Influence of two haloalkanes on the redox behavior of hepatic microsomal cytochrome b-5 and its possible relationship to stearate desaturase.
The possible interaction of two haloalkanes - bromotrichloromethane and 1,2-dibromo-1,2-dichlorethane - with stearate desaturase was assessed in hepatic microsomes from rats fed a high carbohydrate diet which elevates the levels of stearate desaturase. Both compounds shifted the redox steady state of NADPH reduced hepatic microsomal cytochrome b-5 towards ferricytochrome b-5 and enhanced the re-oxidation of NADH reduced hepatic microsomal cytochrome b-5. The equilibrium constants for the enhancement of microsomal electron transfer by the haloalkanes in these preparations were 2.2 +/- 0.3 mM and 0.46 +/- 0.1 mM for bromotrichloromethane and 1,2-dibromo-1,2-dichlorethane, respectively. The haloalkane mediated enhancement of the oxidation of cytochrome b-5 in hepatic microsomes from rats fed a high carbohydrate diet was diminished by KCN and the inhibitors of cytochrome P-450, CO and/or metyrapone, as well as by fasting of the experimental animals. The I50 values for KCN inhibition of the effects of the haloalkanes on the re-oxidation of cytochrome b-5 (01 mM) were identical to the I50 for KCN inhibition of stearate desaturase (Oshino et al., 1966). The haloalkanes did not affect the activity of hepatic microsomal NADH- or NADPH-cytochrome c reductase, the autoxidation of purified trypsin-cleaved ferrocytochrome b-5 or the conversion of stearoyl CoA to oleate. It is concluded that bromotrichloromethane and 1,2-dibromo-1,2-dichloroethane stimulate hepatic microsomal electron transfer from NADH via cytochrome b-5 by interacting with cytochrome P-450 and with stearate desaturase.
D000818:Animals; D001975:Bromotrichloromethane / Q000494:pharmacology*; D002725:Chloroform / Q000031:analogs & derivatives*; D003580:Cytochromes / Q000378:metabolism*; D015786:Cytochromes b5; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology*; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism*; D009243:NAD; D010084:Oxidation-Reduction; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*
D003580:Cytochromes; D006846:Hydrocarbons, Halogenated; D009243:NAD; C033164:1,2-dibromo-1,2-dichloroethane; D002725:Chloroform; D015786:Cytochromes b5; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; D001975:Bromotrichloromethane; D011190:Potassium Cyanide