Metabolism of arylhydrazines by cytochrome P-450 mixed function oxidases and prostaglandin(H)synthase from mouse lungs.
The arylhydrazines 4-methylphenylhydrazine hydrochloride, N'-acetyl-4-methylphenylhydrazine and N'-acetyl-4-hydroxymethylphenylhydrazine (HMPH) were metabolized by ram seminal vesicle prostaglandin(H)synthase (P(H)S) and by cytochrome P-450- and P(H)S-dependent enzymes from mouse lung. Based on the Km-values, the cytochrome P-450 enzymes were the most efficient, suggesting that they would be responsible for the metabolic activation of these compounds in vivo. Cytochrome P-450-dependent metabolism was inhibited by metyrapone and SKF-525A, ruling out the involvement of flavin mono-oxygenase. Agaritine, an arylhydrazide, was poorly metabolized by both systems.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D006834:Hydrazines / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology*; D012669:Seminal Vesicles / Q000201:enzymology; D013329:Structure-Activity Relationship
D006834:Hydrazines; D003577:Cytochrome P-450 Enzyme System; D011451:Prostaglandin-Endoperoxide Synthases; D008797:Metyrapone