Proposed Mechanism for the Cytochrome P450-catalyzed Conversion of Aldehydes to Hydrocarbons in the House Fly, Musca Domestica

Biochemistry. 1995 Dec 12;34(49):16221-7. doi: 10.1021/bi00049a038.

Abstract

Experiments were performed to elucidate the mechanism of hydrocarbon formation in microsomal preparations from the house fly, Musca domestica. Antibody to both house fly cytochrome P450 reductase and a purified cytochrome P450 (CYP6A1) from the house fly inhibited (Z)-9-tricosene (Z9-23:Hy) formation from [15,16-3H]-(Z)-15-tetracosenal (24:1 aldehyde). Chemical ionization-gas chromatography-mass spectrometry (CI-GC-MS) analyses of the n-tricosane formed by microsomal preparations from [2,2-2H2,2-13C]- and [3,3-2H2,3-13C]tetracosanoyl-CoA demonstrated that the deuteriums on the 2,2- and 3,3-positions were retained in the conversion to the hydrocarbon product. Likewise, CI-GC-MS analysis of the Z9-23:Hy formed from [1-2H]tetracosenal by microsomal preparations demonstrated that the aldehydic proton on the 1-carbon was transferred to the hydrocarbon product. Hydrogen peroxide, cumene hydroperoxide, and iodosobenzene were able to support hydrocarbon production from [3H]24:1 aldehyde in place of O2 and NADPH for short incubation times. From these data, a cytochrome P450 mechanism is proposed in which the perferryl iron-oxene, resulting from heterolytic cleavage of the O-O bond of the iron-peroxy intermediate, abstracts an electron from the C=O double bond of the carbonyl group of the aldehyde. The reduced perferryl attacks the 1-carbon of the aldehyde to form a thiyl-iron-hemiacetal diradical. The latter intermediate can fragment to form an alkyl radical and a thiyl-iron-formyl radical. The alkyl radical then abstracts the formyl hydrogen to produce the hydrocarbon and CO2.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes / metabolism*
  • Animals
  • Catalysis
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Houseflies / enzymology*
  • Hydrocarbons / metabolism*
  • Kinetics
  • Male
  • Pupa
  • Substrate Specificity

Substances

  • Aldehydes
  • Hydrocarbons
  • Cytochrome P-450 Enzyme System