Destruction of cytochrome P-450 by ethylene. Structure of the resulting prosthetic heme adduct.
The prosthetic heme of cytochrome P-450 is converted during the metabolism of ethylene into an abnormal hepatic porphyrin. This porphyrin has been isolated, purified, and characterized by field desorption mass spectrometry and 360-MHz nuclear magnetic resonance spectroscopy. It has been unambiguously identified as one of the four possible isomers of N-(2-hydroxyethyl)protoporphyrin IX (isolated as the dimethyl ester). The isomer which is obtained bears the N-alkyl group on one of the two propionic acid-substituted pyrrole rings in the porphyrin. Strong support is provided by the structure of this porphyrin for our contention that the prosthetic heme of cytochrome P-450 is alkylated during attempted transfer of the catalytically-activated oxygen to the pi-bond of destructive unsaturated substrates.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005030:Ethylenes / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D007536:Isomerism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010634:Phenobarbital / Q000494:pharmacology; D011166:Porphyrins / Q000032:analysis*; D011524:Protoporphyrins / Q000032:analysis*; D051381:Rats
D005030:Ethylenes; C029397:N-(2-hydroxyethyl)protoporphyrin IX; D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital