Glutathione, a prosthetic group of glyceraldehyde-3-phosphate dehydrogenase.

It has been reported that glycolysis in mouse brain homogenates is inhibited by ferrous sulfate (1). It was shown that the inhibition is due to an iron-activated factor (IF) in brain and is localized at the stage of triose phosphate oxidation. Later, it was found that glyceraldehyde-3-phosphate dehydrogenase, the triose phosphate-oxidizing enzyme, could be protected by the addition of small amounts of glutathione (2). Further studies which will be presented in this paper revealed that glyceraldehyde-3phosphate dehydrogenase contains glutathione as a prosthetic group. The evidence available indicates that inhibition of glycolysis by ferrous sulfate is due to inactivation of the glutathione of glyceraldehyde-3-phosphate dehydrogenase. Protection and Restoration of Glycolysis by Glutathione-Glutathione, as well as esters and amides of some amino acids, protects glycolysis against the iron-activated IF in brain. Once IF has been permitted to act, addition of the amino acid esters or amides has no effect (2). It has now been found that glutathione in addition to its protective action is capable of restoring glycolysis. This is demonstrated in Fig. 1. It was found that other SH compounds, such as cysteine and thioglycolic acid, were also capable of reactivating the enzyme when used in high concentrations, but, unlike glutathione, they had no protective action against IF when used in low concentrations. This difference in the behavior of the sulfhydryl compounds suggested that glutathione has a more specific relationship to glyceraldehyde-3-phosphate dehydrogenase than the other SH compounds. It was therefore postulated that glutathione or a closely related compound is a prosthetic group of glyceraldehyde-3-phosphate dehydrogenase and that IF inactivates the bound prosthetic group. Since proteolytic enzymes were shown to act in a manner similar to IF (2) and amino acid derivatives protected the dehydrogenase, a proteolytic cleavage of the prosthetic group was considered the most likely mechanism to account for these observations. It was therefore assumed that the prosthetic sufhydryl com-