ExplorEnz: EC 1.14.14.139

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1.14.14.139

Accepted name:

5β-cholestane-3α,7α-diol 12α-hydroxylase

Reaction:

(1) 5β-cholestane-3α,7α-diol + [reduced NADPH—hemoprotein reductase] + O₂ = 5β-cholestane-3α,7α,12α-triol + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 7α-hydroxycholest-4-en-3-one + [reduced NADPH—hemoprotein reductase] + O₂ = 7α,12α-dihydroxycholest-4-en-3-one + [oxidized NADPH—hemoprotein reductase] + H₂O
(3) chenodeoxycholate + [reduced NADPH—hemoprotein reductase] + O₂ = cholate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of cholesterol catabolism (rings A, B and C), click here

Glossary:

chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
cholate = 3α,7α-12α-trihydroxy-5β-cholan-24-oate

Other name(s):

5β-cholestane-3α,7α-diol 12α-monooxygenase; sterol 12α-hydroxylase (ambiguous); CYP8B1; cytochrome P450 8B1; 7α-hydroxycholest-4-en-3-one 12α-hydroxylase; 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; chenodeoxycholate 12α monooxygenase

Systematic name:

5β-cholestane-3α,7α-diol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in mammals. This is the key enzyme in the biosynthesis of the bile acid cholate. The enzyme can also hydroxylate 5β-cholestane-3α,7α-diol at the 25 and 26 position, but to a lesser extent [2].

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc, PDB

References:

1.	Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis and metabolism of bile acids. Catalytic properties of different forms of cytochrome P-450. J. Biol. Chem. 255 (1980) 1643–1649. [PMID: 6766451]
2.	Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis of bile acids. Cytochrome P-450 LM4 and 12α-hydroxylation of 5β-cholestane-3α,7α-diol. Eur. J. Biochem. 125 (1982) 423–429. [DOI] [PMID: 6811268]
3.	Ishida, H., Noshiro, M., Okuda, K. and Coon, M.J. Purification and characterization of 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase. J. Biol. Chem. 267 (1992) 21319–21323. [PMID: 1400444]
4.	Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K.I. and Björkhem, I. Molecular cloning and expression of rabbit sterol 12α-hydroxylase. J. Biol. Chem. 271 (1996) 32269–32275. [DOI] [PMID: 8943286]
5.	Lundell, K. and Wikvall, K. Gene structure of pig sterol 12α-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6α-hydroxylase (CYP4A21). Biochim. Biophys. Acta 1634 (2003) 86–96. [DOI] [PMID: 14643796]
6.	del Castillo-Olivares, A. and Gil, G. α1-Fetoprotein transcription factor is required for the expression of sterol 12α -hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription. J. Biol. Chem. 275 (2000) 17793–17799. [DOI] [PMID: 10747975]
7.	Yang, Y., Zhang, M., Eggertsen, G. and Chiang, J.Y. On the mechanism of bile acid inhibition of rat sterol 12α-hydroxylase gene (CYP8B1) transcription: roles of α-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha. Biochim. Biophys. Acta 1583 (2002) 63–73. [DOI] [PMID: 12069850]
8.	Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
9.	Fan, L., Joseph, J.F., Durairaj, P., Parr, M.K. and Bureik, M. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1. Biol. Chem. 400 (2019) 625–628. [DOI] [PMID: 30465713]

[EC 1.14.14.139 created 2005 as EC 1.14.13.96, transferred 2018 to EC 1.14.14.139 (EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, incorporated 2020) , modified 2020]