Peroxidation of liposomal lipids

Edit Schnitzer, Ilya Pinchuk, Dov Lichtenberg*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

124 Scopus citations

Abstract

Free radicals, formed via different mechanisms, induce peroxidation of membrane lipids. This process is of great importance because it modifies the physical properties of the membranes, including its permeability to different solutes and the packing of lipids and proteins in the membranes, which in turn, influences the membranes' function. Accordingly, much research effort has been devoted to the understanding of the factors that govern peroxidation, including the composition and properties of the membranes and the inducer of peroxidation. In view of the complexity of biological membranes, much work was devoted to the latter issues in simplified model systems, mostly lipid vesicles (liposomes). Although peroxidation in model membranes may be very different from peroxidation in biological membranes, the results obtained in model membranes may be used to advance our understanding of issues that cannot be studied in biological membranes. Nonetheless, in spite of the relative simplicity of peroxidation of liposomal lipids, these reactions are still quite complex because they depend in a complex fashion on both the inducer of peroxidation and the composition and physical properties of the liposomes. This complexity is the most likely cause of the apparent contradictions of literature results. The main conclusion of this review is that most, if not all, of the published results (sometimes apparently contradictory) on the peroxidation of liposomal lipids can be understood on the basis of the physico-chemical properties of the liposomes. Specifically: (1) The kinetics of peroxidation induced by an "external" generator of free radicals (e.g. AAPH) is governed by the balance between the effects of membrane properties on the rate constants of propagation (kp) and termination (kt) of the free radical peroxidation in the relevant membrane domains, i.e. in those domains in which the oxidizable lipids reside. Both these rate constants depend similarly on the packing of lipids in the bilayer, but influence the overall rate in opposite directions. (2) Peroxidation induced by transition metal ions depends on additional factors, including the binding of metal ions to the lipid-water interface and the formation of a metal ions-hydroperoxide complex at the surface. (3) Reducing agents, commonly regarded as "antioxidants", may either promote or inhibit peroxidation, depending on the membrane composition, the inducer of oxidation and the membrane/water partitioning. All the published data can be explained in terms of these (quite complex) generalizations. More detailed analysis requires additional experimental investigations.

Original languageEnglish
Pages (from-to)499-515
Number of pages17
JournalEuropean Biophysics Journal
Volume36
Issue number4-5
DOIs
StatePublished - Apr 2007

Funding

FundersFunder number
Lady Davis Chair of Biochemistry
Israel Science Foundation362/02

    Keywords

    • Antioxidants
    • Copper
    • Free radicals
    • Lipids
    • Liposomes
    • Membranes
    • Peroxidation

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