Enzyme systems Antioxidant

enzymatic pathway detoxification of reactive oxygen species.

as chemical antioxidants, cells protected against oxidative stress interacting network of antioxidant enzymes. here, superoxide released processes such oxidative phosphorylation first converted hydrogen peroxide , further reduced give water. detoxification pathway result of multiple enzymes, superoxide dismutases catalysing first step , catalases , various peroxidases removing hydrogen peroxide. antioxidant metabolites, contributions of these enzymes antioxidant defenses can hard separate 1 another, generation of transgenic mice lacking 1 antioxidant enzyme can informative.

superoxide dismutase, catalase, , peroxiredoxins

superoxide dismutases (sods) class of closely related enzymes catalyze breakdown of superoxide anion oxygen , hydrogen peroxide. sod enzymes present in aerobic cells , in extracellular fluids. superoxide dismutase enzymes contain metal ion cofactors that, depending on isozyme, can copper, zinc, manganese or iron. in humans, copper/zinc sod present in cytosol, while manganese sod present in mitochondrion. there exists third form of sod in extracellular fluids, contains copper , zinc in active sites. mitochondrial isozyme seems biologically important of these three, since mice lacking enzyme die after birth. in contrast, mice lacking copper/zinc sod (sod1) viable have numerous pathologies , reduced lifespan (see article on superoxide), while mice without extracellular sod have minimal defects (sensitive hyperoxia). in plants, sod isozymes present in cytosol , mitochondria, iron sod found in chloroplasts absent vertebrates , yeast.

catalases enzymes catalyse conversion of hydrogen peroxide water , oxygen, using either iron or manganese cofactor. protein localized peroxisomes in eukaryotic cells. catalase unusual enzyme since, although hydrogen peroxide substrate, follows ping-pong mechanism. here, cofactor oxidised 1 molecule of hydrogen peroxide , regenerated transferring bound oxygen second molecule of substrate. despite apparent importance in hydrogen peroxide removal, humans genetic deficiency of catalase — acatalasemia  — or mice genetically engineered lack catalase completely, suffer few ill effects.

decameric structure of ahpc, bacterial 2-cysteine peroxiredoxin salmonella typhimurium.

peroxiredoxins peroxidases catalyze reduction of hydrogen peroxide, organic hydroperoxides, peroxynitrite. divided 3 classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; , 1-cysteine peroxiredoxins. these enzymes share same basic catalytic mechanism, in redox-active cysteine (the peroxidatic cysteine) in active site oxidized sulfenic acid peroxide substrate. over-oxidation of cysteine residue in peroxiredoxins inactivates these enzymes, can reversed action of sulfiredoxin. peroxiredoxins seem important in antioxidant metabolism, mice lacking peroxiredoxin 1 or 2 have shortened lifespan , suffer hemolytic anaemia, while plants use peroxiredoxins remove hydrogen peroxide generated in chloroplasts.

thioredoxin , glutathione systems

the thioredoxin system contains 12-kda protein thioredoxin , companion thioredoxin reductase. proteins related thioredoxin present in sequenced organisms. plants, such arabidopsis thaliana, have particularly great diversity of isoforms. active site of thioredoxin consists of 2 neighboring cysteines, part of highly conserved cxxc motif, can cycle between active dithiol form (reduced) , oxidized disulfide form. in active state, thioredoxin acts efficient reducing agent, scavenging reactive oxygen species , maintaining other proteins in reduced state. after being oxidized, active thioredoxin regenerated action of thioredoxin reductase, using nadph electron donor.

the glutathione system includes glutathione, glutathione reductase, glutathione peroxidases, , glutathione s-transferases. system found in animals, plants , microorganisms. glutathione peroxidase enzyme containing 4 selenium-cofactors catalyzes breakdown of hydrogen peroxide , organic hydroperoxides. there @ least 4 different glutathione peroxidase isozymes in animals. glutathione peroxidase 1 abundant , efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 active lipid hydroperoxides. surprisingly, glutathione peroxidase 1 dispensable, mice lacking enzyme have normal lifespans, hypersensitive induced oxidative stress. in addition, glutathione s-transferases show high activity lipid peroxides. these enzymes @ particularly high levels in liver , serve in detoxification metabolism.