HEPATIC AMINOPYRINE N-DEMETHYLASE SYSTEM: EFFECT OF CYANIDE ON MICROSOMAL N-DEMETHYLASE ACTIVITY

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Abstract
Cyanide, an inhibitor of many hemoproteins, affects a number of microsomal drug-metabolizing activities catalyzed by cytochrome P-450. The N-demethylation reaction of aminopyrine was inhibited noncompetitively by this inhibitor in microsomal preparations from rats. The binding reaction of aminopyrine with microsomal cytochrome P-450 was also modified by cyanide, and an abnormal aminopyrine-induced difference spectrum of microsomes appeared when cyanide was added to the reaction mixture. Partial dissociation of cytochrome P-450.cntdot.cyanide complex by aminopyrine was observed by spectrophotometrical and EPR spectroscopic methods. Aminopyrine and cyanide probably reciprocally affect binding with cytochrome P-450 and modification by cyanide of aminopyrine binding reaction with the hemoprotein may produce an inhibition of N-demethylase activity.