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EC
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1.14.13.96
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| Transferred entry: | 5β-cholestane-3α,7α-diol 12α-hydroxylase. Now EC 1.14.14.139, 5β-cholestane-3α,7α-diol 12α-hydroxylase
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| [EC 1.14.13.96 created 2005, deleted 2018] |
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EC
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1.14.13.97
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| Transferred entry: | taurochenodeoxycholate 6α-hydroxylase. Now EC 1.14.14.57, taurochenodeoxycholate 6α-hydroxylase
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| [EC 1.14.13.97 created 2005, deleted 2018] |
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| EC |
1.14.14.57 |
| Accepted name: |
taurochenodeoxycholate 6α-hydroxylase |
| Reaction: |
(1) taurochenodeoxycholate + [reduced NADPH—hemoprotein reductase] + O2 = taurohyocholate + [oxidized NADPH—hemoprotein reductase] + H2O
(2) lithocholate + [reduced NADPH—hemoprotein reductase] + O2 = hyodeoxycholate + [oxidized NADPH—hemoprotein reductase] + H2O |
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For diagram of the biosynthesis of cholic-acid conjugates, click here |
| Glossary: |
taurochenodeoxycholic acid = N-(3α,7α-dihydroxy-5β-cholan-24-oyl)taurine
taurohyocholic acid = N-(3α,6α,7α-trihydroxy-5β-cholan-24-oyl)taurine
hyodeoxycholate = 3α,6α-dihydroxy-5β-cholan-24-oate
lithocholate = 3α-hydroxy-5β-cholan-24-oate |
| Other name(s): |
CYP3A4; CYP4A21; taurochenodeoxycholate 6α-monooxygenase |
| Systematic name: |
taurochenodeoxycholate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6α-hydroxylating) |
| Comments: |
A cytochrome P-450 (heme-thiolate) protein. Requires cytochrome b5 for maximal activity. Acts on taurochenodeoxycholate, taurodeoxycholate and less readily on lithocholate and chenodeoxycholate. In adult pig (Sus scrofa), hyocholic acid replaces cholic acid as a primary bile acid [5]. |
| Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 105669-85-0 |
| References: |
| 1. |
Araya, Z. and Wikvall, K. 6α-Hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes. Biochim. Biophys. Acta 1438 (1999) 47–54. [DOI] [PMID: 10216279] |
| 2. |
Araya, Z., Hellman, U. and Hansson, R. Characterisation of taurochenodeoxycholic acid 6α-hydroxylase from pig liver microsomes. Eur. J. Biochem. 231 (1995) 855–861. [DOI] [PMID: 7649186] |
| 3. |
Kramer, W., Sauber, K., Baringhaus, K.H., Kurz, M., Stengelin, S., Lange, G., Corsiero, D., Girbig, F., Konig, W. and Weyland, C. Identification of the bile acid-binding site of the ileal lipid-binding protein by photoaffinity labeling, matrix-assisted laser desorption ionization-mass spectrometry, and NMR structure. J. Biol. Chem. 276 (2001) 7291–7301. [DOI] [PMID: 11069906] |
| 4. |
Lundell, K., Hansson, R. and Wikvall, K. Cloning and expression of a pig liver taurochenodeoxycholic acid 6α-hydroxylase (CYP4A21): a novel member of the CYP4A subfamily. J. Biol. Chem. 276 (2001) 9606–9612. [DOI] [PMID: 11113117] |
| 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. |
Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708] |
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| [EC 1.14.14.57 created 2005 asEC 1.14.13.97, transferred 2018 to EC 1.14.14.57] |
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| EC |
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 |
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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] |
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| [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] |
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