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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]
This enzyme is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. This enzyme is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates.
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]
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]
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 ]
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 ...
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 ]
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 ...