Publication Type |
Journal Article |
Title |
Lipid peroxidation in mitochondrial inner membranes .1. An integrative kinetic model |
Authors |
F. J. N. Antunes A Salvador H. Susana Marinho R Alves RE Pinto |
Groups |
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Journal |
FREE RADICAL BIOLOGY AND MEDICINE |
Year |
1996 |
Month |
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Volume |
21 |
Number |
7 |
Pages |
917-943 |
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 A(2), 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 low values (congruent to 10); (c) only a very minor fraction of lipid hydroperoxides escapes reduction via glutathione-dependent peroxidases; (d) oxidized glutathione is produced mainly from the reduction of hydrogen peroxide and not from the reduction of lipid hydroperoxides. Copyright (C) 1996 Elsevier Science Inc. |
DOI |
http://dx.doi.org/10.1016/S0891-5849(96)00185-2 |
ISBN |
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Publisher |
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Book Title |
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ISSN |
0891-5849 |
EISSN |
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Conference Name |
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Bibtex ID |
ISI:A1996VP99800002 |
Observations |
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