Polyamine enhances the regeneration of reduced glutathione by the activation of NADP-dependent dehydrogenases in yeast

Effect of polyamine on the regeneration of reduced glutathione (GSH) was analyzed in yeast. Spermine stimulated the reduction of oxidized glutathione in the presence of glucose 6-phosphate or isocitrate in permeabilized yeast cells. Stimulation of GSH formation was due to the enhancement of NADPH (reduced nicotinamide adenine dinucleotide phosphate) supply. Polyamine activated mitochondrial NADP (nicotinamide adenine dinucleotide phosphate)-isocitrate dehydrogenase (EC 1.1.1.42) and cytosolic glucose 6-phosphate dehydrogenase (EC 1.1.1.49) from yeast. Activating action of polyamine was largely the effect on the maximal velocity of these enzymes, and the order of effectiveness as the activators was spermine > spermidine > putrescine. The concentrations of spermine required for 50% activation of the enzymes were about 1-2 mM, values that were within the range of physiological concentrations of spermine. Polyamine can act as an antioxidant by stimulating the regeneration of reduced glutathione, the principal reactive oxygen scavenger, through the activation of cytosolic glucose 6-phosphate dehydrogenase and mitochondrial NADP-isocitrate dehydrogenase as the NADPH-generating enzymes in yeast.