The Enzyme Database

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EC 1.1.1.34     
Accepted name: hydroxymethylglutaryl-CoA reductase (NADPH)
Reaction: (R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
For diagram of mevalonate biosynthesis, click here
Other name(s): hydroxymethylglutaryl coenzyme A reductase (reduced nicotinamide adenine dinucleotide phosphate); 3-hydroxy-3-methylglutaryl-CoA reductase (ambiguous); β-hydroxy-β-methylglutaryl coenzyme A reductase (ambiguous); hydroxymethylglutaryl CoA reductase (NADPH); S-3-hydroxy-3-methylglutaryl-CoA reductase (ambiguous); NADPH-hydroxymethylglutaryl-CoA reductase; HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating-CoA); 3-hydroxy-3-methylglutaryl CoA reductase (NADPH); hydroxymethylglutaryl-CoA reductase (NADPH2)
Systematic name: (R)-mevalonate:NADP+ oxidoreductase (CoA-acylating)
Comments: The enzyme is inactivated by EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} and reactivated by EC 3.1.3.47 {[hydroxymethylglutaryl-CoA reductase (NADPH)]-phosphatase}.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-35-7
References:
1.  Bucher, N.L.R., Overath, P. and Lynen, F. β-Hydroxy-β-methylglutaryl coenzyme A reductase, cleavage and condensing enzymes in relation to cholesterol formation in rat liver. Biochim. Biophys. Acta 40 (1960) 491–501. [PMID: 13805544]
2.  Durr, I.F. and Rudney, H. The reduction of β-hydroxy-β-methylglutaryl coenzyme A to mevalonic acid. J. Biol. Chem. 235 (1960) 2572–2578. [PMID: 13818862]
3.  Kawachi, T. and Rudney, H. Solubilization and purification of β-hydroxy-β-methylglutaryl coenzyme A reductase from rat liver. Biochemistry 9 (1970) 1700. [PMID: 4985697]
[EC 1.1.1.34 created 1961]
 
 
EC 1.1.1.52     
Accepted name: 3α-hydroxycholanate dehydrogenase (NAD+)
Reaction: lithocholate + NAD+ = 3-oxo-5β-cholan-24-oate + NADH + H+
For diagram of cholesterol catabolism (rings A, B and C), click here
Glossary: lithocholate = 3α-hydroxy-5β-cholan-24-oate
Other name(s): α-hydroxy-cholanate dehydrogenase; lithocholate:NAD+ oxidoreductase; 3α-hydroxycholanate dehydrogenase
Systematic name: lithocholate:NAD+ 3-oxidoreductase
Comments: Also acts on other 3α-hydroxysteroids with an acidic side-chain. cf. EC 1.1.1.392, 3α-hydroxycholanate dehydrogenase (NADP+).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9028-57-3
References:
1.  Hayaishi, O., Saito, Y., Jakoby, W.B. and Stohlman, E.F. Reversible enzymatic oxidation of bile acids. Arch. Biochem. Biophys. 56 (1955) 554–555. [DOI] [PMID: 14377608]
[EC 1.1.1.52 created 1961, modified 1976, modified 2016]
 
 
EC 1.1.1.62     
Accepted name: 17β-estradiol 17-dehydrogenase
Reaction: 17β-estradiol + NAD(P)+ = estrone + NAD(P)H + H+
Other name(s): 20α-hydroxysteroid dehydrogenase; 17β,20α-hydroxysteroid dehydrogenase; 17β-estradiol dehydrogenase; estradiol dehydrogenase; estrogen 17-oxidoreductase; 17β-HSD; HSD17B7
Systematic name: 17β-estradiol:NAD(P)+ 17-oxidoreductase
Comments: The enzyme oxidizes or reduces the hydroxy/keto group on C17 of estrogens and androgens in mammals and regulates the biological potency of these steroids. The mammalian enzyme is bifunctional and also catalyses EC 1.1.1.270, 3β-hydroxysteroid 3-dehydrogenase [3]. The enzyme also acts on (S)-20-hydroxypregn-4-en-3-one and related compounds, oxidizing the (S)-20-group, but unlike EC 1.1.1.149, 20α-hydroxysteroid dehydrogenase, it is Si-specific with respect to NAD(P)+.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9028-61-9
References:
1.  Kautsky, M.P. and Hagerman, D.D. 17β-Estradiol dehydrogenase of ovine ovaries. J. Biol. Chem. 245 (1970) 1978–1984. [PMID: 4314937]
2.  Langer, L.J., Alexander, J.A. and Engel, L.L. Human placental estradiol-17β dehydrogenase. II. Kinetics and substrate specificities. J. Biol. Chem. 234 (1959) 2609–2614. [PMID: 14413943]
3.  Marijanovic, Z., Laubner, D., Moller, G., Gege, C., Husen, B., Adamski, J. and Breitling, R. Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis. Mol. Endocrinol. 17 (2003) 1715–1725. [DOI] [PMID: 12829805]
[EC 1.1.1.62 created 1965, modified 1983, modified 1986, modified 2012]
 
 
EC 1.1.1.145     
Accepted name: 3β-hydroxy-Δ5-steroid dehydrogenase
Reaction: a 3β-hydroxy-Δ5-steroid + NAD+ = a 3-oxo-Δ5-steroid + NADH + H+
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): progesterone reductase; Δ5-3β-hydroxysteroid dehydrogenase; 3β-hydroxy-5-ene steroid dehydrogenase; 3β-hydroxy steroid dehydrogenase/isomerase; 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase; 3β-hydroxy-Δ5-C27-steroid oxidoreductase; 3β-hydroxy-5-ene-steroid oxidoreductase; steroid-Δ5-3β-ol dehydrogenase; 3β-HSDH; 5-ene-3-β-hydroxysteroid dehydrogenase; 3β-hydroxy-5-ene-steroid dehydrogenase
Systematic name: 3β-hydroxy-Δ5-steroid:NAD+ 3-oxidoreductase
Comments: This activity is found in several bifunctional enzymes that catalyse the oxidative conversion of Δ5-3-hydroxy steroids to a Δ4-3-oxo configuration. This conversion is carried out in two separate, sequential reactions; in the first reaction, which requires NAD+, the enzyme catalyses the dehydrogenation of the 3β-hydroxy steroid to a 3-oxo intermediate. In the second reaction the reduced coenzyme, which remains attached to the enzyme, activates the isomerization of the Δ5 form to a Δ4 form (cf. EC 5.3.3.1, steroid Δ-isomerase). Substrates include dehydroepiandrosterone (which is converted into androst-5-ene-3,17-dione), pregnenolone (converted to progesterone) and cholest-5-en-3-one, an intermediate of cholesterol degradation.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9044-85-3
References:
1.  Cheatum, S.G. and Warren, J.C. Purification and properties of 3-β-hydroxysteroid dehydrogenase and Δ-5-3-ketosteroid isomerase from bovine corpora lutea. Biochim. Biophys. Acta 122 (1966) 1–13. [PMID: 4226148]
2.  Koritz, S.B. The conversion of prepnenolone to progesterone by small particle from rat adrenal. Biochemistry 3 (1964) 1098–1102. [PMID: 14220672]
3.  Neville, A.M., Orr, J.C. and Engel, L.L. Δ5-3β-Hydroxy steroid dehydrogenase activities of bovine adrenal cortex. Biochem. J. 107 (1968) 20.
[EC 1.1.1.145 created 1972]
 
 
EC 1.1.1.170     
Accepted name: 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating)
Reaction: a 3β-hydroxysteroid-4α-carboxylate + NAD(P)+ = a 3-oxosteroid + CO2 + NAD(P)H
For diagram of sterol ring A modification, click here
Other name(s): 3β-hydroxy-4β-methylcholestenecarboxylate 3-dehydrogenase (decarboxylating); 3β-hydroxy-4β-methylcholestenoate dehydrogenase; sterol 4α-carboxylic decarboxylase; sterol-4α-carboxylate 3-dehydrogenase (decarboxylating) (ambiguous); ERG26 (gene name); NSDHL (gene name)
Systematic name: 3β-hydroxysteroid-4α-carboxylate:NAD(P)+ 3-oxidoreductase (decarboxylating)
Comments: The enzyme participates in the biosynthesis of several important sterols such as ergosterol and cholesterol. It is part of a three enzyme system that removes methyl groups from the C-4 position of steroid molecules. The first enzyme, EC 1.14.18.9, 4α-methylsterol monooxygenase, catalyses three successive oxidations of the methyl group, resulting in a carboxyl group; the second enzyme, EC 1.1.1.170, catalyses an oxidative decarboxylation that results in a reduction of the 3β-hydroxy group at the C-3 carbon to an oxo group; and the last enzyme, EC 1.1.1.270, 3β-hydroxysteroid 3-dehydrogenase, reduces the 3-oxo group back to a 3β-hydroxyl. If a second methyl group remains at the C-4 position, this enzyme also catalyses its epimerization from 4β to 4α orientation, so it could serve as a substrate for a second round of demethylation. cf. EC 1.1.1.418, plant 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 71822-23-6
References:
1.  Sharpless, K.B., Snyder, T.E., Spencer, T.A., Maheshwari, K.K. and Nelson, J.A. Biological demethylation of 4,4-dimethyl sterols, Evidence for enzymic epimerization of the 4β-methyl group prior to its oxidative removal. J. Am. Chem. Soc. 91 (1969) 3394–3396. [PMID: 5791927]
2.  Rahimtula, A.D. and Gaylor, J.L. Partial purification of a microsomal sterol 4α-carboxylic acid decarboxylase. J. Biol. Chem. 247 (1972) 9–15. [PMID: 4401584]
3.  Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624–10629. [PMID: 7430141]
4.  Gachotte, D., Barbuch, R., Gaylor, J., Nickel, E. and Bard, M. Characterization of the Saccharomyces cerevisiae ERG26 gene encoding the C-3 sterol dehydrogenase (C-4 decarboxylase) involved in sterol biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 13794–13799. [DOI] [PMID: 9811880]
5.  Caldas, H. and Herman, G.E. NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets. Hum. Mol. Genet. 12 (2003) 2981–2991. [DOI] [PMID: 14506130]
[EC 1.1.1.170 created 1978, modified 2002, modified 2012, modified 2019]
 
 
EC 1.1.1.181     
Accepted name: cholest-5-ene-3β,7α-diol 3β-dehydrogenase
Reaction: cholest-5-ene-3β,7α-diol + NAD+ = 7α-hydroxycholest-4-en-3-one + NADH + H+
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): 3β-hydroxy-Δ5-C27-steroid oxidoreductase (ambiguous)
Systematic name: cholest-5-ene-3β,7α-diol:NAD+ 3-oxidoreductase
Comments: Highly specific for 3β,7α-dihydroxy-C27-steroids with Δ5-double bond.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 56626-16-5
References:
1.  Wikvall, K. Purification and properties of a 3β-hydroxy-Δ5-C27-steroid oxidoreductase from rabbit liver microsomes. J. Biol. Chem. 256 (1981) 3376–3380. [PMID: 6937465]
2.  Schwarz, M., Wright, A.C., Davis, D.L., Nazer, H., Bjorkhem, I. and Russell, D.W. The bile acid synthetic gene 3β-hydroxy-Δ5-C27-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis. J. Clin. Invest. 106 (2000) 1175–1184. [PMID: 11067870]
[EC 1.1.1.181 created 1983]
 
 
EC 1.1.1.270     
Accepted name: 3β-hydroxysteroid 3-dehydrogenase
Reaction: a 3β-hydroxysteroid + NADP+ = a 3-oxosteroid + NADPH + H+
For diagram of sterol ring A modification, click here
Other name(s): 3-keto-steroid reductase; 3-KSR; HSD17B7 (gene name); ERG27 (gene name)
Systematic name: 3β-hydroxysteroid:NADP+ 3-oxidoreductase
Comments: The enzyme acts on multiple 3β-hydroxysteroids. Participates in the biosynthesis of zemosterol and cholesterol, where it catalyses the reaction in the opposite direction to that shown. The mammalian enzyme is bifunctional and also catalyses EC 1.1.1.62, 17β-estradiol 17-dehydrogenase [4].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 42616-29-5
References:
1.  Swindell, A.C. and Gaylor, J.L. Investigation of the component reactions of oxidative sterol demethylation. Formation and metabolism of 3-ketosteroid intermediates. J. Biol. Chem. 243 (1968) 5546–5555. [PMID: 4387005]
2.  Billheimer, J.T., Alcorn, M. and Gaylor, J.L. Solubilization and partial purification of a microsomal 3-ketosteroid reductase of cholesterol biosynthesis. Purification and properties of 3β-hydroxysteroid dehydrogenase and Δ5-3-ketosteroid isomerase from bovine corpora lutea. Arch. Biochem. Biophys. 211 (1981) 430–438. [DOI] [PMID: 6946726]
3.  Gachotte, D., Sen, S.E., Eckstein, J., Barbuch, R., Krieger, M., Ray, B.D. and Bard, M. Characterization of the Saccharomyces cerevisiae ERG27 gene encoding the 3-keto reductase involved in C-4 sterol demethylation. Proc. Natl. Acad. Sci. USA 96 (1999) 12655–12660. [DOI] [PMID: 10535978]
4.  Marijanovic, Z., Laubner, D., Moller, G., Gege, C., Husen, B., Adamski, J. and Breitling, R. Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis. Mol. Endocrinol. 17 (2003) 1715–1725. [DOI] [PMID: 12829805]
[EC 1.1.1.270 created 2002, modified 2012]
 
 
EC 1.1.3.6     
Accepted name: cholesterol oxidase
Reaction: cholesterol + O2 = cholest-5-en-3-one + H2O2
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): cholesterol- O2 oxidoreductase; 3β-hydroxy steroid oxidoreductase; 3β-hydroxysteroid:oxygen oxidoreductase
Systematic name: cholesterol:oxygen oxidoreductase
Comments: Contains FAD. Cholesterol oxidases are secreted bacterial bifunctional enzymes that catalyse the first two steps in the degradation of cholesterol. The enzyme catalyses the oxidation of the 3β-hydroxyl group to a keto group, and the isomerization of the double bond in the oxidized steroid ring system from the Δ5 position to Δ6 position (cf. EC 5.3.3.1, steroid Δ-isomerase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-76-6
References:
1.  Richmond, W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin. Chem. 19 (1973) 1350–1356. [PMID: 4757363]
2.  Stadtman, T.C., Cherkes, A. and Anfinsen, C.B. Studies on the microbiological degradation of cholesterol. J. Biol. Chem. 206 (1954) 511–523. [PMID: 13143010]
3.  MacLachlan, J., Wotherspoon, A.T., Ansell, R.O. and Brooks, C.J. Cholesterol oxidase: sources, physical properties and analytical applications. J. Steroid Biochem. Mol. Biol. 72 (2000) 169–195. [DOI] [PMID: 10822008]
4.  Vrielink, A. Cholesterol oxidase: structure and function. Subcell. Biochem. 51 (2010) 137–158. [DOI] [PMID: 20213543]
[EC 1.1.3.6 created 1961, modified 1982, modified 2012]
 
 
EC 1.3.1.3     
Accepted name: Δ4-3-oxosteroid 5β-reductase
Reaction: (1) 5β-cholestan-3-one + NADP+ = cholest-4-en-3-one + NADPH + H+
(2) 17,21-dihydroxy-5β-pregnane-3,11,20-trione + NADP+ = cortisone + NADPH + H+
For diagram of cholesterol catabolism (rings A, B and C), click here
Glossary: cortisone = 17,21-dihydroxypregn-4-ene-3,11,20-trione
Other name(s): 3-oxo-Δ4-steroid 5β-reductase; 5β-reductase; androstenedione 5β-reductase; cholestenone 5β-reductase; cortisone 5β-reductase; cortisone β-reductase; cortisone Δ4-5β-reductase; steroid 5β-reductase; testosterone 5β-reductase; Δ4-3-ketosteroid 5β-reductase; Δ4-5β-reductase; Δ4-hydrogenase; 4,5β-dihydrocortisone:NADP+ Δ4-oxidoreductase; 3-oxo-5β-steroid:NADP+ Δ4-oxidoreductase
Systematic name: 5β-cholestan-3-one:NADP+ 4,5-oxidoreductase
Comments: The enzyme from human efficiently catalyses the reduction of progesterone, androstenedione, 17α-hydroxyprogesterone and testosterone to 5β-reduced metabolites; it can also act on aldosterone, corticosterone and cortisol, but to a lesser extent [8]. The bile acid intermediates 7α,12α-dihydroxy-4-cholesten-3-one and 7α-hydroxy-4-cholesten-3-one can also act as substrates [9].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-08-7
References:
1.  Forchielli, E. and Dorfman, R.I. Separation of Δ4-5α- and Δ4-5β-hydrogenases from rat liver homogenates. J. Biol. Chem. 223 (1956) 443–448. [PMID: 13376613]
2.  Brown-Grant, K., Forchielli, E. and Dorfman, R.I. The Δ4-hydrogenases of guinea pig adrenal gland. J. Biol. Chem. 235 (1960) 1317–1320. [PMID: 13805063]
3.  Levy, H.R. and Talalay, P. Enzymatic introduction of double bonds into steroid ring A. J. Am. Chem. Soc. 79 (1957) 2658–2659.
4.  Tomkins, G.M. The enzymatic reduction of Δ4-3-ketosteroids. J. Biol. Chem. 225 (1957) 13–24. [PMID: 13416214]
5.  Sugimoto, Y., Yoshida, M. and Tamaoki, B. Purification of 5β-reductase from hepatic cytosol fraction of chicken. J. Steroid Biochem. 37 (1990) 717–724. [PMID: 2278855]
6.  Furuebisu, M., Deguchi, S. and Okuda, K. Identification of cortisone 5β-reductase as Δ4-3-ketosteroid 5β-reductase. Biochim. Biophys. Acta 912 (1987) 110–114. [DOI] [PMID: 3828348]
7.  Okuda, A. and Okuda, K. Purification and characterization of Δ4-3-ketosteroid 5β-reductase. J. Biol. Chem. 259 (1984) 7519–7524. [PMID: 6736016]
8.  Charbonneau, A. and The, V.L. Genomic organization of a human 5β-reductase and its pseudogene and substrate selectivity of the expressed enzyme. Biochim. Biophys. Acta 1517 (2001) 228–235. [DOI] [PMID: 11342103]
9.  Kondo, K.H., Kai, M.H., Setoguchi, Y., Eggertsen, G., Sjöblom, P., Setoguchi, T., Okuda, K.I. and Björkhem, I. Cloning and expression of cDNA of human Δ4-3-oxosteroid 5β-reductase and substrate specificity of the expressed enzyme. Eur. J. Biochem. 219 (1994) 357–363. [PMID: 7508385]
[EC 1.3.1.3 created 1961 (EC 1.3.1.23 created 1972, incorporated 2005), modified 2005]
 
 
EC 1.3.1.21     
Accepted name: 7-dehydrocholesterol reductase
Reaction: cholesterol + NADP+ = cholesta-5,7-dien-3β-ol + NADPH + H+
For diagram of sterol ring b, c, D modification, click here
Other name(s): DHCR7 (gene name); 7-DHC reductase; 7-dehydrocholesterol dehydrogenase/cholesterol oxidase; Δ7-sterol reductase
Systematic name: cholesterol:NADP+ Δ7-oxidoreductase
Comments: The enzyme is part of the cholesterol biosynthesis pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9080-21-1
References:
1.  Dempsey, M.E., Seaton, J.D., Schroepfer, G.J. and Trockman, R.W. The intermediary role of Δ5,7-cholestadien-3β-ol in cholesterol biosynthesis. J. Biol. Chem. 239 (1964) 1381–1387. [PMID: 14189869]
2.  Moebius, F.F., Fitzky, B.U., Lee, J.N., Paik, Y.K. and Glossmann, H. Molecular cloning and expression of the human Δ7-sterol reductase. Proc. Natl. Acad. Sci. USA 95 (1998) 1899–1902. [DOI] [PMID: 9465114]
[EC 1.3.1.21 created 1972, modified 2013]
 
 
EC 1.3.1.70     
Accepted name: Δ14-sterol reductase
Reaction: 4,4-dimethyl-5α-cholesta-8,24-dien-3β-ol + NADP+ = 4,4-dimethyl-5α-cholesta-8,14,24-trien-3β-ol + NADPH + H+
For diagram of the modification of sterol rings B, C and D, click here
Systematic name: 4,4-dimethyl-5α-cholesta-8,24-dien-3β-ol:NADP+ Δ14-oxidoreductase
Comments: This enzyme acts on a range of steroids with a 14(15)-double bond.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 69403-07-2
References:
1.  Bottema, C.K. and Parks, L.W. Δ14-Sterol reductase in Saccharomyces cerevisiae. Biochim. Biophys. Acta 531 (1978) 301–307. [DOI] [PMID: 32908]
2.  Paik, Y.K., Trzaskos, J.M., Shafice, A. and Gaylor, J.L. Microsomal enzymes of cholesterol biosynthesis from lanosterol. Characterization, solubilization, and partial purification of NADPH-dependent Δ8,14-steroid 14-reductase. J. Biol. Chem. 259 (1984) 13413–13423. [PMID: 6444198]
[EC 1.3.1.70 created 2001]
 
 
EC 1.3.1.72     
Accepted name: Δ24-sterol reductase
Reaction: 5α-cholest-7-en-3β-ol + NADP+ = 5α-cholesta-7,24-dien-3β-ol + NADPH + H+
For diagram of sterol-sidechain modification, click here
Glossary: desmosterol = cholesta-5,24-dien-3β-ol
lanosterol = 4,4,14-trimethyl-5α-cholesta-8,24-dien-3β-ol
zymostrol = 5α-cholesta-8,24-dien-3β-ol
Other name(s): lanosterol Δ24-reductase
Systematic name: sterol:NADP+ Δ24-oxidoreductase
Comments: Acts on a range of steroids with a 24(25)-double bond, including lanosterol, desmosterol and zymosterol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9033-57-2
References:
1.  Bae, S.H. and Paik, Y.K. Cholesterol biosynthesis from lanosterol: development of a novel assay method and characterization of rat liver microsomal lanosterol Δ24-reductase. Biochem. J. 326 (1997) 609–616. [PMID: 9291139]
[EC 1.3.1.72 created 2001]
 
 
EC 1.14.1.9      
Deleted entry:  cholesterol 20-hydroxylase
[EC 1.14.1.9 created 1965, deleted 1972]
 
 
EC 1.14.13.15      
Transferred entry: cholestanetriol 26-monooxygenase. Now EC 1.14.15.15, cholestanetriol 26-monooxygenase.
[EC 1.14.13.15 created 1976, modified 2005, modified 2012, deleted 2016]
 
 
EC 1.14.13.17      
Transferred entry: cholesterol 7α-monooxygenase. Now EC 1.14.14.23, cholesterol 7α-monooxygenase
[EC 1.14.13.17 created 1976, deleted 2016]
 
 
EC 1.14.13.60      
Transferred entry: 27-hydroxycholesterol 7α-monooxygenase. Now included with EC 1.14.13.100, 25-hydroxycholesterol 7α-hydroxylase
[EC 1.14.13.60 created 1999, deleted 2013]
 
 
EC 1.14.13.70      
Transferred entry: sterol 14α-demethylase. Now EC 1.14.14.154, sterol 14α-demethylase
[EC 1.14.13.70 created 2001, modified 2013, deleted 2018]
 
 
EC 1.14.13.72      
Transferred entry: methylsterol monooxygenase. Now classified as EC 1.14.18.9, methylsterol monooxygenase
[EC 1.14.13.72 created 1972 as EC 1.14.99.16, transferred 2002 to EC 1.14.13.72, deleted 2017]
 
 
EC 1.14.13.95      
Transferred entry: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase. Now EC 1.14.18.8, 7α-hydroxycholest-4-en-3-one 12α-hydroxylase
[EC 1.14.13.95 created 2005, deleted 2015]
 
 
EC 1.14.13.96      
Transferred entry: 5β-cholestane-3α,7α-diol 12α-hydroxylase. Now EC 1.14.14.139, 5β-cholestane-3α,7α-diol 12α-hydroxylase
[EC 1.14.13.96 created 2005, deleted 2018]
 
 
EC 1.14.13.98      
Transferred entry: cholesterol 24-hydroxylase. Now EC 1.14.14.25, cholesterol 24-hydroxylase
[EC 1.14.13.98 created 2005, deleted 2016]
 
 
EC 1.14.13.99      
Transferred entry: 24-hydroxycholesterol 7α-hydroxylase. Now EC 1.14.14.26, 24-hydroxycholesterol 7α-hydroxylase
[EC 1.14.13.99 created 2005, deleted 2016]
 
 
EC 1.14.13.100      
Transferred entry: 25/26-hydroxycholesterol 7α-hydroxylase. Now classified as EC 1.14.14.29, 25/26-hydroxycholesterol 7α-hydroxylase
[EC 1.14.13.100 created 2005, modified 2013 (EC 1.14.13.60 created 1999, incorporated 2013), deleted 2016]
 
 
EC 1.14.13.132      
Transferred entry: squalene monooxygenase. Now EC 1.14.14.17, squalene monooxygenase
[EC 1.14.13.132 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7, transferred 2011 to EC 1.14.13.132, deleted 2015]
 
 
EC 1.14.13.141      
Transferred entry: cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]. Now EC 1.14.15.29, cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]..
[EC 1.14.13.141 created 2012, modified 2016, deleted 2018]
 
 
EC 1.14.13.142      
Transferred entry: 3-ketosteroid 9α-monooxygenase. Now EC 1.14.15.30, 3-ketosteroid 9α-monooxygenase
[EC 1.14.13.142 created 2012, deleted 2018]
 
 
EC 1.14.13.221      
Transferred entry: cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]. Now EC 1.14.15.28, cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]
[EC 1.14.13.221 created 2016, deleted 2018]
 
 
EC 1.14.14.12     
Accepted name: 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione monooxygenase
Reaction: 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + FMNH2 + O2 = 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + FMN + H2O
Other name(s): HsaA
Systematic name: 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione,FMNH2:oxygen oxidoreductase
Comments: This bacterial enzyme participates in the degradation of several steroids, including cholesterol and testosterone. It can use either FADH or FMNH2 as flavin cofactor. The enzyme forms a two-component system with a reductase (HsaB) that utilizes NADH to reduce the flavin, which is then transferred to the oxygenase subunit.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, UM-BBD
References:
1.  Dresen, C., Lin, L.Y., D'Angelo, I., Tocheva, E.I., Strynadka, N. and Eltis, L.D. A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism. J. Biol. Chem. 285 (2010) 22264–22275. [DOI] [PMID: 20448045]
[EC 1.14.14.12 created 2011]
 
 
EC 1.14.14.17     
Accepted name: squalene monooxygenase
Reaction: squalene + [reduced NADPH—hemoprotein reductase] + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of α-onocerin biosynthesis, click here and for diagram of triterpenoid biosynthesis, click here
Other name(s): squalene epoxidase; squalene-2,3-epoxide cyclase; squalene 2,3-oxidocyclase; squalene hydroxylase; squalene oxydocyclase; squalene-2,3-epoxidase
Systematic name: squalene,NADPH—hemoprotein:oxygen oxidoreductase (2,3-epoxidizing)
Comments: A flavoprotein (FAD). This enzyme, together with EC 5.4.99.7, lanosterol synthase, was formerly known as squalene oxidocyclase. The electron donor is EC 1.6.2.4, NADPH—hemoprotein reductase [5,7].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9029-62-3
References:
1.  Corey, E.J., Russey, W.E. and Ortiz de Montellano, P.R. 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene. J. Am. Chem. Soc. 88 (1966) 4750–4751. [PMID: 5918046]
2.  Tchen, T.T. and Bloch, K. On the conversion of squalene to lanosterol in vitro. J. Biol. Chem. 226 (1957) 921–930. [PMID: 13438881]
3.  van Tamelen, E.E., Willett, J.D., Clayton, R.B. and Lord, K.E. Enzymic conversion of squalene 2,3-oxide to lanosterol and cholesterol. J. Am. Chem. Soc. 88 (1966) 4752–4754. [PMID: 5918048]
4.  Yamamoto, S. and Bloch, K. Studies on squalene epoxidase of rat liver. J. Biol. Chem. 245 (1970) 1670–1674. [PMID: 5438357]
5.  Ono, T. and Bloch, K. Solubilization and partial characterization of rat liver squalene epoxidase. J. Biol. Chem. 250 (1975) 1571–1579. [PMID: 234459]
6.  Satoh, T., Horie, M., Watanabe, H., Tsuchiya, Y. and Kamei, T. Enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae. Biol. Pharm. Bull. 16 (1993) 349–352. [PMID: 8358382]
7.  Chugh, A., Ray, A. and Gupta, J.B. Squalene epoxidase as hypocholesterolemic drug target revisited. Prog. Lipid Res. 42 (2003) 37–50. [DOI] [PMID: 12467639]
8.  He, F., Zhu, Y., He, M. and Zhang, Y. Molecular cloning and characterization of the gene encoding squalene epoxidase in Panax notoginseng. DNA Seq 19 (2008) 270–273. [DOI] [PMID: 17852349]
[EC 1.14.14.17 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7, transferred 2011 to EC 1.14.13.132, transferred 2015 to EC 1.14.14.17]
 
 
EC 1.14.14.23     
Accepted name: cholesterol 7α-monooxygenase
Reaction: cholesterol + [reduced NADPH—hemoprotein reductase] + O2 = 7α-hydroxycholesterol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): cholesterol 7α-hydroxylase; CYP7A1 (gene name)
Systematic name: cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (7α-hydroxylating)
Comments: A P-450 heme-thiolate liver protein that catalyses the first step in the biosynthesis of bile acids. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9037-53-0
References:
1.  Mitton, J.R., Scholan, N.A. and Boyd, G.S. The oxidation of cholesterol in rat liver sub-cellular particles. The cholesterol-7α-hydroxylase enzyme system. Eur. J. Biochem. 20 (1971) 569–579. [DOI] [PMID: 4397276]
2.  Boyd, G.S., Grimwade, A.M. and Lawson, M.E. Studies on rat-liver microsomal cholesterol 7α-hydroxylase. Eur. J. Biochem. 37 (1973) 334–340. [DOI] [PMID: 4147676]
3.  Ogishima, T., Deguchi, S. and Okuda, K. Purification and characterization of cholesterol 7α-hydroxylase from rat liver microsomes. J. Biol. Chem. 262 (1987) 7646–7650. [PMID: 3584134]
4.  Nguyen, L.B., Shefer, S., Salen, G., Ness, G., Tanaka, R.D., Packin, V., Thomas, P., Shore, V. and Batta, A. Purification of cholesterol 7 α-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies. J. Biol. Chem. 265 (1990) 4541–4546. [PMID: 2106520]
5.  Nguyen, L.B., Shefer, S., Salen, G., Chiang, J.Y. and Patel, M. Cholesterol 7α-hydroxylase activities from human and rat liver are modulated in vitro posttranslationally by phosphorylation/dephosphorylation. Hepatology 24 (1996) 1468–1474. [DOI] [PMID: 8938182]
[EC 1.14.14.23 created 1976 as EC 1.14.13.17, transferred 2016 to EC 1.14.14.23]
 
 
EC 1.14.14.25     
Accepted name: cholesterol 24-hydroxylase
Reaction: cholesterol + [reduced NADPH—hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3β,24-diol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of cholic acid biosynthesis (sidechain), click here
Glossary: cholesterol = cholest-5-en-3β-ol
(24S)-24-hydroxycholesterol = (24S)-cholest-5-ene-3β,24-diol
Other name(s): cholesterol 24-monooxygenase; CYP46; CYP46A1; cholesterol 24S-hydroxylase; cytochrome P450 46A1
Systematic name: cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)
Comments: A P-450 heme-thiolate protein. The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol [2]. This reaction is the first step in the enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood—brain barrier whereas cholesterol cannot [3]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 50812-30-1, 213327-78-7
References:
1.  Lund, E.G., Guileyardo, J.M. and Russell, D.W. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc. Natl. Acad. Sci. USA 96 (1999) 7238–7243. [DOI] [PMID: 10377398]
2.  Bogdanovic, N., Bretillon, L., Lund, E.G., Diczfalusy, U., Lannfelt, L., Winblad, B., Russell, D.W. and Björkhem, I. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci. Lett. 314 (2001) 45–48. [DOI] [PMID: 11698143]
3.  Mast, N., Norcross, R., Andersson, U., Shou, M., Nakayama, K., Bjorkhem, I. and Pikuleva, I.A. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry 42 (2003) 14284–14292. [DOI] [PMID: 14640697]
4.  Lund, E.G., Xie, C., Kotti, T., Turley, S.D., Dietschy, J.M. and Russell, D.W. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J. Biol. Chem. 278 (2003) 22980–22988. [DOI] [PMID: 12686551]
5.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.14.25 created 2005 as EC 1.14.13.98, transferred 2016 to EC 1.14.14.25]
 
 
EC 1.14.14.26     
Accepted name: 24-hydroxycholesterol 7α-hydroxylase
Reaction: (24S)-cholest-5-ene-3β,24-diol + [reduced NADPH—hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3β,7α,24-triol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of cholesterol catabolism (rings a, B and c), click here
Glossary: (24S)-cholest-5-ene-3β,24-diol = (24S)-24-hydroxycholesterol
Other name(s): 24-hydroxycholesterol 7α-monooxygenase; CYP39A1; CYP39A1 oxysterol 7α-hydroxylase
Systematic name: (24S)-cholest-5-ene-3β,24-diol,NADPH—hemoprotein reductase:oxygen oxidoreductase (7α-hydroxylating)
Comments: A P-450 heme-thiolate protein that is found in liver microsomes and in ciliary non-pigmented epithelium [2]. The enzyme is specific for (24S)-cholest-5-ene-3β,24-diol, which is formed mostly in the brain by EC 1.14.14.25, cholesterol 24-hydroxylase. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 288309-90-0
References:
1.  Li-Hawkins, J., Lund, E.G., Bronson, A.D. and Russell, D.W. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem. 275 (2000) 16543–16549. [DOI] [PMID: 10748047]
2.  Ikeda, H., Ueda, M., Ikeda, M., Kobayashi, H. and Honda, Y. Oxysterol 7alpha-hydroxylase (CYP39A1) in the ciliary nonpigmented epithelium of bovine eye. Lab. Invest. 83 (2003) 349–355. [PMID: 12649335]
3.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.14.26 created 2005 as EC 1.14.13.99, transferred 2016 to EC 1.14.14.26]
 
 
EC 1.14.14.29     
Accepted name: 25/26-hydroxycholesterol 7α-hydroxylase
Reaction: (1) cholest-5-ene-3β,25-diol + [reduced NADPH—hemoprotein reductase] + O2 = cholest-5-ene-3β,7α,25-triol + [oxidized NADPH—hemoprotein reductase] + H2O
(2) (25R)-cholest-5-ene-3β,26-diol + [reduced NADPH—hemoprotein reductase] + O2 = (25R)-cholest-5-ene-3β,7α,26-triol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of cholesterol catabolism (rings a, B and c), click here
Other name(s): 25-hydroxycholesterol 7α-monooxygenase; CYP7B1; CYP7B1 oxysterol 7α-hydroxylase; 27-hydroxycholesterol 7-monooxygenase; 27-hydroxycholesterol 7α-hydroxylase; cholest-5-ene-3β,25-diol,NADPH:oxygen oxidoreductase (7α-hydroxylating); 25-hydroxycholesterol 7α-hydroxylase
Systematic name: cholest-5-ene-3β,25/26-diol,[NADPH—hemoprotein reductase]:oxygen oxidoreductase (7α-hydroxylating)
Comments: A P-450 (heme-thiolate) protein. Unlike EC 1.14.14.26, 24-hydroxycholesterol 7α-monooxygenase, which is specific for its oxysterol substrate, this enzyme can also metabolize the oxysterols 24,25-epoxycholesterol, 22-hydroxycholesterol and 24-hydroxycholesterol, but to a lesser extent [2]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 149316-80-3
References:
1.  Kumiko, O.M., Budai, K. and Javitt, N.B. Cholesterol and 27-hydroxycholesterol 7α-hydroxylation: evidence for two different enzymes. J. Lipid Res. 34 (1993) 581–588. [PMID: 8496664]
2.  Toll, A., Wikvall, K., Sudjana-Sugiaman, E., Kondo, K.H. and Björkhem, I. 7α hydroxylation of 25-hydroxycholesterol in liver microsomes. Evidence that the enzyme involved is different from cholesterol 7α-hydroxylase. Eur. J. Biochem. 224 (1994) 309–316. [DOI] [PMID: 7925343]
3.  Li-Hawkins, J., Lund, E.G., Bronson, A.D. and Russell, D.W. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem. 275 (2000) 16543–16549. [DOI] [PMID: 10748047]
4.  Ren, S., Marques, D., Redford, K., Hylemon, P.B., Gil, G., Vlahcevic, Z.R. and Pandak, W.M. Regulation of oxysterol 7α-hydroxylase (CYP7B1) in the rat. Metabolism 52 (2003) 636–642. [DOI] [PMID: 12759897]
5.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.14.29 created 2005 as EC 1.14.13.100, modified 2013 (EC 1.14.13.60 created 1999, incorporated 2013), transferred 2016 to EC 1.14.14.29]
 
 
EC 1.14.14.46     
Accepted name: pimeloyl-[acyl-carrier protein] synthase
Reaction: a long-chain acyl-[acyl-carrier protein] + 2 reduced flavodoxin + 3 O2 = pimeloyl-[acyl-carrier protein] + an n-alkanal + 2 oxidized flavodoxin + 3 H2O (overall reaction)
(1a) a long-chain acyl-[acyl-carrier protein] + reduced flavodoxin + O2 = a (7S)-7-hydroxy-long-chain-acyl-[acyl-carrier protein] + oxidized flavodoxin + H2O
(1b) a (7S)-7-hydroxy-long-chain-acyl-[acyl-carrier protein] + reduced flavodoxin + O2 = a (7R,8R)-7,8-dihydroxy-long-chain-acyl-[acyl-carrier protein] + oxidized flavodoxin + H2O
(1c) a (7R,8R)-7,8-dihydroxy-long-chain-acyl-[acyl-carrier protein] + reduced flavodoxin + O2 = a 7-oxoheptanoyl-[acyl-carrier protein] + an n-alkanal + oxidized flavodoxin + 2 H2O
(1d) a 7-oxoheptanoyl-[acyl-carrier protein] + oxidized flavodoxin + H2O = a pimeloyl-[acyl-carrier protein] + reduced flavodoxin + H+
Glossary: a long-chain acyl-[acyl-carrier protein] = an acyl-[acyl-carrier protein] thioester where the acyl chain contains 13 to 22 carbon atoms.
palmitoyl-[acyl-carrier protein] = hexadecanoyl-[acyl-carrier protein]
pimeloyl-[acyl-carrier protein] = 6-carboxyhexanoyl-[acyl-carrier protein]
Other name(s): bioI (gene name); P450BioI; CYP107H1
Systematic name: acyl-[acyl-carrier protein],reduced-flavodoxin:oxygen oxidoreductase (pimeloyl-[acyl-carrier protein] forming)
Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme catalyses an oxidative C-C bond cleavage of long-chain acyl-[acyl-carrier protein]s of various lengths to generate pimeloyl-[acyl-carrier protein], an intermediate in the biosynthesis of biotin. The preferred substrate of the enzyme from the bacterium Bacillus subtilis is palmitoyl-[acyl-carrier protein] which then gives heptanal as the alkanal. The mechanism is similar to EC 1.14.15.6, cholesterol monooxygenase (side-chain-cleaving), followed by a hydroxylation step, which may occur spontaneously [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Stok, J.E. and De Voss, J. Expression, purification, and characterization of BioI: a carbon-carbon bond cleaving cytochrome P450 involved in biotin biosynthesis in Bacillus subtilis. Arch. Biochem. Biophys. 384 (2000) 351–360. [DOI] [PMID: 11368323]
2.  Cryle, M.J. and De Voss, J.J. Carbon-carbon bond cleavage by cytochrome p450(BioI)(CYP107H1). Chem. Commun. (Camb.) (2004) 86–87. [DOI] [PMID: 14737344]
3.  Cryle, M.J. and Schlichting, I. Structural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450(BioI) ACP complex. Proc. Natl. Acad. Sci. USA 105 (2008) 15696–15701. [DOI] [PMID: 18838690]
4.  Cryle, M.J. Selectivity in a barren landscape: the P450(BioI)-ACP complex. Biochem. Soc. Trans. 38 (2010) 934–939. [DOI] [PMID: 20658980]
[EC 1.14.14.46 created 2013 as EC 1.14.15.12, transferred 2017 to EC 1.14.14.46]
 
 
EC 1.14.14.139     
Accepted name: 5β-cholestane-3α,7α-diol 12α-hydroxylase
Reaction: 5β-cholestane-3α,7α-diol + [reduced NADPH—hemoprotein reductase] + O2 = 5β-cholestane-3α,7α,12α-triol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): 5β-cholestane-3α,7α-diol 12α-monooxygenase; sterol 12α-hydroxylase (ambiguous); CYP8B1; cytochrome P450 8B1
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 cholic acid (3α,7α,12α-trihydroxy-5β-cholanoic acid). The activity of this enzyme determines the biosynthetic ratio between cholic acid and chenodeoxycholic acid [3]. The enzyme can also hydroxylate the substrate at the 25 and 26 position, but to a lesser extent [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  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]
2.  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]
3.  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]
4.  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]
5.  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]
6.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.14.139 created 2005 as EC 1.14.13.96, transferred 2018 to EC 1.14.14.139]
 
 
EC 1.14.14.154     
Accepted name: sterol 14α-demethylase
Reaction: a 14α-methylsteroid + 3 [reduced NADPH—hemoprotein reductase] + 3 O2 = a Δ14-steroid + formate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H2O (overall reaction)
(1a) a 14α-methylsteroid + [reduced NADPH—hemoprotein reductase] + O2 = a 14α-hydroxymethylsteroid + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) a 14α-hydroxysteroid + [reduced NADPH—hemoprotein reductase] + O2 = a 14α-formylsteroid + [oxidized NADPH—hemoprotein reductase] + 2 H2O
(1c) a 14α-formylsteroid + [reduced NADPH—hemoprotein reductase] + O2 = a Δ14-steroid + formate + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of sterol ring B, C, D modification, click here
Glossary: obtusifoliol = 4α,14α-dimethyl-5α-ergosta-8,24(28)-dien-3β-ol or 4α,14α-dimethyl-24-methylene-5α-cholesta-8-en-3β-ol
Other name(s): obtusufoliol 14-demethylase; lanosterol 14-demethylase; lanosterol 14α-demethylase; sterol 14-demethylase; CYP51 (gene name); ERG11 (gene name)
Systematic name: sterol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (14-methyl cleaving)
Comments: This cytochrome P-450 (heme-thiolate) enzyme acts on a range of steroids with a 14α-methyl group, such as obtusifoliol and lanosterol. The enzyme catalyses a hydroxylation and a reduction of the 14α-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 60063-87-8
References:
1.  Alexander, K., Akhtar, M., Boar, R.B., McGhie, J.F. and Barton, D.H.R. The removal of the 32-carbon atom as formic acid in cholesterol biosynthesis. J. Chem. Soc. Chem. Commun. (1972) 383–385.
2.  Yoshida, Y. and Aoyama, Y. Yeast cytochrome P-450 catalyzing lanosterol 14 α-demethylation. I. Purification and spectral properties. J. Biol. Chem. 259 (1984) 1655–1660. [PMID: 6363414]
3.  Aoyama, Y., Yoshida, Y. and Sato, R. Yeast cytochrome P-450 catalyzing lanosterol 14 α-demethylation. II. Lanosterol metabolism by purified P-45014DM and by intact microsomes. J. Biol. Chem. 259 (1984) 1661–1666. [PMID: 6420412]
4.  Aoyama, Y. and Yoshida, Y. Different substrate specificities of lanosterol 14α-demethylase (P-45014DM) of Saccharomyces cerevisiae and rat liver of 24-methylene-24,25-dihydrolanosterol and 24,25-dihydrolanosterol. Biochem. Biophys. Res. Commun. 178 (1991) 1064–1071. [DOI] [PMID: 1872829]
5.  Aoyama, Y. and Yoshida, Y. The 4β-methyl group of substrate does not affect the activity of lanosterol 14α-demethylase (P45014DM) of yeast: differences between the substrate recognition by yeast and plant sterol 14α-demethylases. Biochem. Biophys. Res. Commun. 183 (1992) 1266–1272. [DOI] [PMID: 1567403]
6.  Bak, S., Kahn, R.A., Olsen, C.E. and Halkier, B.A. Cloning and expression in Escherichia coli of the obtusifoliol 14α-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P450 orthologous to the sterol 14α-demethylases (CYP51) from fungi and mammals. Plant J. 11 (1997) 191–201. [DOI] [PMID: 9076987]
[EC 1.14.14.154 created 2001 as EC 1.14.13.70, modified 2013, transferred 2018 EC 1.14.14.154]
 
 
EC 1.14.15.6     
Accepted name: cholesterol monooxygenase (side-chain-cleaving)
Reaction: cholesterol + 6 reduced adrenodoxin + 3 O2 + 6 H+ = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O (overall reaction)
(1a) cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
(1b) (22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
(1c) (20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
Other name(s): cholesterol desmolase; cytochrome P-450scc; C27-side chain cleavage enzyme; cholesterol 20-22-desmolase; cholesterol C20-22 desmolase; cholesterol side-chain cleavage enzyme; cholesterol side-chain-cleaving enzyme; steroid 20-22 desmolase; steroid 20-22-lyase; CYP11A1 (gene name)
Systematic name: cholesterol,reduced-adrenodoxin:oxygen oxidoreductase (side-chain-cleaving)
Comments: A heme-thiolate protein (cytochrome P-450). The reaction proceeds in three stages, with two hydroxylations at C-22 and C-20 preceding scission of the side-chain between carbons 20 and 22. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37292-81-2, 440354-98-3
References:
1.  Burstein, S., Middleditch, B.S. and Gut, M. Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation. J. Biol. Chem. 250 (1975) 9028–9037. [PMID: 1238395]
2.  Hanukoglu, I., Spitsberg, V., Bumpus, J.A., Dus, K.M. and Jefcoate, C.R. Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover. J. Biol. Chem. 256 (1981) 4321–4328. [PMID: 7217084]
3.  Hanukoglu, I. and Hanukoglu, Z. Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation. Eur. J. Biochem. 157 (1986) 27–31. [DOI] [PMID: 3011431]
4.  Strushkevich, N., MacKenzie, F., Cherkesova, T., Grabovec, I., Usanov, S. and Park, H.W. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc. Natl. Acad. Sci. USA 108 (2011) 10139–10143. [DOI] [PMID: 21636783]
5.  Mast, N., Annalora, A.J., Lodowski, D.T., Palczewski, K., Stout, C.D. and Pikuleva, I.A. Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J. Biol. Chem. 286 (2011) 5607–5613. [DOI] [PMID: 21159775]
[EC 1.14.15.6 created 1983, modified 2013, modified 2014]
 
 
EC 1.14.15.12      
Transferred entry: pimeloyl-[acyl-carrier protein] synthase. Now EC 1.14.14.46, pimeloyl-[acyl-carrier protein] synthase
[EC 1.14.15.12 created 2013, deleted 2017]
 
 
EC 1.14.15.15     
Accepted name: cholestanetriol 26-monooxygenase
Reaction: 5β-cholestane-3α,7α,12α-triol + 6 reduced adrenodoxin + 6 H+ + 3 O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 6 oxidized adrenodoxin + 4 H2O (overall reaction)
(1a) 5β-cholestane-3α,7α,12α-triol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 oxidized adrenodoxin + H2O
(1b) (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 oxidized adrenodoxin + 2 H2O
(1c) (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 2 oxidized adrenodoxin + H2O
For diagram of cholic acid biosynthesis (sidechain), click here
Other name(s): 5β-cholestane-3α,7α,12α-triol 26-hydroxylase; 5β-cholestane-3α,7α,12α-triol hydroxylase; cholestanetriol 26-hydroxylase; sterol 27-hydroxylase; sterol 26-hydroxylase; cholesterol 27-hydroxylase; CYP27A; CYP27A1; cytochrome P450 27A1′
Systematic name: 5β-cholestane-3α,7α,12α-triol,adrenodoxin:oxygen oxidoreductase (26-hydroxylating)
Comments: This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3β,7α-diol, 7α-hydroxycholest-4-en-3-one, and 5β-cholestane-3α,7α-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 52227-77-7
References:
1.  Masui, T., Herman, R. and Staple, E. The oxidation of 5β-cholestane-3α,7α,12α,26-tetraol to 5β-cholestane-3α,7α,12α-triol-26-oic acid via 5β-cholestane-3α,7α,12α-triol-26-al by rat liver. Biochim. Biophys. Acta 117 (1966) 266–268. [DOI] [PMID: 5914340]
2.  Okuda, K. and Hoshita, N. Oxidation of 5β-cholestane-3α,7α,12α-triol by rat-liver mitochondria. Biochim. Biophys. Acta 164 (1968) 381–388. [DOI] [PMID: 4388637]
3.  Wikvall, K. Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C27-steroids. J. Biol. Chem. 259 (1984) 3800–3804. [PMID: 6423637]
4.  Andersson, S., Davis, D.L., Dahlbäck, H., Jörnvall, H. and Russell, D.W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J. Biol. Chem. 264 (1989) 8222–8229. [PMID: 2722778]
5.  Dahlback, H. and Holmberg, I. Oxidation of 5β-cholestane-3α,7α,12α-triol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid by cytochrome P-45026 from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 167 (1990) 391–395. [DOI] [PMID: 2322231]
6.  Holmberg-Betsholtz, I., Lund, E., Björkhem, I. and Wikvall, K. Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5β-cholestane-3α,7α,12α,27-tetrol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid. J. Biol. Chem. 268 (1993) 11079–11085. [PMID: 8496170]
7.  Pikuleva, I.A., Babiker, A., Waterman, M.R. and Bjorkhem, I. Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways. J. Biol. Chem. 273 (1998) 18153–18160. [DOI] [PMID: 9660774]
8.  Furster, C., Bergman, T. and Wikvall, K. Biochemical characterization of a truncated form of CYP27A purified from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 263 (1999) 663–666. [DOI] [PMID: 10512735]
9.  Pikuleva, I.A., Puchkaev, A. and Björkhem, I. Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1. Biochemistry 40 (2001) 7621–7629. [DOI] [PMID: 11412116]
[EC 1.14.15.15 created 1976 as EC 1.14.13.15, modified 2005, modified 2012, transferred 2016 to EC 1.14.15.15]
 
 
EC 1.14.15.28     
Accepted name: cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]
Reaction: cholest-4-en-3-one + 6 reduced [2Fe-2S] ferredoxin + 3 O2 = (25R)-3-oxocholest-4-en-26-oate + 6 oxidized [2Fe-2S] ferredoxin + 4 H2O (overall reaction)
(1a) cholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-26-hydroxycholest-4-en-3-one + 2 oxidized [2Fe-2S] ferredoxin + H2O
(1b) (25R)-26-hydroxycholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-26-oxocholest-4-en-3-one + 2 oxidized [2Fe-2S] ferredoxin + 2 H2O
(1c) (25R)-26-oxocholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-3-oxocholest-4-en-26-oate + 2 oxidized [2Fe-2S] ferredoxin + H2O
Other name(s): CYP142
Systematic name: cholest-4-en-3-one,reduced [2Fe-2S] ferredoxin:oxygen oxidoreductase [(25R)-3-oxocholest-4-en-26-oate forming]
Comments: This cytochrome P-450 (heme-thiolate) enzyme, found in several bacterial pathogens, is involved in degradation of the host cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol. The products are exclusively in the (25R) conformation. The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.29, cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]. The enzyme can receive electrons from ferredoxin reductase in vitro, its natural electron donor is not known yet.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Driscoll, M.D., McLean, K.J., Levy, C., Mast, N., Pikuleva, I.A., Lafite, P., Rigby, S.E., Leys, D. and Munro, A.W. Structural and biochemical characterization of Mycobacterium tuberculosis CYP142: evidence for multiple cholesterol 27-hydroxylase activities in a human pathogen. J. Biol. Chem. 285 (2010) 38270–38282. [DOI] [PMID: 20889498]
2.  Johnston, J.B., Ouellet, H. and Ortiz de Montellano, P.R. Functional redundancy of steroid C26-monooxygenase activity in Mycobacterium tuberculosis revealed by biochemical and genetic analyses. J. Biol. Chem. 285 (2010) 36352–36360. [DOI] [PMID: 20843794]
[EC 1.14.15.28 created 2016 as EC 1.14.13.221, transferred 2018 to EC 1.14.15.28]
 
 
EC 1.14.15.29     
Accepted name: cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]
Reaction: cholest-4-en-3-one + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2 = (25S)-3-oxocholest-4-en-26-oate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O (overall reaction)
(1a) cholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-hydroxycholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) (25S)-26-hydroxycholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-oxocholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(1c) (25S)-26-oxocholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-3-oxocholest-4-en-26-oate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
Other name(s): CYP125; CYP125A1; cholest-4-en-3-one 27-monooxygenase (misleading); cholest-4-en-3-one,NADH:oxygen oxidoreductase (26-hydroxylating); cholest-4-en-3-one 26-monooxygenase (ambiguous)
Systematic name: cholest-4-en-3-one,[reduced ferredoxin]:oxygen oxidoreductase [(25S)-3-oxocholest-4-en-26-oate forming]
Comments: A cytochrome P-450 (heme-thiolate) protein found in several bacterial pathogens. The enzyme is involved in degradation of the host’s cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol [4]. The products are exclusively in the (25S) configuration. The enzyme is part of a two-component system that also includes a ferredoxin reductase (most likely KshB, which also interacts with EC 1.14.15.30, 3-ketosteroid 9α-monooxygenase). The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.28, cholest-4-en-3-one 27-monooxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Rosloniec, K.Z., Wilbrink, M.H., Capyk, J.K., Mohn, W.W., Ostendorf, M., van der Geize, R., Dijkhuizen, L. and Eltis, L.D. Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1. Mol. Microbiol. 74 (2009) 1031–1043. [DOI] [PMID: 19843222]
2.  McLean, K.J., Lafite, P., Levy, C., Cheesman, M.R., Mast, N., Pikuleva, I.A., Leys, D. and Munro, A.W. The Structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection. J. Biol. Chem. 284 (2009) 35524–35533. [DOI] [PMID: 19846552]
3.  Capyk, J.K., Kalscheuer, R., Stewart, G.R., Liu, J., Kwon, H., Zhao, R., Okamoto, S., Jacobs, W.R., Jr., Eltis, L.D. and Mohn, W.W. Mycobacterial cytochrome P450 125 (Cyp125) catalyzes the terminal hydroxylation of C27 steroids. J. Biol. Chem. 284 (2009) 35534–35542. [DOI] [PMID: 19846551]
4.  Ouellet, H., Guan, S., Johnston, J.B., Chow, E.D., Kells, P.M., Burlingame, A.L., Cox, J.S., Podust, L.M. and de Montellano, P.R. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol. Microbiol. 77 (2010) 730–742. [DOI] [PMID: 20545858]
[EC 1.14.15.29 created 2012 as EC 1.14.13.141, modified 2016, transferred 2018 to EC 1.14.15.29]
 
 
EC 1.14.15.30     
Accepted name: 3-ketosteroid 9α-monooxygenase
Reaction: androsta-1,4-diene-3,17-dione + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = 9α-hydroxyandrosta-1,4-diene-3,17-dione + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
Other name(s): KshA; 3-ketosteroid 9α-hydroxylase
Systematic name: androsta-1,4-diene-3,17-dione,[reduced ferredoxin]:oxygen oxidoreductase (9α-hydroxylating)
Comments: The enzyme is involved in the cholesterol degradation pathway of several bacterial pathogens, such as Mycobacterium tuberculosis. It forms a two-component system with a ferredoxin reductase (KshB). The enzyme contains a Rieske-type iron-sulfur center and non-heme iron. The product of the enzyme is unstable, and spontaneously converts to 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, UM-BBD
References:
1.  Petrusma, M., Dijkhuizen, L. and van der Geize, R. Rhodococcus rhodochrous DSM 43269 3-ketosteroid 9α-hydroxylase, a two-component iron-sulfur-containing monooxygenase with subtle steroid substrate specificity. Appl. Environ. Microbiol. 75 (2009) 5300–5307. [DOI] [PMID: 19561185]
2.  Capyk, J.K., D'Angelo, I., Strynadka, N.C. and Eltis, L.D. Characterization of 3-ketosteroid 9α-hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of Mycobacterium tuberculosis. J. Biol. Chem. 284 (2009) 9937–9946. [DOI] [PMID: 19234303]
3.  Capyk, J.K., Casabon, I., Gruninger, R., Strynadka, N.C. and Eltis, L.D. Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis. J. Biol. Chem. 286 (2011) 40717–40724. [DOI] [PMID: 21987574]
[EC 1.14.15.30 created 2012 as EC 1.14.13.142, transferred 2018 to EC 1.14.15.30]
 
 
EC 1.14.18.8     
Accepted name: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase
Reaction: 7α-hydroxycholest-4-en-3-one + 2 ferrocytochrome b5 + 2 H+ + O2 = 7α,12α-dihydroxycholest-4-en-3-one + 2 ferricytochrome b5 + + H2O
For diagram of cholesterol catabolism (rings A, B and C), click here
Other name(s): 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; CYP12; sterol 12α-hydroxylase (ambiguous); HCO 12α-hydroxylase
Systematic name: 7α-hydroxycholest-4-en-3-one,ferrocytochrome-b5:oxygen oxidoreductase (12α-hydroxylating)
Comments: A P-450 heme-thiolate protein. Requires EC 1.6.2.4, NADPH—hemoprotein reductase and cytochrome b5 for maximal activity. This enzyme is important in bile acid biosynthesis, being responsible for the balance between the formation of cholic acid and chenodeoxycholic acid [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  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]
2.  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]
3.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8]
 
 
EC 1.14.18.9     
Accepted name: 4α-methylsterol monooxygenase
Reaction: 4,4-dimethyl-5α-cholest-7-en-3β-ol + 6 ferrocytochrome b5 + 3 O2 + 6 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 6 ferricytochrome b5 + 4 H2O (overall reaction)
(1a) 4,4-dimethyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 4α-hydroxymethyl-4β-methyl-5α-cholest-7-en-3β-ol + 2 ferricytochrome b5 + H2O
(1b) 4α-hydroxymethyl-4β-methyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferricytochrome b5 + 2 H2O
(1c) 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 2 ferricytochrome b5 + H2O
For diagram of sterol ring A modification, click here
Other name(s): methylsterol hydroxylase (ambiguous); 4-methylsterol oxidase (ambiguous); 4,4-dimethyl-5α-cholest-7-en-3β-ol,hydrogen-donor:oxygen oxidoreductase (hydroxylating) (ambiguous); methylsterol monooxygenase (ambiguous); ERG25 (gene name); MSMO1 (gene name); 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b5:oxygen oxidoreductase (hydroxylating) (ambiguous)
Systematic name: 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b5:oxygen oxidoreductase (C4α-methyl-hydroxylating)
Comments: This enzyme is found in fungi and animals and catalyses a step in the biosynthesis of important sterol molecules such as ergosterol and cholesterol, respectively. The enzyme acts on the 4α-methyl group. Subsequent decarboxylation by EC 1.1.1.170, 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating), occurs concomitantly with epimerization of the remaining 4β-methyl into the 4α position, thus making it a suitable substrate for a second round of catalysis. cf. EC 1.14.13.246, 4β-methylsterol monooxygenase; EC 1.14.18.10, plant 4,4-dimethylsterol C-4α-methyl-monooxygenase; and EC 1.14.18.11, plant 4α-monomethylsterol monooxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37256-80-7
References:
1.  Miller, W.L., Kalafer, M.E., Gaylor, J.L. and Delwicke, C.V. Investigation of the component reactions of oxidative sterol demethylation. Study of the aerobic and anaerobic processes. Biochemistry 6 (1967) 2673–2678. [PMID: 4383278]
2.  Gaylor, J.L. and Mason, H.S. Investigation of the component reactions of oxidative sterol demethylation. Evidence against participation of cytochrome P-450. J. Biol. Chem. 243 (1968) 4966–4972. [PMID: 4234469]
3.  Sharpless, K.B., Snyder, T.E., Spencer, T.A., Maheshwari, K.K. and Nelson, J.A. Biological demethylation of 4,4-dimethyl sterols, Evidence for enzymic epimerization of the 4β-methyl group prior to its oxidative removal. J. Am. Chem. Soc. 91 (1969) 3394–3396. [PMID: 5791927]
4.  Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624–10629. [PMID: 7430141]
5.  Fukushima, H., Grinstead, G.F. and Gaylor, J.L. Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b5-dependence of 4-methyl sterol oxidase. J. Biol. Chem. 256 (1981) 4822–4826. [PMID: 7228857]
6.  Kawata, S., Trzaskos, J.M. and Gaylor, J.L. Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. J. Biol. Chem. 261 (1986) 3790–3799. [PMID: 3949790]
[EC 1.14.18.9 created 1972 as EC 1.14.99.16, transferred 2002 to EC 1.14.13.72, transferred 2017 to EC 1.14.18.9, modified 2019]
 
 
EC 1.14.19.20     
Accepted name: Δ7-sterol 5(6)-desaturase
Reaction: a Δ7-sterol + 2 ferrocytochrome b5 + O2 + 2 H+ = a Δ5,7-sterol + 2 ferricytochrome b5 + 2 H2O
For diagram of the modification of sterol rings B, C and D, click here
Other name(s): lathosterol oxidase; Δ7-sterol Δ5-dehydrogenase; Δ7-sterol 5-desaturase; Δ7-sterol-C5(6)-desaturase; 5-DES; SC5DL (gene name); ERG3 (gene name)
Systematic name: Δ7-sterol,ferrocytochrome b5:oxygen oxidoreductase 5,6-dehydrogenating
Comments: This enzyme, found in eukaryotic organisms, catalyses the introduction of a double bond between the C5 and C6 carbons of the B ring of Δ7-sterols, to yield the corresponding Δ5,7-sterols. The enzymes from yeast, plants and vertebrates act on avenasterol, episterol, and lathosterol, respectively. The enzyme is located at the endoplasmic reticulum and is membrane bound.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37255-37-1
References:
1.  Dempsey, M.E., Seaton, J.D., Schroepfer, G.J. and Trockman, R.W. The intermediary role of Δ5,7-cholestadien-3β-ol in cholesterol biosynthesis. J. Biol. Chem. 239 (1964) 1381–1387. [PMID: 14189869]
2.  Honjo, K., Ishibashi, T. and Imai, Y. Partial purification and characterization of lathosterol 5-desaturase from rat liver microsomes. J. Biochem. 97 (1985) 955–959. [PMID: 4019441]
3.  Arthington, B.A., Bennett, L.G., Skatrud, P.L., Guynn, C.J., Barbuch, R.J., Ulbright, C.E. and Bard, M. Cloning, disruption and sequence of the gene encoding yeast C-5 sterol desaturase. Gene 102 (1991) 39–44. [DOI] [PMID: 1864507]
4.  Taton, M. and Rahier, A. Plant sterol biosynthesis: identification and characterization of higher plant Δ7-sterol C5(6)-desaturase. Arch. Biochem. Biophys. 325 (1996) 279–288. [DOI] [PMID: 8561508]
5.  Nishino, H., Nakaya, J., Nishi, S., Kurosawa, T. and Ishibashi, T. Temperature-induced differential kinetic properties between an initial burst and the following steady state in membrane-bound enzymes: studies on lathosterol 5-desaturase. Arch. Biochem. Biophys. 339 (1997) 298–304. [DOI] [PMID: 9056262]
6.  Taton, M., Husselstein, T., Benveniste, P. and Rahier, A. Role of highly conserved residues in the reaction catalyzed by recombinant Δ7-sterol-C5(6)-desaturase studied by site-directed mutagenesis. Biochemistry 39 (2000) 701–711. [DOI] [PMID: 10651635]
7.  Poklepovich, T.J., Rinaldi, M.A., Tomazic, M.L., Favale, N.O., Turkewitz, A.P., Nudel, C.B. and Nusblat, A.D. The cytochrome b5 dependent C-5(6) sterol desaturase DES5A from the endoplasmic reticulum of Tetrahymena thermophila complements ergosterol biosynthesis mutants in Saccharomyces cerevisiae. Steroids 77 (2012) 1313–1320. [DOI] [PMID: 22982564]
[EC 1.14.19.20 created 1972 as EC 1.3.3.2, transferred 2005 to EC 1.14.21.6, transferred 2015 to EC 1.14.19.20]
 
 
EC 1.14.19.21     
Accepted name: cholesterol 7-desaturase
Reaction: cholesterol + O2 + NAD(P)H + H+ = cholesta-5,7-dien-3β-ol + NAD(P)+ + 2 H2O
Other name(s): nvd (gene name); daf-36 (gene name)
Systematic name: cholesterol,NAD(P)H:oxygen oxidoreductase (7,8 dehydrogenating)
Comments: The enzyme, characterized from several organisms including the worm Caenorhabditis elegans, the fly Drosophila melanogaster, and the ciliate Tetrahymena thermophila, is a Rieske oxygenase. In insects it participates in the the biosythesis of ecdysteroid hormones. The electrons are transferred from NAD(P)H via an electron transfer chain likely to include ferredoxin reductase and ferredoxin. The enzyme differs from regular desaturases, such as EC 1.14.19.20, 7-sterol 5(6)-desaturase, which are cytochrome b5-dependent and contain the three His-boxes that are typical to most desaturases.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Yoshiyama-Yanagawa, T., Enya, S., Shimada-Niwa, Y., Yaguchi, S., Haramoto, Y., Matsuya, T., Shiomi, K., Sasakura, Y., Takahashi, S., Asashima, M., Kataoka, H. and Niwa, R. The conserved Rieske oxygenase DAF-36/Neverland is a novel cholesterol-metabolizing enzyme. J. Biol. Chem. 286 (2011) 25756–25762. [DOI] [PMID: 21632547]
2.  Wollam, J., Magomedova, L., Magner, D.B., Shen, Y., Rottiers, V., Motola, D.L., Mangelsdorf, D.J., Cummins, C.L. and Antebi, A. The Rieske oxygenase DAF-36 functions as a cholesterol 7-desaturase in steroidogenic pathways governing longevity. Aging Cell 10 (2011) 879–884. [DOI] [PMID: 21749634]
3.  Najle, S.R., Nusblat, A.D., Nudel, C.B. and Uttaro, A.D. The sterol-C7 desaturase from the ciliate Tetrahymena thermophila is a Rieske oxygenase, which is highly conserved in animals. Mol. Biol. Evol. 30 (2013) 1630–1643. [DOI] [PMID: 23603937]
4.  Barry, S.M. and Challis, G.L. Mechanism and catalytic diversity of Rieske non-heme iron-dependent oxygenases. ACS Catal. 3 (2013) 2362–2370. [DOI] [PMID: 24244885]
[EC 1.14.19.21 created 2015]
 
 
EC 1.14.21.6      
Transferred entry: lathosterol oxidase. Now EC 1.14.19.20, Δ7-sterol 5(6)-desaturase
[EC 1.14.21.6 created 1972 as EC 1.3.3.2, transferred 2005 to EC 1.14.21.6, deleted 2015]
 
 
EC 1.14.99.7      
Transferred entry: squalene monooxygenase. Transferred to EC 1.14.13.132, squalene monooxygenase.
[EC 1.14.99.7 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7 rest to EC 5.4.99.7, deleted 2011]
 
 
EC 1.14.99.38     
Accepted name: cholesterol 25-hydroxylase
Reaction: cholesterol + reduced acceptor + O2 = 25-hydroxycholesterol + acceptor + H2O
For diagram of cholic acid biosynthesis (sidechain), click here
Glossary: cholesterol = cholest-5-en-3β-ol
Other name(s): cholesterol 25-monooxygenase
Systematic name: cholesterol,hydrogen-donor:oxygen oxidoreductase (25-hydroxylating)
Comments: Unlike most other sterol hydroxylases, this enzyme is not a cytochrome P-450. Instead, it uses diiron cofactors to catalyse the hydroxylation of hydrophobic substrates [1]. The diiron cofactor can be either Fe-O-Fe or Fe-OH-Fe and is bound to the enzyme through interactions with clustered histidine or glutamate residues [4,5]. In cell cultures, this enzyme down-regulates cholesterol synthesis and the processing of sterol regulatory element binding proteins (SREBPs).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 60202-07-5
References:
1.  Lund, E.G., Kerr, T.A., Sakai, J., Li, W.P. and Russell, D.W. cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. J. Biol. Chem. 273 (1998) 34316–34327. [DOI] [PMID: 9852097]
2.  Chen, J.J., Lukyanenko, Y. and Hutson, J.C. 25-Hydroxycholesterol is produced by testicular macrophages during the early postnatal period and influences differentiation of Leydig cells in vitro. Biol. Reprod. 66 (2002) 1336–1341. [PMID: 11967195]
3.  Lukyanenko, Y., Chen, J.J. and Hutson, J.C. Testosterone regulates 25-hydroxycholesterol production in testicular macrophages. Biol. Reprod. 67 (2002) 1435–1438. [PMID: 12390873]
4.  Fox, B.G., Shanklin, J., Ai, J., Loehr, T.M. and Sanders-Loehr, J. Resonance Raman evidence for an Fe-O-Fe center in stearoyl-ACP desaturase. Primary sequence identity with other diiron-oxo proteins. Biochemistry 33 (1994) 12776–12786. [PMID: 7947683]
5.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.99.38 created 2005]
 
 
EC 2.3.1.26     
Accepted name: sterol O-acyltransferase
Reaction: a long-chain acyl-CoA + a sterol = CoA + a long-chain 3-hydroxysterol ester
Other name(s): cholesterol acyltransferase; sterol-ester synthase; acyl coenzyme A-cholesterol-O-acyltransferase; acyl-CoA:cholesterol acyltransferase; ACAT; acylcoenzyme A:cholesterol O-acyltransferase; cholesterol ester synthase; cholesterol ester synthetase; cholesteryl ester synthetase; SOAT1 (gene name); SOAT2 (gene name); ARE1 (gene name); ARE2 (gene name); acyl-CoA:cholesterol O-acyltransferase
Systematic name: long-chain acyl-CoA:sterol O-acyltransferase
Comments: The enzyme catalyses the formation of sterol esters from a sterol and long-chain fatty acyl-coenzyme A. The enzyme from yeast, but not from mammals, prefers monounsaturated acyl-CoA. In mammals the enzyme acts mainly on cholesterol and forms cholesterol esters that are stored in cytosolic droplets, which may serve to protect cells from the toxicity of free cholesterol. In macrophages, the accumulation of cytosolic droplets of cholesterol esters results in the formation of `foam cells’, a hallmark of early atherosclerotic lesions. In hepatocytes and enterocytes, cholesterol esters can be incorporated into apolipoprotein B-containing lipoproteins for secretion from the cell.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9027-63-8
References:
1.  Spector, A.A., Mathur, S.N. and Kaduce, T.L. Role of acylcoenzyme A: cholesterol O-acyltransferase in cholesterol metabolism. Prog. Lipid Res. 18 (1979) 31–53. [DOI] [PMID: 42927]
2.  Taketani, S., Nishino, T. and Katsuki, H. Characterization of sterol-ester synthetase in Saccharomyces cerevisiae. Biochim. Biophys. Acta 575 (1979) 148–155. [DOI] [PMID: 389289]
3.  Lee, O., Chang, C.C., Lee, W. and Chang, T.Y. Immunodepletion experiments suggest that acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) protein plays a major catalytic role in adult human liver, adrenal gland, macrophages, and kidney, but not in intestines. J. Lipid Res. 39 (1998) 1722–1727. [PMID: 9717734]
4.  Yang, H., Cromley, D., Wang, H., Billheimer, J.T. and Sturley, S.L. Functional expression of a cDNA to human acyl-coenzyme A:cholesterol acyltransferase in yeast. Species-dependent substrate specificity and inhibitor sensitivity. J. Biol. Chem. 272 (1997) 3980–3985. [PMID: 9020103]
5.  Chang, C.C., Lee, C.Y., Chang, E.T., Cruz, J.C., Levesque, M.C. and Chang, T.Y. Recombinant acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) purified to essential homogeneity utilizes cholesterol in mixed micelles or in vesicles in a highly cooperative manner. J. Biol. Chem. 273 (1998) 35132–35141. [PMID: 9857049]
6.  Das, A., Davis, M.A. and Rudel, L.L. Identification of putative active site residues of ACAT enzymes. J. Lipid Res. 49 (2008) 1770–1781. [PMID: 18480028]
[EC 2.3.1.26 created 1972, modified 2019]
 
 


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