High pressure induced inactivation of ferrous cytochrome P-450 LM2 (IIB4) CO complex: evidence for the presence of two conformers in the oligomer

Biochem Biophys Res Commun. 1992 Oct 15;188(1):216-21. doi: 10.1016/0006-291x(92)92372-5.

Abstract

The effect of high pressure on the spectral properties of cytochrome P-450 LM2(Fe2+)-CO complex was studied. The application of high pressure was shown to induce the conversion of cytochrome P-450 to P-420. In the solution when P-450 was oligomeric only about 65% of the total converted to P-420. The remaining portion of cytochrome P-450 was stable at pressures up to 6 kbar. When P-450 was incorporated into membranes or when it was succinylated, the proportion of the pressure sensitive fraction was slightly higher (about 75%). Dissociation of P-450 oligomers into monomers was made by addition of 0.2% Triton N-101. Monomers were the most sensitive to pressure; they could be completely converted to P-420. These results have been interpreted as evidence for the existence of two different conformers of P-450 LM2, which differ in pressure stability. Splitting between these two states appears to be a result of the oligomeric organization of cytochrome P-450 in solution and in the membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Carbon Monoxide / metabolism*
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / chemistry
  • Liposomes
  • Liver / drug effects
  • Liver / enzymology
  • Phenobarbital / pharmacology
  • Pressure
  • Protein Conformation
  • Proteolipids / chemistry
  • Proteolipids / metabolism
  • Rabbits
  • Spectrophotometry
  • Steroid Hydroxylases / antagonists & inhibitors*
  • Steroid Hydroxylases / chemistry
  • Thermodynamics

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Liposomes
  • Proteolipids
  • proteoliposomes
  • Carbon Monoxide
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • steroid 15-alpha-hydroxylase
  • Phenobarbital