenodeoxycholic acid is a bile acid used to treat gallstones. This type of acid is predominantly found in the bile of vertebrates and mammals. Chenodeoxycholic acid is a type of carboxylic acid, and was initially isolated from the bile of domestic geese.
Chenodeoxycholic acid was first approved in 1983 and sold under the brand name Chenix to treat radiolucent stones in the gallbladder. Alternative names or brands of chenodeoxycholic acid include Chenodiol, Chenofalk, LB-101 – Leadiant Biosciences, LB101, and Xenbilox.
Chenodeoxycholic acid is synthesized from cholesterol in hepatocytes – chief functional cells of the liver. The formation rate of primary bile acids is determined by the activity of microsomal cholesterol 7 hydroxylase – and enzyme inhibited by bile acids.
Chenodeoxycholic acid is not recommended for use in pregnant women or women of childbearing potential that do not use contraception. Experts recommend advising women that the drug can potentially harm the fetus and to avoid becoming pregnant if taking the medication.