IN-VITRO INHIBITION OF GLUTATHIONE-REDUCTASE BY ARSENOTRIGLUTATHIONE

-Arsenotriglutathione, a product of the reaction of arsenate or arseni te with glutathione, is a mixed-type inhibitor (K-i = 0.34 mM) of the in vitro reduction of glutathione disulfide by purified yeast glutathi one reductase. Notably, arsenotriglutathione was a 10-fold more potent inhibitor than either arsenite or glutathione. The inhibition of glut athione reductase by arsenotriglutathione was partly reversed by the a ddition of meso-2,3-dimercaptosuccinic acid (DMSA). However, high conc entrations of DMSA also inhibited the reduction of glutathione disulfi de by the yeast enzyme (IC50 of 7 mM with 0.1 mM glutathione disulfide ). Ultrafiltration of the enzyme-arsenotriglutathione complex recovere d about 74% of the original (non-inhibited) activity, suggesting that the inhibition of glutathione reductase by arsenotriglutathione had bo th reversible and irreversible components. The relatively high potency of arsenotriglutathione as an inhibitor of glutathione reductase may alter the reduction of glutathione disulfide and affect the availabili ty of glutathione that is required for the reduction of arsenate to ar senite and for the formation of the arsenotriglutathione complex.