title: Lipid peroxidation in mitochondrial inner membranes. I. An integrative kinetic model.
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 low values (approximately equal 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.
authors.affiliation: Grupo de Bioquímica e Biologia Teóricas, Instituto de Investigação Científica, Bento da Rocha Cabral, Lisboa, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Antunes
authors.forename: A
authors.initials: A
authors.lastname: Salvador
authors.forename: H S
authors.initials: HS
authors.lastname: Marinho
authors.forename: R
authors.initials: R
authors.lastname: Alves
authors.forename: R E
authors.initials: RE
authors.lastname: Pinto
mesh_terms: D002308:Cardiolipins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002308:Cardiolipins; D008054:Lipid Peroxides; D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D014810:Vitamin E; D007501:Iron; D005978:Glutathione; D010100:Oxygen