The apparent loss of cytochrome P-450 associated with metabolic activation of carbon tetrachloride

Abstract

Carbon monoxide inhibited the carbon tetrachloride-induced NADPH oxidation rate. The addition of methylviologen to the incubation mixture under the atmosphere of nitrogen resulted in the enhancement of the reductase activity of microsomes for carbon tetrachloride, as determined by chloroform formation. The addition of methylviologen also enhanced the carbon tetrachloride-induced loss of cytochrome P-450, while the apparent content of cytochrome b5 and the activity of NADPH-cytochrome c reductase remained unchanged. Under a strong inhibition of lipid peroxidation by addition of EDTA, carbon tetrachloride induced a clear loss of cytochrome P-450 to the extent similar to that seen in the absence of EDTA. These results indicate that cytochrome P-450 is directly degraded in association with the reductive metabolism of carbon tetrachloride by cytochrome P-450.