The Enzyme Database

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EC 1.1.1.51     
Accepted name: 3(or 17)β-hydroxysteroid dehydrogenase
Reaction: testosterone + NAD(P)+ = androstenedione + NAD(P)H + H+
Glossary: androstenedione = androst-4-ene-3,17-dione
Other name(s): β-hydroxy steroid dehydrogenase; 17-ketoreductase; 17β-hydroxy steroid dehydrogenase; 3β-hydroxysteroid dehydrogenase; 3β-hydroxy steroid dehydrogenase
Systematic name: 3(or 17)β-hydroxysteroid:NAD(P)+ oxidoreductase
Comments: Also acts on other 3β- or 17β-hydroxysteroids. cf. EC 1.1.1.209 3(or 17)α-hydroxysteroid dehydrogenase.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, UM-BBD, CAS registry number: 9015-81-0
References:
1.  Dahm, K. and Breuer, H. Anreicherung einer 17β-hydroxysteroid:NAD(P)-oxydoreduktase aus der Nebenniere der Ratte. Hoppe-Seyler's Z. Physiol. Chem. 336 (1964) 63–68. [PMID: 14214322]
2.  Lynn, W.S. and Brown, R.H. The conversion of progesterone to androgens by testes. J. Biol. Chem. 232 (1958) 1015–1030. [PMID: 13549484]
3.  Marcus, P.I. and Talalay, P. Induction and purification of α- and β-hydroxysteroid dehydrogenases. J. Biol. Chem. 218 (1956) 661–674. [PMID: 13295221]
4.  Schultz, R.M., Groman, F.V. and Engel, L.L. 3(17)β-Hydroxysteroid dehydrogenase of Pseudomonas testosteroni. A convenient purification and demonstration of multiple molecular forms. J. Biol. Chem. 252 (1977) 3775–3783. [PMID: 193845]
5.  Talalay, P. and Dobson, M.M. Purification and properties of a α-hydroxysteroid dehydrogenase. J. Biol. Chem. 205 (1953) 823–837. [PMID: 13129261]
[EC 1.1.1.51 created 1961]
 
 
EC 1.1.1.53     
Accepted name: 3α(or 20β)-hydroxysteroid dehydrogenase
Reaction: androstan-3α,17β-diol + NAD+ = 17β-hydroxyandrostan-3-one + NADH + H+
Other name(s): cortisone reductase; (R)-20-hydroxysteroid dehydrogenase; 20β-hydroxy steroid dehydrogenase; Δ4-3-ketosteroid hydrogenase; 20β-hydroxysteroid dehydrogenase; 3α,20β-hydroxysteroid:NAD+-oxidoreductase; NADH-20β-hydroxysteroid dehydrogenase; 20β-HSD
Systematic name: 3α(or 20β)-hydroxysteroid:NAD+ oxidoreductase
Comments: The 3α-hydroxy group or 20β-hydroxy group of pregnane and androstane steroids can act as donor.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-42-6
References:
1.  Edwards, C.A.F. and Orr, J.C. Comparison of the 3α-and 20β-hydroxysteroid dehydrogenase activities of the cortisone reductase of Streptomyces hydrogenans. Biochemistry 17 (1978) 4370–4376. [PMID: 718844]
2.  Hübener, H.J. and Sahrholz, F.G. 20β-hydroxy-steroid-dehydrogenase. II. Darstellung und Kristallisation. Biochem. Z. 333 (1960) 95–105. [PMID: 14403761]
3.  Hübener, H.J., Sahrholz, F.G., Schmidt-Thomé, J., Nesemann, G. and Junk, R. 20β-Hydroxy-Steroid-Dehydrogenase, ein neues kristallines Enzym. Biochim. Biophys. Acta 35 (1959) 270–272. [PMID: 14403760]
4.  Lynn, W.S. and Brown, R.H. The conversion of progesterone to androgens by testes. J. Biol. Chem. 232 (1958) 1015–1030. [PMID: 13549484]
5.  Strickler, R.C., Covey, D.F. and Tobias, B. Study of 3α, 20 β-hydroxysteroid dehydrogenase with an enzyme-generated affinity alkylator: dual enzyme activity at a single active site. Biochemistry 19 (1980) 4950–4954. [PMID: 6936053]
6.  Sweet, F. and Samant, B.S. Bifunctional enzyme activity at the same active site: study of 3α and 20β activity by affinity alkylation of 3α, 20β-hydroxysteroid dehydrogenase with 17-(bromoacetoxy)steroids. Biochemistry 19 (1980) 978–986. [PMID: 6928375]
[EC 1.1.1.53 created 1961, modified 1986]
 
 
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 1.1.1.149     
Accepted name: 20α-hydroxysteroid dehydrogenase
Reaction: 17α,20α-dihydroxypregn-4-en-3-one + NAD(P)+ = 17α-hydroxyprogesterone + NAD(P)H + H+
Other name(s): 20α-hydroxy steroid dehydrogenase; 20α-HSD; 20α-HSDH
Systematic name: 20α-hydroxysteroid:NAD(P)+ 20-oxidoreductase
Comments: Re-specific with respect to NAD(P)+ (cf. EC 1.1.1.62 17β-estradiol 17-dehydrogenase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9040-08-8
References:
1.  Shikita, M., Inano, H. and Tamaoki, B. Further studies on 20α-hydroxysteroid dehydrogenase of rat testes. Biochemistry 6 (1967) 1760–1764. [PMID: 4382486]
2.  Strickler, R.C., Tobias, B. and Covey, D.F. Human placental 17β-estradiol dehydrogenase and 20α-hydroxysteroid dehydrogenase. Two activities at a single enzyme active site. J. Biol. Chem. 256 (1981) 316–321. [PMID: 6935192]
[EC 1.1.1.149 created 1972, deleted 1983, reinstated 1986]
 
 
EC 1.1.1.210     
Accepted name: 3β(or 20α)-hydroxysteroid dehydrogenase
Reaction: 5α-androstan-3β,17β-diol + NADP+ = 17β-hydroxy-5α-androstan-3-one + NADPH + H+
Other name(s): progesterone reductase; dehydrogenase, 3β,20α-hydroxy steroid; 3β,20α-hydroxysteroid oxidoreductase
Systematic name: 3β(or 20α)-hydroxysteroid:NADP+ oxidoreductase
Comments: Also acts on 20α-hydroxysteroids.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 82869-26-9
References:
1.  Sharaf, M.A. and Sweet, F. Dual activity at an enzyme active site: 3β,20α-hydroxysteroid oxidoreductase from fetal blood. Biochemistry 21 (1982) 4615–4620. [PMID: 6958329]
[EC 1.1.1.210 created 1986]
 
 
EC 1.1.1.277     
Accepted name: 3β-hydroxy-5β-steroid dehydrogenase
Reaction: 3β-hydroxy-5β-pregnane-20-one + NADP+ = 5β-pregnan-3,20-dione + NADPH + H+
For diagram of reaction, click here
Other name(s): 3β-hydroxysteroid 5β-oxidoreductase; 3β-hydroxysteroid 5β-progesterone oxidoreductase
Systematic name: 3β-hydroxy-5β-steroid:NADP+ 3-oxidoreductase
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 162731-81-9
References:
1.  Stuhlemmer, U. and Kreis, W. Cardenolide formation and activity of pregnane-modifying enzymes in cell suspension cultures, shoot cultures and leaves of Digitalis lanata. Plant Physiol. 34 (1996) 85–91.
2.  Seitz, H.U. and Gaertner, D.E. Enzymes in cardenolide-accumulating shoot cultures of Digitalis purpurea. Plant Cell 38 (1994) 337–344.
3.  Lindemann, P. and Luckner, M. Biosynthesis of pregnane derivatives in somatic embryos of Digitalis lanata. Phytochemistry 46 (1997) 507–513.
[EC 1.1.1.277 created 2003]
 
 
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 1.3.1.22     
Accepted name: 3-oxo-5α-steroid 4-dehydrogenase (NADP+)
Reaction: a 3-oxo-5α-steroid + NADP+ = a 3-oxo-Δ4-steroid + NADPH + H+
Other name(s): cholestenone 5α-reductase; testosterone Δ4-5α-reductase; steroid 5α-reductase; 3-oxosteroid Δ4-dehydrogenase; 5α-reductase; steroid 5α-hydrogenase; 3-oxosteroid 5α-reductase; testosterone Δ4-hydrogenase; 4-ene-3-oxosteroid 5α-reductase; reduced nicotinamide adenine dinucleotide phosphate:Δ4-3-ketosteroid 5α-oxidoreductase; 4-ene-5α-reductase; Δ4-3-ketosteroid 5α-oxidoreductase; cholest-4-en-3-one 5α-reductase; testosterone 5α-reductase; 3-oxo-5α-steroid 4-dehydrogenase
Systematic name: 3-oxo-5α-steroid:NADP+ Δ4-oxidoreductase
Comments: The enzyme catalyses the conversion of assorted 3-oxo-Δ4 steroids into their corresponding 5α form. Substrates for the mammalian enzyme include testosterone, progesterone, and corticosterone. Substrates for the plant enzyme are brassinosteroids such as campest-4-en-3-one and (22α)-hydroxy-campest-4-en-3-one. cf. EC 1.3.99.5, 3-oxo-5α-steroid 4-dehydrogenase (acceptor).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37255-34-8
References:
1.  Levy, H.R. and Talalay, P. Bacterial oxidation of steroids. II. Studies on the enzymatic mechanisms of ring A dehydrogenation. J. Biol. Chem. 234 (1959) 2014–2021. [PMID: 13673006]
2.  Shefer, S., Hauser, S. and Mosbach, E.H. Studies on the biosynthesis of 5α-cholestan-3β-ol. I. Cholestenone 5α-reductase of rat liver. J. Biol. Chem. 241 (1966) 946–952. [PMID: 5907469]
3.  Cheng, Y.-J. and Karavolas, H.J. Properties and subcellular distribution of Δ4-steroid (progesterone) 5α-reductase in rat anterior pituitary. Steroids 26 (1975) 57–71. [DOI] [PMID: 1166484]
4.  Sargent, N.S. and Habib, F.K. Partial purification of human prostatic 5α-reductase (3-oxo-5α-steroid:NADP+ 4-ene-oxido-reductase; EC 1.3.1.22) in a stable and active form. J. Steroid Biochem. Mol. Biol. 38 (1991) 73–77. [DOI] [PMID: 1705142]
5.  Quemener, E., Amet, Y., di Stefano, S., Fournier, G., Floch, H.H. and Abalain, J.H. Purification of testosterone 5α-reductase from human prostate by a four-step chromatographic procedure. Steroids 59 (1994) 712–718. [DOI] [PMID: 7900170]
6.  Poletti, A., Celotti, F., Rumio, C., Rabuffetti, M. and Martini, L. Identification of type 1 5α-reductase in myelin membranes of male and female rat brain. Mol. Cell. Endocrinol. 129 (1997) 181–190. [DOI] [PMID: 9202401]
7.  Li, J., Biswas, M.G., Chao, A., Russell, D.W. and Chory, J. Conservation of function between mammalian and plant steroid 5α-reductases. Proc. Natl. Acad. Sci. USA 94 (1997) 3554–3559. [DOI] [PMID: 9108014]
8.  Rosati, F., Bardazzi, I., De Blasi, P., Simi, L., Scarpi, D., Guarna, A., Serio, M., Racchi, M.L. and Danza, G. 5α-Reductase activity in Lycopersicon esculentum: cloning and functional characterization of LeDET2 and evidence of the presence of two isoenzymes. J. Steroid Biochem. Mol. Biol. 96 (2005) 287–299. [DOI] [PMID: 15993049]
[EC 1.3.1.22 created 1972, modified 2012]
 
 
EC 1.3.1.30      
Transferred entry: EC 1.3.1.30, progesterone 5α-reductase, transferred to EC 1.3.1.22, 3-oxo-5α-steroid 4-dehydrogenase (NADP+).
[EC 1.3.1.30 created 1978, deleted 2012]
 
 
EC 1.14.13.54     
Accepted name: ketosteroid monooxygenase
Reaction: a ketosteroid + NADPH + H+ + O2 = a steroid ester/lactone + NADP+ + H2O (general reaction)
(1) progesterone + NADPH + H+ + O2 = testosterone acetate + NADP+ + H2O
(2) androstenedione + NADPH + H+ + O2 = testololactone + NADP+ + H2O
(3) 17α-hydroxyprogesterone + NADPH + H+ + O2 = androstenedione + acetate + NADP+ + H2O
Glossary: progesterone = pregn-4-ene-3,20-dione
testosterone acetate = 3-oxoandrost-4-en-17β-yl acetate
androstenedione = androst-4-ene-3,17-dione
testololactone = 3-oxo-13,17-secoandrost-4-eno-17,13α-lactone
17α-hydroxyprogesterone = 17α-hydroxypregn-4-ene-3,20-dione
Other name(s): steroid-ketone monooxygenase; progesterone, NADPH2:oxygen oxidoreductase (20-hydroxylating, ester-producing); 17α-hydroxyprogesterone, NADPH2:oxygen oxidoreductase (20-hydroxylating, side-chain cleaving); androstenedione, NADPH2:oxygen oxidoreductase (17-hydroxylating, lactonizing)
Systematic name: ketosteroid,NADPH:oxygen oxidoreductase (20-hydroxylating, ester-producing/20-hydroxylating, side-chain cleaving/17-hydroxylating, lactonizing)
Comments: A single FAD-containing enzyme catalyses three types of monooxygenase (Baeyer-Villiger oxidation) reaction. The oxidative esterification of a number of derivatives of progesterone to produce the corresponding 17α-hydroxysteroid 17-acetate ester, such as testosterone acetate, is shown in Reaction (1). The oxidative lactonization of a number of derivatives of androstenedione to produce the 13,17-secoandrosteno-17,13α-lactone, such as testololactone, is shown in Reaction (2). The oxidative cleavage of the 17β-side-chain of 17α-hydroxyprogesterone to produce androstenedione and acetate is shown in Reaction (3). Reaction (1) is also catalysed by EC 1.14.99.4 (progesterone monooxygenase), and Reactions (2) and (3) correspond to that catalysed by EC 1.14.99.12 (androst-4-ene-3,17-dione monooxygenase). The possibility that a single enzyme is responsible for the reactions ascribed to EC 1.14.99.4 and EC 1.14.99.12 in other tissues cannot be excluded.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9044-53-5
References:
1.  Katagiri, M. and Itagaki, E. A steroid ketone monooxygenase from Cylindrocarpon radicicola. In: Müller, F. (Ed.), Chemistry and Biochemistry of Flavoenzymes, CRC Press, Florida, 1991, pp. 102–108.
2.  Itagaki, E. Studies on a steroid monooxygenase from Cylindrocarpon radicicola ATCC 11011. Purification and characterization. J. Biochem. (Tokyo) 99 (1986) 815–824. [PMID: 3486863]
3.  Itagaki, E. Studies on a steroid monooxygenase from Cylindrocarpon radicicola ATCC11011. Oxygenative lactonization of androstenedione to testololactone. J. Biochem. (Tokyo) 99 (1986) 825–832. [PMID: 3486864]
[EC 1.14.13.54 created 1999]
 
 
EC 1.14.14.16     
Accepted name: steroid 21-monooxygenase
Reaction: a C21 steroid + [reduced NADPH—hemoprotein reductase] + O2 = a 21-hydroxy-C21-steroid + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): steroid 21-hydroxylase; 21-hydroxylase; P450c21; CYP21A2 (gene name)
Systematic name: steroid,NADPH—hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
Comments: A P-450 heme-thiolate protein responsible for the conversion of progesterone and 17α-hydroxyprogesterone to their respective 21-hydroxylated derivatives, 11-deoxycorticosterone and 11-deoxycortisol. Involved in the biosynthesis of the hormones aldosterone and cortisol. The electron donor is EC 1.6.2.4, NADPH—hemoprotein reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-68-9
References:
1.  Hayano, M. and Dorfman, R.I. The action of adrenal homogenates on progesterone, 17-hydroxyprogesterone and 21-desoxycortisone. Arch. Biochem. Biophys. 36 (1952) 237–239. [DOI] [PMID: 14934270]
2.  Plager, J.E. and Samuels, L.T. Synthesis of C14-17-hydroxy-11-desoxycorticosterone and 17-hydroxycorticosterone by fractionated extracts of adrenal homogenates. Arch. Biochem. Biophys. 42 (1953) 477–478. [DOI] [PMID: 13031650]
3.  Ryan, K.J. and Engel, L.L. Hydroxylation of steroids at carbon 21. J. Biol. Chem. 225 (1957) 103–114. [PMID: 13416221]
4.  Kominami, S., Ochi, H., Kobayashi, Y. and Takemori, S. Studies on the steroid hydroxylation system in adrenal cortex microsomes. Purification and characterization of cytochrome P-450 specific for steroid C-21 hydroxylation. J. Biol. Chem. 255 (1980) 3386–3394. [PMID: 6767716]
5.  Martineau, I., Belanger, A., Tchernof, A. and Tremblay, Y. Molecular cloning and expression of guinea pig cytochrome P450c21 cDNA (steroid 21-hydroxylase) isolated from the adrenals. J. Steroid Biochem. Mol. Biol. 86 (2003) 123–132. [DOI] [PMID: 14568563]
6.  Arase, M., Waterman, M.R. and Kagawa, N. Purification and characterization of bovine steroid 21-hydroxylase (P450c21) efficiently expressed in Escherichia coli. Biochem. Biophys. Res. Commun. 344 (2006) 400–405. [DOI] [PMID: 16597434]
[EC 1.14.14.16 created 1961 as EC 1.99.1.11, transferred 1965 to EC 1.14.1.8, transferred 1972 to EC 1.14.99.10, modified 2013, transferred 2015 to EC 1.14.14.16]
 
 
EC 1.14.14.19     
Accepted name: steroid 17α-monooxygenase
Reaction: a C21-steroid + [reduced NADPH—hemoprotein reductase] + O2 = a 17α-hydroxy-C21-steroid + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): steroid 17α-hydroxylase; cytochrome P-450 17α; cytochrome P-450 (P-450 17α,lyase); 17α-hydroxylase-C17,20 lyase; CYP17; CYP17A1 (gene name)
Systematic name: steroid,NADPH—hemoprotein reductase:oxygen oxidoreductase (17α-hydroxylating)
Comments: Requires NADPH and EC 1.6.2.4, NADPH—hemoprotein reductase. A microsomal hemeprotein that catalyses two independent reactions at the same active site - the 17α-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis, and the conversion of the 17α-hydroxylated products via a 17,20-lyase reaction to form androstenedione and dehydroepiandrosterone, leading to sex hormone biosynthesis (EC 1.14.14.32, 17α-hydroxyprogesterone deacetylase). The ratio of the 17α-hydroxylase and 17,20-lyase activities is an important factor in determining the directions of steroid hormone biosynthesis towards biosynthesis of glucocorticoid or sex hormones.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-67-8
References:
1.  Lynn, W.S. and Brown, R.H. The conversion of progesterone to androgens by testes. J. Biol. Chem. 232 (1958) 1015–1030. [PMID: 13549484]
2.  Yoshida, K.-I., Oshima, H. and Troen, P. Studies of the human testis. XIII. Properties of nicotinamide adenine dinucleotide (reduced form)-linked 17α-hydroxylation. J. Clin. Endocrinol. Metab. 50 (1980) 895–899. [DOI] [PMID: 6966286]
3.  Gilep, A.A., Estabrook, R.W. and Usanov, S.A. Molecular cloning and heterologous expression in E. coli of cytochrome P45017α. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species. Biochemistry (Mosc.) 68 (2003) 86–98. [PMID: 12693981]
4.  Kolar, N.W., Swart, A.C., Mason, J.I. and Swart, P. Functional expression and characterisation of human cytochrome P45017α in Pichia pastoris. J. Biotechnol. 129 (2007) 635–644. [DOI] [PMID: 17386955]
5.  Pechurskaya, T.A., Lukashevich, O.P., Gilep, A.A. and Usanov, S.A. Engineering, expression, and purification of "soluble" human cytochrome P45017α and its functional characterization. Biochemistry (Mosc.) 73 (2008) 806–811. [PMID: 18707589]
[EC 1.14.14.19 created 1961 as EC 1.99.1.9, transferred 1965 to EC 1.14.1.7, transferred 1972 to EC 1.14.99.9, modified 2013, transferred 2015 to EC 1.14.14.19]
 
 
EC 1.14.14.32     
Accepted name: 17α-hydroxyprogesterone deacetylase
Reaction: (1) 17α-hydroxyprogesterone + [reduced NADPH—hemoprotein reductase] + O2 = androstenedione + acetate + [oxidized NADPH—hemoprotein reductase] + H2O
(2) 17α-hydroxypregnenolone + [reduced NADPH—hemoprotein reductase] + O2 = 3β-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH—hemoprotein reductase] + H2O
Glossary: androstenedione = androst-4-ene-3,17-dione
Other name(s): C-17/C-20 lyase; 17α-hydroxyprogesterone acetaldehyde-lyase; CYP17; CYP17A1 (gene name); 17α-hydroxyprogesterone 17,20-lyase
Systematic name: 17α-hydroxyprogesterone,NADPH—hemoprotein reductase:oxygen oxidoreductase (17α-hydroxylating, acetate-releasing)
Comments: A microsomal cytochrome P-450 (heme-thiolate) protein that catalyses two independent reactions at the same active site - the 17-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis (EC 1.14.14.19), and the conversion of the 17-hydroxylated products via a 17,20-lyase reaction to form androstenedione and 3β-hydroxyandrost-5-en-17-one, leading to sex hormone biosynthesis. The activity of this reaction is dependent on the allosteric interaction of the enzyme with cytochrome b5 without any transfer of electrons from the cytochrome [2,4]. The enzymes from different organisms differ in their substrate specificity. While the enzymes from pig, hamster, and rat accept both 17α-hydroxyprogesterone and 17α-hydroxypregnenolone, the enzymes from human, bovine, sheep, goat, and bison do not accept the former, and the enzyme from guinea pig does not accept the latter [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 62213-24-5
References:
1.  Gilep, A.A., Estabrook, R.W. and Usanov, S.A. Molecular cloning and heterologous expression in E. coli of cytochrome P45017α. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species. Biochemistry (Mosc.) 68 (2003) 86–98. [PMID: 12693981]
2.  Auchus, R.J., Lee, T.C. and Miller, W.L. Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer. J. Biol. Chem. 273 (1998) 3158–3165. [DOI] [PMID: 9452426]
3.  Mak, P.J., Gregory, M.C., Denisov, I.G., Sligar, S.G. and Kincaid, J.R. Unveiling the crucial intermediates in androgen production. Proc. Natl. Acad. Sci. USA 112 (2015) 15856–15861. [DOI] [PMID: 26668369]
4.  Simonov, A.N., Holien, J.K., Yeung, J.C., Nguyen, A.D., Corbin, C.J., Zheng, J., Kuznetsov, V.L., Auchus, R.J., Conley, A.J., Bond, A.M., Parker, M.W., Rodgers, R.J. and Martin, L.L. Mechanistic scrutiny identifies a kinetic role for cytochrome b5 regulation of human cytochrome P450c17 (CYP17A1, P450 17A1). PLoS One 10:e0141252 (2015). [DOI] [PMID: 26587646]
5.  Bhatt, M.R., Khatri, Y., Rodgers, R.J. and Martin, L.L. Role of cytochrome b5 in the modulation of the enzymatic activities of cytochrome P450 17α-hydroxylase/17,20-lyase (P450 17A1). J. Steroid Biochem. Mol. Biol. (2016) . [DOI] [PMID: 26976652]
[EC 1.14.14.32 created 1976 as EC 4.1.2.30, transferred 2016 to EC 1.14.14.32]
 
 
EC 1.14.15.8     
Accepted name: steroid 15β-monooxygenase
Reaction: progesterone + 2 reduced [2Fe-2S] ferredoxin + O2 = 15β-hydroxyprogesterone + 2 oxidized [2Fe-2S] ferredoxin + H2O
Other name(s): cytochrome P-450meg; cytochrome P450meg; steroid 15β-hydroxylase; CYP106A2; BmCYP106A2
Systematic name: progesterone,reduced-ferredoxin:oxygen oxidoreductase (15β-hydroxylating)
Comments: The enzyme from the bacterium Bacillus megaterium hydroxylates a variety of 3-oxo-Δ4-steroids in position 15β. Ring A-reduced, aromatic, and 3β-hydroxy-Δ4-steroids do not serve as substrates [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Berg, A., Ingelman-Sundberg, M. and Gustafsson, J.A. Purification and characterization of cytochrome P-450meg. J. Biol. Chem. 254 (1979) 5264–5271. [PMID: 109432]
2.  Berg, A., Gustafsson, J.A. and Ingelman-Sundberg, M. Characterization of a cytochrome P-450-dependent steroid hydroxylase system present in Bacillus megaterium. J. Biol. Chem. 251 (1976) 2831–2838. [PMID: 177422]
3.  Lisurek, M., Kang, M.J., Hartmann, R.W. and Bernhardt, R. Identification of monohydroxy progesterones produced by CYP106A2 using comparative HPLC and electrospray ionisation collision-induced dissociation mass spectrometry. Biochem. Biophys. Res. Commun. 319 (2004) 677–682. [DOI] [PMID: 15178459]
4.  Goni, G., Zollner, A., Lisurek, M., Velazquez-Campoy, A., Pinto, S., Gomez-Moreno, C., Hannemann, F., Bernhardt, R. and Medina, M. Cyanobacterial electron carrier proteins as electron donors to CYP106A2 from Bacillus megaterium ATCC 13368. Biochim. Biophys. Acta 1794 (2009) 1635–1642. [DOI] [PMID: 19635596]
5.  Lisurek, M., Simgen, B., Antes, I. and Bernhardt, R. Theoretical and experimental evaluation of a CYP106A2 low homology model and production of mutants with changed activity and selectivity of hydroxylation. ChemBioChem 9 (2008) 1439–1449. [DOI] [PMID: 18481342]
[EC 1.14.15.8 created 2010]
 
 
EC 1.14.99.4     
Accepted name: progesterone monooxygenase
Reaction: progesterone + reduced acceptor + O2 = testosterone acetate + acceptor + H2O
Other name(s): progesterone hydroxylase
Systematic name: progesterone,hydrogen-donor:oxygen oxidoreductase (hydroxylating)
Comments: Has a wide specificity. A single enzyme from ascomycete the Neonectria radicicola (EC 1.14.13.54 ketosteroid monooxygenase) catalyses both this reaction and that catalysed by EC 1.14.99.12 androst-4-ene-3,17-dione monooxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37256-85-2
References:
1.  Rahim, M.A. and Sih, C.J. Mechanisms of steroid oxidation by microorganisms. XI. Enzymatic cleavage of the pregnane side chain. J. Biol. Chem. 241 (1966) 3615–3623. [PMID: 5950688]
[EC 1.14.99.4 created 1972, modified 1999]
 
 
EC 1.14.99.9      
Transferred entry: steroid 17α-monooxygenase, now classified as EC 1.14.14.19, steroid 17α-monooxygenase
[EC 1.14.99.9 created 1961 as EC 1.99.1.9, transferred 1965 to EC 1.14.1.7, transferred 1972 to EC 1.14.99.9, modified 2013, deleted 2015]
 
 
EC 1.14.99.10      
Transferred entry: steroid 21-monooxygenase. Now EC 1.14.14.16, steroid 21-monooxygenase
[EC 1.14.99.10 created 1961 as EC 1.99.1.11, transferred 1965 to EC 1.14.1.8, transferred 1972 to EC 1.14.99.10, modified 2013, deleted 2015]
 
 
EC 1.14.99.12     
Accepted name: androst-4-ene-3,17-dione monooxygenase
Reaction: androstenedione + reduced acceptor + O2 = testololactone + acceptor + H2O
Glossary: androstenedione = androst-4-ene-3,17-dione
testololactone = 3-oxo-13,17-secoandrost-4-eno-17,13-lactone
Other name(s): androstene-3,17-dione hydroxylase; androst-4-ene-3,17-dione 17-oxidoreductase; androst-4-ene-3,17-dione hydroxylase; androstenedione monooxygenase; 4-androstene-3,17-dione monooxygenase
Systematic name: androst-4-ene-3,17-dione-hydrogen-donor:oxygen oxidoreductase (13-hydroxylating, lactonizing)
Comments: Has a wide specificity. A single enzyme from the ascomycete Neonectria radicicola (EC 1.14.13.54, ketosteroid monooxygenase) catalyses both this reaction and that catalysed by EC 1.14.99.4, progesterone monooxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37256-74-9
References:
1.  Prairie, R.L. and Talalay, P. Enzymatic formation of testololactone. Biochemistry 2 (1963) 203–208. [PMID: 13985909]
[EC 1.14.99.12 created 1972, modified 1999]
 
 
EC 1.14.99.14     
Accepted name: progesterone 11α-monooxygenase
Reaction: progesterone + reduced acceptor + O2 = 11α-hydroxyprogesterone + acceptor + H2O
Other name(s): progesterone 11α-hydroxylase
Systematic name: progesterone,hydrogen-donor:oxygen oxidoreductase (11α-hydroxylating)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37256-77-2
References:
1.  Shibahara, M., Moody, J.A. and Smith, L.L. Microbial hydroxylations. V. 11α-Hydroxylation of progesterone by cell-free preparations of Aspergillus ochraceus. Biochim. Biophys. Acta 202 (1970) 172–179. [DOI] [PMID: 5417182]
[EC 1.14.99.14 created 1972]
 
 
EC 4.1.2.30      
Transferred entry: 17α-hydroxyprogesterone aldolase. Now EC 1.14.14.32, 17α-hydroxyprogesterone deacetylase
[EC 4.1.2.30 created 1976, deleted 2016]
 
 
EC 4.2.1.86      
Deleted entry:  16-dehydroprogesterone hydratase (reaction is identical to that of EC 4.2.1.98, 16α-hydroxyprogesterone dehydratase)
[EC 4.2.1.86 created 1989, deleted 2004]
 
 
EC 4.2.1.98     
Accepted name: 16α-hydroxyprogesterone dehydratase
Reaction: 16α-hydroxyprogesterone = 16,17-didehydroprogesterone + H2O
For diagram of reaction, click here
Other name(s): hydroxyprogesterone dehydroxylase; 16α-hydroxyprogesterone dehydroxylase; 16α-dehydroxylase; 16α-hydroxyprogesterone hydro-lyase
Systematic name: 16α-hydroxyprogesterone hydro-lyase (16,17-didehydroprogesterone-forming)
Comments: 16α-Hydroxypregnenolone is also a substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 89287-36-5
References:
1.  Glass, T.L. and Lamppa, R.S. Purification and properties of 16α-hydroxyprogesterone dehydroxylase from Eubacterium sp. strain 144. Biochim. Biophys. Acta 837 (1985) 103–110. [DOI] [PMID: 4052439]
[EC 4.2.1.98 created 1999, modified 2004 (EC 4.2.1.86 created 1989, incorporated 2004)]
 
 


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