Hepatic aminopyrine N-demethylase system: effect of cyanide on microsomal N-demethylase activity.
Cyanide, an inhibitor of many hemoproteins, was shown to affect 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 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. Cyanide complex by aminopyrine was observed by spectrophotometrical and epr spectroscopic methods. These results suggest that aminopyrine and cyanide reciprocally affect binding with cytochrome P-450 and modification by cyanide of aminopyrine binding reaction with the hemoprotein produces an inhibition of N-demethylase activity.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D003486:Cyanides / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003864:Depression, Chemical; D005557:Formaldehyde / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats
D003486:Cyanides; D000632:Aminopyrine; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating