Oxidation of human low-density lipoprotein by soybean 15-lipoxygenase in combination with copper (II) or met-myoglobin

Vanessa J. O'Leary, Annette Graham, David Stone, Victor M. Darley-Usmar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The enzyme 15-lipoxygenase has been implicated in the oxidation of low- density lipoprotein (LDL) in human atherosclerotic lesions. The biochemical mechanism for this oxidative process is not fully understood, and the interaction of the lipoxygenase-modified lipoprotein with metals or metalloproteins has not been explored. In the present study we have used soybean lipoxygenase to model the interaction of the enzyme with LDL and show that a direct oxygenation of fatty acids occurs, including those esterified to cholesterol, with no lag phase or change in electrophoretic mobility of the LDL particle but with some depletion of α-tocopherol. The enzyme- dependent oxidation may involve propagation through the release of peroxyl radicals from its active site but appears to have no requirement for free iron or copper. When lipoxygenase-treated LDL is exposed to either copper (II) or metMb, a rapid oxidation process occurs, resulting in a marked decrease in resistance to oxidation and an increase in the rate of modification to a form with increased electrophoretic mobility. This effect was not seen if lipoxygenase-treated LDL was oxidized by SIN-1, a peroxynitrite donor that oxidizes LDL with no requirement for endogenous lipid hydroperoxides. We propose that a synergistic interaction may occur between the peroxides inserted into LDL as a consequence of the enzymatic action of lipoxygenase with haem proteins or copper, which decreases the potency of the endogenous antioxidants and enhances oxidation.

Original languageEnglish
Pages (from-to)525-532
Number of pages8
JournalFree Radical Biology and Medicine
Volume20
Issue number4
DOIs
Publication statusPublished - Jan 1996
Externally publishedYes

Keywords

  • Atherosclerosis
  • Free radicals
  • Lipid peroxidation
  • Lipid peroxides
  • Lipoxygenase
  • Low- density lipoprotein
  • Myoglobin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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