Glutathione regeneration in mammalian erythrocytes

Glutathione (GSH) regeneration is a process in which cells reduce oxidised glutathione (GSSG) to GSH after exposure of cells to oxidants in the presence of suitable energy source such as glucose. This reaction consists of (1) membrane glucose transport, (2) phosphorylation of glucose by hexokinase (HK) utilising adenosine 5'-triphosphate (ATP), (3) reduction of nicotinamide-adenine dinucleotide phosphate (NADP) to its reduced form (NADPH) by glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (B-PGD) and (4) reduction of GSSG to GSH by glutathione reductase (GR) using NADPH. The rate of GSH regeneration is thus dependent on the enzymatic activity and concentration of substrate. G-6-PD deficiency and enzyme inhibitory chemicals reduce GSH regeneration and concentration of substrate greatly influences the rate of GSH regeneration. Not only glucose but also mannose, fructose and galactose may also be used as energy source. Interspecies and intraspecies differences occur in the rate of GSH regeneration. These differences cannot be explained by variations in enzymatic activities. Although physiological relevance of GSH regeneration is still unclear, it is known that erythrocytes from G-6-PD-deficient patients have lowered erythrocyte deformability and shortened erythrocyte life-span. In-vitro experiments show lowered GSH regeneration enforces loss of deformability. These findings suggest that GSH regeneration plays an important role in erythrocyte biology.