7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase

See also: CYP8B1

7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase
Identifiers
EC no.	1.14.14.139
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase (EC 1.14.14.139, previously EC 1.14.13.95) is an enzyme that catalyzes the chemical reaction:

7alpha-hydroxycholest-4-en-3-one + NADPH + H⁺ + O₂ ${\displaystyle \rightleftharpoons }$ 7alpha,12alpha-dihydroxycholest-4-en-3-one + NADP⁺ + H₂O

The 4 substrates of this enzyme are 7alpha-hydroxycholest-4-en-3-one (7 alpha-hydroxy-4-cholesten-3-one, NADPH, H⁺, and O₂. Its products are 7alpha,12alpha-dihydroxycholest-4-en-3-one, NADP⁺, and H₂O.

Since 2015, the enzyme has been classified with EC 1.14.14.139 with the systematic name of 5β-cholestan-3α,7α-diol 12α-hydroxylase. Other names that have been used include 7alpha-hydroxycholest-4-en-3-one,NADPH:oxygen oxidoreductase (12alpha-hydroxylating), 7alpha-hydroxy-4-cholesten-3-one 12alpha-monooxygenase, CYP12, sterol 12alpha-hydroxylase (ambiguous), and HCO 12alpha-hydroxylase.

This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O₂ as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O₂, with NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor. It was purified and characterized from rabbit liver microsomes in 1992^[1] and was cloned and sequenced in 1996.^[2] Its structure was 39% similar to human prostacyclin synthase (CYP8) and 31% similar to cholesterol 7 alpha-hydroxylase (CYP7).^[2]

This enzymatic activity is now known to be performed by the product of the CYP8B1 gene.^[3] This step leads to the formation of the bile acid cholic acid. Cholic acid is a 3,7,12 tri-hydroxy bile acid and is one of the major bile acids in humans and many other animals.^[4] Activity of this enzyme determines the balance between cholic and chenodeoxycholic acids in humans.^[4]

References

1. Ishida H, Noshiro M, Okuda K, Coon MJ (October 1992). "Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase". The Journal of Biological Chemistry. 267 (30): 21319–23. PMID 1400444.
2. Eggertsen G, Olin M, Andersson U, Ishida H, Kubota S, Hellman U, Okuda KI, Björkhem I (December 1996). "Molecular cloning and expression of rabbit sterol 12alpha-hydroxylase". The Journal of Biological Chemistry. 271 (50): 32269–75. doi:10.1074/jbc.271.50.32269. PMID 8943286.
3. "Entrez Gene: CYP8B1". Retrieved 9 April 2022.
4. Russell DW (2003). "The enzymes, regulation, and genetics of bile acid synthesis". Annual Review of Biochemistry. 72: 137–74. doi:10.1146/annurev.biochem.72.121801.161712. PMID 12543708.