THE CYANIDE INSENSITIVE STEAROYL-COA DESATURASE IN THE HOUSEFLY, MUSCA-DOMESTICA - POSSIBLE INTERACTIONS OF CYTOCHROME-B(5) AND CYTOCHROME-P-450

It is well known that cyanide is toxic to many species of vertebrate animals. However, many different insect groups have a resistance to the effects of cyanide. One of the reactions affected by cyanide is the conversion of stearate to oleate by the acyl-CoA desaturase. At concentrations of cyanide (1-2 mM) which completely inhibit the vertebrate desaturase, we observed that the housefly desaturase was inhibited only 37%. We showed cyanide to be a non-competitive inhibitor of the desaturase. We also have studied the sensitivity of this reaction to other inhibitors, to metal chelators and to free radical scavengers. Data from the free radical scavengers suggested that some form of free radical is involved in desaturation. Piperonyl butoxide and carbon monoxide, inhibitors of cytochrome P-450, resulted in 19% and 29% inhibition, respectively, in the housefly. These compounds did not inhibit the vertebrate desaturase. Combining piperonyl butoxide with cyanide resulted in an additive inhibitory effect. These data suggest that, in the housefly there is an interaction between both cytochrome P-450 and cytochrome b5 and the desaturase which may help to explain the insensitivity of the desaturase to cyanide. Another interpretation of our data suggests the possibility of three forms of the desaturase: one sensitive to cytochrome P-450 inhibitors; one sensitive to cyanide; and one insensitive to cyanide.