Lipid peroxidation generates body odor component trans-2-nonenal covalently bound to protein in vivo

J Biol Chem. 2010 May 14;285(20):15302-15313. doi: 10.1074/jbc.M109.068023. Epub 2010 Mar 8.


trans-2-Nonenal is an unsaturated aldehyde with an unpleasant greasy and grassy odor endogenously generated during the peroxidation of polyunsaturated fatty acids. 2-Nonenal covalently modified human serum albumin through a reaction in which the aldehyde preferentially reacted with the lysine residues. Modified proteins were immunogenic, and a specific monoclonal antibody (mAb) 27Q4 that cross-reacted with the protein covalently modified with 2-nonenal was raised from mouse. To verify the presence of the protein-bound 2-nonenal in vivo, the mAb 27Q4 against the 2-nonenal-modified keyhole limpet hemocyanin was raised. It was found that a novel 2-nonenal-lysine adduct, cis- and trans-N(epsilon)-3-[(hept-1-enyl)-4-hexylpyridinium]lysine (HHP-lysine), constitutes an epitope of the antibody. The immunoreactive materials with mAb 27Q4 were detected in the kidney of rats exposed to ferric nitrilotriacetate, an iron chelate that induces free radical-mediated oxidative tissue damage. Using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry, we also established a highly sensitive method for detection of the cis- and trans-HHP-lysine and confirmed that the 2-nonenal-lysine adducts were indeed formed during the lipid peroxidation-mediated modification of protein in vitro and in vivo. Furthermore, we examined the involvement of the scavenger receptor lectin-like oxidized low density lipoprotein receptor-1 in the recognition of 2-nonenal-modified proteins and established that the receptor recognized the HHP-lysine adducts as a ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / immunology
  • Aldehydes / metabolism*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Chromatography, High Pressure Liquid
  • Immunohistochemistry
  • Kidney / drug effects
  • Kidney / metabolism
  • Lipid Peroxidation*
  • Magnetic Resonance Spectroscopy
  • Male
  • Odorants*
  • Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry


  • Aldehydes
  • Antibodies, Monoclonal
  • Proteins
  • 2-nonenal