IMPORTANCE OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE IN THE ADAPTIVE RESPONSE TO HYDROGEN-PEROXIDE IN SACCHAROMYCES-CEREVISIAE

Glucose-6-phosphate dehydrogenase (G6PDH)-deficient cells of Saccharom yces cerevisiae showed increased susceptibility and were unable to ind uce adaptation to oxidative stress. Historically, mainly in human eryt hrocytes, it has been suggested and accepted that decreased cellular G SH, due to loss of the NADPH-dependent activity of glutathione reducta se (GR), is responsible for the increased sensitivity to oxidative str ess in G6PDH-deficient cells. In the present study we investigated whe ther the increased susceptibility and the inability to induce adaptati on to H2O2 stress of G6PDH-deficient yeast is caused by incompleteness of glutathione recycling. We constructed G6PDH- and GR-deficient muta nts and analysed their adaptive response to H2O2 stress. Although G6PD H-deficient cells contained comparable amounts of GSH and GR activity to wild-type cells, GSSG was not reduced efficiently, and intracellula r GSSG levels and the ratio of GSSG to total glutathione (GSSG/tGSH) w ere higher in G6PDH-deficient cells than in wild-type. On the other ha nd, GR-deficient cells showed a susceptibility identical with that of wild-type cells and induced adaptation to H2O2 stress, even though the GSSG/tGSH ratio in GR-deficient cells was higher than in G6PDH-defici ent cells. These results indicate that incompleteness of glutathione r ecycling alone is not sufficient to account for the increased sensitiv ity and inability to induce adaptation to H2O2 stress of G6PDH-deficie nt yeast cells. In S. cerevisiae, G6PDH appears to play other importan t roles in the adaptive response to H2O2 stress besides supplying NADP H to the GR reaction.