IntEnz

EC 1.14.15.6 - Cholesterol monooxygenase (side-chain-cleaving)

IntEnz Enzyme Nomenclature
EC 1.14.15.6

Names

Reaction

• 35739 [IUBMB]
  cholesterol

  cholesterol

  Name origin: UniProt - CHECKED (C)

  CHEBI:16113

  Formula: C27H46O
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

  +

  6

  H⁺

  H(+)

  Name origin: UniProt - CHECKED (C)

  CHEBI:15378

  Formula: H
  Charge: 1

  ChEBI compound status: CHECKED (C)

  

  +

  3

  O₂

  O2

  Name origin: UniProt - CHECKED (C)

  CHEBI:15379

  Formula: O2
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

  +

  6

  reduced [adrenodoxin]

  reduced [adrenodoxin]

  GENERIC:9998

  Is ROOT: no
  ROOT compound: GENERIC:9997

  Number of residues: 1

  [2Fe-2S]1+ [2Fe-2S](1+) Name origin: UniProt - CHECKED (C) CHEBI:33738 Formula: Fe2S2 Charge: 1 Position: undefined ChEBI compound status: CHECKED (C)

  =

  4-methylpentanal

  4-methylpentanal

  Name origin: UniProt - CHECKED (C)

  CHEBI:17998

  Formula: C6H12O
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

  +

  4

  H₂O

  H2O

  Name origin: UniProt - CHECKED (C)

  CHEBI:15377

  Formula: H2O
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

  +

  6

  oxidized [adrenodoxin]

  oxidized [adrenodoxin]

  GENERIC:9999

  Is ROOT: no
  ROOT compound: GENERIC:9997

  Number of residues: 1

  [2Fe-2S]2+ [2Fe-2S](2+) Name origin: UniProt - CHECKED (C) CHEBI:33737 Formula: Fe2S2 Charge: 2 Position: undefined ChEBI compound status: CHECKED (C)

  +

  pregnenolone

  pregnenolone

  Name origin: UniProt - CHECKED (C)

  CHEBI:16581

  Formula: C21H32O2
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

Cofactor

• heme-thiolate

Comments:

A heme-thiolate protein (cytochrome P450). 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

References

1. Burstein, S., Middleditch, B. S., 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: 9028-9037 (1975). [PMID: 1238395]
2. Hanukoglu, I., Spitsberg, V., Bumpus, J. A., Dus, K. M., Jefcoate, C. R.
   Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover.
   J. Biol. Chem. 256: 4321-4328 (1981). [PMID: 7217084]
3. Hanukoglu, I., 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: 27-31 (1986). [PMID: 3011431]
4. Strushkevich, N., MacKenzie, F., Cherkesova, T., Grabovec, I., Usanov, S., Park, H. W.
   Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.
   Proc. Natl. Acad. Sci. U.S.A. 108: 10139-10143 (2011). [PMID: 21636783]
5. Mast, N., Annalora, A. J., Lodowski, D. T., Palczewski, K., Stout, C. D., Pikuleva, I. A.
   Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1.
   J. Biol. Chem. 286: 5607-5613 (2011). [PMID: 21159775]

[EC 1.14.15.6 created 1983, modified 2013, modified 2014]