Free radical pathways in the in vitro hepatic metabolism of phenelzine.
The in vitro metabolism of phenelzine (2-phenylethylhydrazine) by phenobarbital-pretreated rat liver microsomes yields ethylbenzene, 2-phenylethanol, 2-phenylacetaldehyde, benzaldehyde, benzylalcohol, and toluene as metabolites. Isotopic studies demonstrate that the oxygen atom of 2-phenylethanol derives from molecular oxygen and that this alcohol is not produced by reduction of 2-phenylacetaldehyde. The rates of destruction of cytochrome P-450, accumulation of spin-trapped 2-phenylethyl radicals, and formation of ethylbenzene and 2-phenylethanol are the same for [1,1-2H]-2-phenylethylhydrazine as for the undeuterated substrate. Small primary isotope effects are observed, however, for the formation of 2-phenylacetaldehyde (kH/kD greater than 1) and benzaldehyde (kH/kD less than 1). Synthetic 2-phenylethylhydroperoxide is converted by liver microsomes to the same alcohol and aldehyde metabolites. The results indicate that the metabolism of phenelzine by rat liver microsomes proceeds primarily via the 2-phenylethyl radical.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003903:Deuterium; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D010624:Phenelzine / Q000378:metabolism*; D051381:Rats; D013113:Spin Labels; D013329:Structure-Activity Relationship
D005609:Free Radicals; D010545:Peroxides; D013113:Spin Labels; C051393:2-phenylethylhydroperoxide; D003577:Cytochrome P-450 Enzyme System; D003903:Deuterium; D010624:Phenelzine; D010100:Oxygen