AMINO ACID-DEPENDENT REGULATION OF THE SACCHAROMYCES-CEREVISIAE GSH1 GENE BY HYDROGEN-PEROXIDE

The tripeptide gamma-L-glutamyl-L-cysteinylglycine (glutathione) is on e of the major antioxidant molecules of cells and plays a vital role i n buffering the cell against reactive oxygen species and toxic electro philes. In the yeast Saccharomyces cerevisiae, the first enzyme involv ed in glutathione biosynthesis, gamma-glutamylcysteine synthetase, is encoded by the GSH1 gene. This study shows that the regulation of the yeast GSH1 gene by oxidants and the heavy metal cadmium is at the leve l of transcription. We also demonstrate that the regulation of the GSH 1 gene by H2O2 depends upon the presence of the amino acids glutamate, glutamine and lysine in the media. Moreover, regulation of the GSH1 g ene by H2O2, although requiring the Yap1 protein, appears to be mediat ed by a mechanism distinct from that which regulates the Yap1-dependen t induction of genes encoding thioredoxin (TRX2) and a stress-inducibl e HSP70 (SSA1) by H2O2.