Inactivation of hepatic cytochrome P-450 by allenic substrates

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Abstract

Hepatic microsomal cytochrome P-450 from phenobarbital-pretreated rats is destroyed by 17-α-propadienyl-19-nortestosterone, 1-propadienylcyclohexanol, and 1,1-dimethylallene. Substantial activity is also exhibited by 1-propadienylcyclohexanol against the enzymes in microsomes from 3-methylcholanthrene pretreated rats. The destructive process requires NADPH, is not inhibited by glutathione, and is paralleled by equimolar loss of hepatic heme but not by invivo accumulation of identifiable “green” pigments. Attempted metabolism of allenes can thus result in destruction of cytochrome P-450.

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