Reaction mechanism Glutathione reductase

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graphical representation of overall reaction catalyzed gr



gr catalytic cycle


steps:




reductive half

the action of gr proceeds through 2 distinct half reactions, reductive half mechanism followed oxidative half. in first half, nadph reduces fad present in gsr produce transient fadh anion. anion breaks disulfide bond of cys58 - cys63, forming short lived covalent bond stable charge-transfer complex between flavin , cys63. oxidized nadp+ released , subsequently replaced new molecule of nadph. end of so-called reductive half of mechanism.


oxidative half

in oxidative half of mechanism, cys63 nucleophilically attacks nearest sulfide unit in gssg molecule (promoted his467), creates mixed disulfide bond (gs-cys58) , gs anion. his467 of gsr protonates gs- anion release first molecule of gsh. next, cys58 nucleophilically attacks sulfide of cys58, releasing gs anion, which, in turn, picks solvent proton , released enzyme, thereby creating second gsh. so, every gssg , nadph, 2 reduced gsh molecules gained, can again act antioxidants scavenging reactive oxygen species in cell.








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