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 presen ce 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 nicotinamid e-adenine dinucleotide phosphate (NADP) to its reduced form (NADPH) by gluc ose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (B-PGD) and (4) reduction of GSSG to GSH by glutathione reductase (GR) usi ng NADPH. The rate of GSH regeneration is thus dependent on the enzymatic a ctivity and concentration of substrate. G-6-PD deficiency and enzyme inhibi tory chemicals reduce GSH regeneration and concentration of substrate great ly influences the rate of GSH regeneration. Not only glucose but also manno se, fructose and galactose may also be used as energy source. Interspecies and intraspecies differences occur in the rate of GSH regeneration. These d ifferences cannot be explained by variations in enzymatic activities. Altho ugh physiological relevance of GSH regeneration is still unclear, it is kno wn that erythrocytes from G-6-PD-deficient patients have lowered erythrocyt e deformability and shortened erythrocyte life-span. In-vitro experiments s how lowered GSH regeneration enforces loss of deformability. These findings suggest that GSH regeneration plays an important role in erythrocyte biolo gy.