The article discusses the role of glutathione (GSH) and ascorbate (vitamin C) in cellular antioxidant systems in animals. GSH is a tripeptide thiol that protects cells from oxygen toxicity and is synthesized in all animal cells. GSH deficiency, induced by a transition-state inhibitor of γ-glutamylcysteine synthetase (BSO), leads to multiorgan failure and death in newborn rats and guinea pigs. However, ascorbate can prevent these effects by sparing GSH. In guinea pigs, which cannot synthesize ascorbate, GSH deficiency causes severe damage, but ascorbate can prevent scurvy and tissue damage. In adult mice, which can synthesize ascorbate, GSH deficiency does not cause death, but leads to lung damage. Ascorbate can spare GSH in these cases as well. GSH and ascorbate work together in the reduction of dehydroascorbate, a form of ascorbate. GSH-dependent reduction of dehydroascorbate is catalyzed by various enzymes, including glutaredoxin and protein disulfide isomerase. GSH also functions in the reduction of reactive oxygen species and as a substrate for GSH peroxidases. Ascorbate is recycled in vivo, and its deficiency leads to scurvy. GSH can spare ascorbate by reducing dehydroascorbate, and ascorbate can spare GSH by preventing its degradation. The interplay between GSH and ascorbate is crucial for cellular survival and function. GSH deficiency leads to oxidative stress, which can cause mitochondrial degeneration and multiorgan failure. Ascorbate can mitigate these effects by reducing dehydroascorbate and protecting cells from oxidative damage. The study highlights the importance of GSH and ascorbate in maintaining cellular reducing power and preventing oxidative damage. The findings suggest that GSH and ascorbate work synergistically to protect cells from oxidative stress, and their interplay is essential for maintaining cellular homeostasis. The article also discusses the implications of these findings for understanding and treating diseases associated with oxidative stress, such as cancer, atherosclerosis, and aging.The article discusses the role of glutathione (GSH) and ascorbate (vitamin C) in cellular antioxidant systems in animals. GSH is a tripeptide thiol that protects cells from oxygen toxicity and is synthesized in all animal cells. GSH deficiency, induced by a transition-state inhibitor of γ-glutamylcysteine synthetase (BSO), leads to multiorgan failure and death in newborn rats and guinea pigs. However, ascorbate can prevent these effects by sparing GSH. In guinea pigs, which cannot synthesize ascorbate, GSH deficiency causes severe damage, but ascorbate can prevent scurvy and tissue damage. In adult mice, which can synthesize ascorbate, GSH deficiency does not cause death, but leads to lung damage. Ascorbate can spare GSH in these cases as well. GSH and ascorbate work together in the reduction of dehydroascorbate, a form of ascorbate. GSH-dependent reduction of dehydroascorbate is catalyzed by various enzymes, including glutaredoxin and protein disulfide isomerase. GSH also functions in the reduction of reactive oxygen species and as a substrate for GSH peroxidases. Ascorbate is recycled in vivo, and its deficiency leads to scurvy. GSH can spare ascorbate by reducing dehydroascorbate, and ascorbate can spare GSH by preventing its degradation. The interplay between GSH and ascorbate is crucial for cellular survival and function. GSH deficiency leads to oxidative stress, which can cause mitochondrial degeneration and multiorgan failure. Ascorbate can mitigate these effects by reducing dehydroascorbate and protecting cells from oxidative damage. The study highlights the importance of GSH and ascorbate in maintaining cellular reducing power and preventing oxidative damage. The findings suggest that GSH and ascorbate work synergistically to protect cells from oxidative stress, and their interplay is essential for maintaining cellular homeostasis. The article also discusses the implications of these findings for understanding and treating diseases associated with oxidative stress, such as cancer, atherosclerosis, and aging.