Mt: source and target of ROSFree RadicalsPhospholipidCell MembraneProteinCnUHMitochondrion
Mt: source and target of ROS
Cellularfree radical defenseCompartmentalization:Mostoxidativemetabolism andfree radical productionoccurs at the inner mitochondrial membrane.ProtectiveenzymesSeveral:SOD,catalase,glutathioneperoxidase.2H++02+O2--SOD->02+H202H202+H202--CAT->H20+02Concentrated inthe mitochondria.Antioxidantmolecules
Compartmentalization: • Most oxidative metabolism and free radical production occurs at the inner mitochondrial membrane. Protective enzymes • Several: SOD, catalase, glutathione peroxidase. 2H+ + O2·+ O2· -SOD-> O2 + H2O2 H2O2 + H2O2- -CAT-> H2O + O2 • Concentrated in the mitochondria. Antioxidant molecules Cellular free radical defense
Free radical scavenging systemsTable 10.6 Nature andDistributionof CellularDefenses againstFreeRadicalsLocationTypeNonradicaldecompositionCatalaseCytoplasm,mitochondrialmatrixspaceGlutathioneCytoplasm,mitochondrialmatrixspaceGlutathioneperoxidaseCytoplasmGlutathione-S-transferaseCytoplasmQuenchingofactiveoxygenMnSODMitochondrial innermembraneandmatrixspaceCuZnSODExtracellular,cytoplasmLipophilicagentsCytoplasmicandmitochondrialmembranesVitaminE,carotenoids,flavonoids,ubiquinol,etcPlasma,seraHydrophilicagentsVitamin C, uric acid, bilirubin,albumin,etc.Source:from Lippman(1983)and CamougrandandRigoulet(2001)
Free radical scavenging systems
Evidence for the free radical theory of agingCorrelation between species-specificlevelsof anti-oxidant defenses and lifetime energyexpenditure (Cutler, 1984)Correlationsstrongerbetweenmitochondrial (MnSOD) than cytoplasmic(CuSOD,ZnSOD)defense levels
• Correlation between species-specific levels of anti-oxidant defenses and lifetime energy expenditure (Cutler, 1984). • Correlations stronger between mitochondrial (MnSOD) than cytoplasmic (CuSOD, ZnSOD) defense levels. Evidence for the free radical theory of aging