Destruction of cytochrome P-450 by ethylene. Structure of the resulting prosthetic heme adduct

J Biol Chem. 1981 May 10;256(9):4395-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism*
  • Ethylenes* / metabolism*
  • Heme / metabolism*
  • Isomerism
  • Liver / drug effects
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Phenobarbital / pharmacology
  • Porphyrins / analysis*
  • Protoporphyrins / analysis*
  • Rats

Substances

  • Ethylenes
  • N-(2-hydroxyethyl)protoporphyrin IX
  • Porphyrins
  • Protoporphyrins
  • Heme
  • Cytochrome P-450 Enzyme System
  • Phenobarbital