PROPOSED MECHANISM FOR THE CYTOCHROME P450-CATALYZED CONVERSION OF ALDEHYDES TO HYDROCARBONS IN THE HOUSE-FLY, MUSCA-DOMESTICA

Experiments were performed to elucidate the mechanism of hydrocarbon f ormation in microsomal preparations from the house fly, Musca domestic a. 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-H-3]-(Z)-15-tetracosenal (24:1 aldeh yde). Chemical ionization-gas chromatography-mass spectrometry (CI-GC- MS) analyses of the n-tricosane formed by microsomal preparations from [2,2-H-2(2),2-C-13]- and [3,3-H-2(2),3-C-13]tetracosanoyl-CoA demonst rated that the deuteriums on the 2,2- and 3,3-positions were retained in the conversion to the hydrocarbon product. Likewise, CI-GC-MS analy sis of the Z9-23:Hy formed from [1-H-2]tetracosenal by microsomal prep arations demonstrated that the aldehydic proton on the 1-carbon was tr ansferred to the hydrocarbon product. Hydrogen peroxide, cumene hydrop eroxide, and iodosobenzene were able to support hydrocarbon production from [H-3]24:1 aldehyde in place of O-2 and NADPH for short incubatio n times. From these data, a cytochrome P450 mechanism is proposed in w hich the perferryl iron-oxene, resulting from heterolytic cleavage of the O-O bond of the iron-peroxy intermediate, abstracts an electron fr om the C=O double bond of the carbonyl group of the aldehyde. The redu ced perferryl attacks the 1-carbon of the aldehyde to form a thiyl-iro n-hemiacetal diradical. The latter intermediate can fragment to form a n alkyl radical and a thiyl-iron-formyl radical. The alkyl radical the n abstracts the formyl hydrogen to produce the hydrocarbon and CO2.