Glutathione

GLUTATHIONE, a dipeptide of cysteine and glutamic acid (cysteinyl-glutamic acid) COOH-CH.NH₂-CH₂-CH₂-CO-NH-CH-CH₂-SH. Glutathione was discovered by Hopkins in 1921 and isolated by him from yeast, liver, and muscle. It was synthetically obtained by Tunnicliffe. Like other compounds containing a sulfhydryl group (SH), e.g., cystine, thioglycolic acid, etc., glutathione easily gives up the H of this group, whereby two molecules of glutathione combine into a molecule of cystine-dipeptide; such oxidized glutathione, in turn, can take H from other compounds, breaking down again into two molecules of reduced glutathione: 2G-SH -> G-S-S-G + H₂ (sulfhydryl form).

The disulfide form (G denotes the glutathione radical). Thus, the reaction represented by this equation is completely reversible and proceeds in one direction or the other depending on the environmental conditions; the active reaction [pH] has an undoubtedly important, but not yet fully clarified, significance in this. Reduced glutathione (GSH) easily gives up its H both to various acceptors (see) and (which is especially important) to molecular O₂. Thus, by taking H from organic compounds and then oxidizing it at the expense of molecular oxygen, glutathione is an important factor in tissue respiratory processes, causing the oxidation of such compounds that do not oxidize by themselves with atmospheric oxygen. The entire course of the process can be represented as follows: RH₂ + G-S-S-G -> R + 2 GSH; 2 GSH + O₂ -> G-S-S-G + H₂O₂; the resulting H₂O₂ is either decomposed by catalase found in all tissues or can serve for other oxidative processes.

In the form of the disulfide form (GS-SG), glutathione is a white amorphous powder, easily soluble in water with an acidic reaction to litmus. Glutathione has not been found in blood serum and plasma; it is contained in erythrocytes and in small quantities in rapidly growing cancerous tumors. In muscles, it is about 0.04%, in the liver up to 0.24%, in yeast 0.18%. For its detection and approximate quantitative estimation, the nitroprusside reaction characteristic of the SH group is used: the test substance is boiled in a few cubic centimeters of water acidified with acetic acid, cooled, an excess of powdered ammonium sulfate is added, 2-3 drops of a freshly prepared 5% solution of sodium nitroprusside Na₂[Fe(CN)₅NO] and a little strong ammonia solution. In the presence of glutathione, a red-violet coloration is obtained. A more accurate quantitative determination is based on iodometric titration.