Covalent binding of isoketals to ethanolamine phospholipids

Free Radic Biol Med. 2004 Nov 15;37(10):1604-11. doi: 10.1016/j.freeradbiomed.2004.07.031.


Free radicals have been strongly implicated in the pathogenesis of many human diseases. We previously identified the formation of highly reactive gamma-ketoaldehydes, isoketals, in vivo as products of free radical-induced peroxidation of arachidonic acid. Isoketals react with lysine residues on proteins at a rate that far exceeds that of 4-hydroxynonenal and demonstrate a unique proclivity to crosslink proteins. Hydroxynonenal has been shown to react with aminophospholipids, particularly phosphatidylethanolamine. We explored whether isoketals also react with phosphatidylethanolamine. Using liquid chromatography/electrospray mass spectrometry, we found that isoketals form pyrrole and Schiff base adducts with phosphatidylethanolamine. In addition, the ability of isoketals to covalently modify phosphatidylethanolamine is greater than that of 4-hydroxynonenal. These studies identify in vitro novel isoketal adducts. This provides the basis to explore the formation of isoketal-aminophospholipid adducts in vivo and the biological consequences of the formation of these adducts.

Publication types

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

MeSH terms

  • Aldehydes / chemistry
  • Arachidonic Acid / chemistry*
  • Chromatography, Liquid
  • Cross-Linking Reagents / chemistry*
  • Free Radicals / chemistry*
  • Mass Spectrometry
  • Phosphatidylethanolamines / chemistry*
  • Schiff Bases / chemistry


  • Aldehydes
  • Cross-Linking Reagents
  • Free Radicals
  • Phosphatidylethanolamines
  • Schiff Bases
  • Arachidonic Acid
  • phosphatidylethanolamine
  • 4-hydroxy-2-nonenal