Jan 1, 1996

Lipid peroxidation in mitochondrial inner membranes. I. An integrative kinetic model

Free Radical Biology & Medicine
F AntunesR E Pinto

Abstract

An integrative mathematical model was developed to obtain an overall picture of lipid hydroperoxide metabolism in the mitochondrial inner membrane and surrounding matrix environment. The model explicitly considers an aqueous and a membrane phase, integrates a wide set of experimental data, and unsupported assumptions were minimized. The following biochemical processes were considered: the classic reactional scheme of lipid peroxidation; antioxidant and pro-oxidant effects of vitamin E; pro-oxidant effects of iron; action of phospholipase A2, glutathione-dependent peroxidases, glutathione reductase and superoxide dismutase; production of superoxide radicals by the mitochondrial respiratory chain; oxidative damage to proteins and DNA. Steady-state fluxes and concentrations as well as half-lives and mean displacements for the main metabolites were calculated. A picture of lipid hydroperoxide physiological metabolism in mitochondria in vivo showing the main pathways is presented. The main results are: (a) perhydroxyl radical is the main initiation agent of lipid peroxidation (with a flux of 10(-7)MS-1); (b) vitamin E efficiently inhibits lipid peroxidation keeping the amplification (kinetic chain length) of lipid peroxidation at lo...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Biochemical Pathway
Phospholipase A2, human
Dioxygen
Tissue Membrane
Hydrogen Peroxide
Glutathione Disulfide
Antioxidants
Peroxidases
Transcription Initiation

About this Paper

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