ExplorEnz: EC 1.14.14.32

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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, PDB, 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]