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The initial step in the classical pathway of hepatic synthesis of bile acids is the enzymatic addition of a 7α hydroxyl group by cholesterol 7α-hydroxylase (CYP7A1) forming 7α-hydroxycholesterol. This is then metabolised to 7α-hydroxy-4-cholesten-3-one. There are multiple steps in bile acid synthesis requiring 14 enzymes in all. [3]
It is metabolized by the enzyme 7α-hydroxycholest-4-en-3-one 12α-hydroxylase to 7α,12α-dihydroxycholest-4-en-3-one and then to cholic acid, the major primary bile acid in humans. Alternatively, it can be converted into 5β-cholestane-3α,7α-diol and then to chenodeoxycholic acid, the other major primary bile acid in humans. [1]
104086 Ensembl ENSG00000135929 ENSMUSG00000026170 UniProt Q02318 Q9DBG1 RefSeq (mRNA) NM_000784 NM_024264 RefSeq (protein) NP_000775 NP_077226 Location (UCSC) Chr 2: 218.78 – 218.82 Mb Chr 1: 74.75 – 74.78 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in ...
Cholesterol 7 alpha-hydroxylase is the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7α-hydroxycholesterol. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. [8]
This is why chenodeoxycholic acid, and not cholic acid, can be used to treat gallstones (because decreasing bile acid synthesis would supersaturate the stones even more). [6] [7] Cholic acid and chenodeoxycholic acid are the most important human bile acids. Other species may synthesize different bile acids as their predominant primary bile ...
Because they act as gatekeepers for further bile acid modification, BSHs play an important role in the production of deconjugated bile acids that can be modified into secondary bile acids. [1] Secondary bile acids can influence innate immunity through their interactions with the bile acid receptors mentioned above, FXR and TGR-5. [ 19 ]
7α-Hydroxycholesterol is a precursor of bile acids, created by cholesterol 7α-hydroxylase (CYP7A1). Its formation is the rate-determining step in bile acid synthesis. [ 1 ]
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 main bile acids.