ExplorEnz: EC 1.14.15.6

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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-450_scc; C₂₇-side chain cleavage enzyme; cholesterol 20-22-desmolase; cholesterol C_20-22 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, Gene, 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-450_scc. 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]