Fate of a terminal olefin with Drosophila microsomes and its inhibitory effects on some P-450 dependent activities.
In vitro bioassays were used to analyze the metabolism of the 11-dodecenoic acid (11-DDNA) by microsomes prepared from Drosophila melanogaster RalDDTR strain. 11-DDNA is metabolized to 11,12-epoxylauric acid (epoxyLA) in a NADPH-dependent way. The microsomal production of epoxyLA reaches a plateau very quickly, suggesting the occurrence of an enzyme inactivation process. After incubation of microsomes with (1-14C)11-DDNA, three proteins of Mr approximately 50 kDa were labeled. 11-DDNA inhibits the microsomal metabolism of lauric acid and 7-ethoxycoumarin in a time and NADPH-dependent process. An inhibition of metabolites generated from DDT and testosterone was also obtained but at higher concentrations. These results are discussed according to the fact that RalDDTR is an insecticide resistant strain characterized as a high metabolizer of the insecticide DDT and also of lauric acid, testosterone, and ethoxycoumarin.
Cuany
A
A
INRA, Laboratoire de Biologie des Invertébrés, Antibes, France.
Helvig
C
C
Amichot
M
M
Pflieger
P
P
Mioskowski
C
C
Salaun
J P
JP
Pauron
D
D
Larroque
C
C
Berge
J B
JB
D000475:Alkenes; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004331:Drosophila melanogaster; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D006900:Hydroxylation; D008861:Microsomes / Q000378:metabolism*; D015394:Molecular Structure; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity; D013739:Testosterone / Q000378:metabolism
D000475:Alkenes; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D013739:Testosterone; C054728:11-dodecenoic acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases