Carbon radicals in the metabolism of alkyl hydrazines.
The metabolism of phenelzine (2-phenylethylhydrazine) by rat liver microsomes yields phenylacetaldehyde, 2-phenylethanol, and ethylbenzene. A carbon radical is formed during the oxidative metabolism of phenelzine that reacts with the prosthetic heme of cytochrome P-450 and irreversibly inactivates the enzyme. The radical has been spin-trapped, isolated, and shown by mass spectrometry to be the 2-phenylethyl radical. The metal-free pophyrin derived from the prosthetic heme group has been isolated and identified as N-(2-phenylethyl)protoporphyrin IX. The metabolism of phenelzine, an alkyl hydrazine, thus yields a carbon radical that inactivates cytochrome P-450, is converted to a hydrocarbon by hydrogen atom abstraction, and reacts with spin traps or (presumably) alternative cellular targets.
D000818:Animals; D002849:Chromatography, Gas; D065607:Cytochrome P-450 Enzyme Inhibitors; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010624:Phenelzine / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D005609:Free Radicals; D010624:Phenelzine; D010634:Phenobarbital