Menadione-glutathione conjugate

J. Mauzeroll and A.J. Bard, Scanning electrochemical microscopy of menadione-glutathione conjugate export from yeast cells, Proceedings of the National... 

As already discussed in chapter 4, reactive intermediates can react with reduced GSH either by a direct chemical reaction or by a GSH transferase-mediated reaction. If excessive, these reactions can deplete the cellular GSH. Also, reactive metabolites can oxidize GSH and other thiol groups such as those in proteins and thereby cause a change in thiol status. When the rate of oxidation of GSH exceeds the capacity of GSH reductase, then oxidized glutathione (GSSG) is actively transported out of the cell and thereby lost. Thus, reduced GSH may be removed reversibly by oxidation or formation of mixed disulfides with proteins and irreversibly by conjugation or loss of the oxidized form from the cell. Thus, after exposure of cells to quinones such as menadione, which cause oxidative stress, GSH conjugates, mixed disulfides, and GSSG are formed, all of which will reduce the cellular GSH level. 

FIGURE 14.1 The stractures of glutathione and its conjugate, Af-acetylcysteine and its conj ugate, (25,3ff)-3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1 -ylethoxy)phenyl]-2,3-dihy-dro-l,4-benzoxathiin-6-ol (A) and its bis-cyano adduct (B), (25,3/f)-(-I-)-3-(3-hydro-xyphenyl)-2-[4-(2-pyrrolidin-l-ylethoxy)-phenyl]-2,3-dihydro-l,4-benzoxathiin-6-ol (C) and its JV-acetylcysteine adduct (D), dansyl glutathione, /f-(-t )-pulegone, menadione, and iodoacetamide. 

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