Glutathione, disulfide interchange

Keire, D.A., Strauss, E., Guo, W., Noszal, B., Rabenstein, D.L. Kinetics and equilibria of thiol/disulfide interchange reactions of selected biological thiols and related molecules with oxidized glutathione. J. Org. Chem. 1992, 57, 123-127. 

Glutathione helps to maintain the sulfhydryl groups of proteins in a reduced state. An enzyme, protein-disulfide reductase, catalyzes sulfhydryl disulfide interchanges between glutathione and proteins. The reductase is important in insulin breakdown and may catalyze the reassortment of disulfide bonds during polypeptide chain folding. 

Szajewski RP, Whitesides GM (1980) Rate constants and equilibrium constants for thiol-disulfide interchange reactions involving oxidized glutathione. J Am Chem Soc 102 2011-2026... 

Mercapto Glutathione-agarose, thiolated agarose, Enzacryl polythiol Treatment with dipyridyldisulfide, carbodiimide activation, thiol-disulfide interchange reactions [168,184,185,193,194]... 

Most inhibitors of chymotrypsin and trypsin contain disulfide bonds which are needed to maintain active conformations and configurations. Since thiols are expected to react with inhibitor disulfide bonds via sulfhydryl-disulfide interchange and oxidation-reduction reactions, illustrated in Figure 1, we carried out extensive studies on the ability of cysteine, N-acetylcysteine, and reduced glutathione to synergize heat inactivation of soybean inhibitors. Figures 2 and 3 depict some of our findings. 

Cysteamine has been shown to be effective in removing the lysosomal cystine in cystinosis. The weak base cysteamine tends to distribute within the acidic lysosomal space. A mixed disulfide of cysteamine and cysteine is formed by disulfide interchange and is transported out of the lysosomal space by the carrier for lysine. In cytosol the mixed disulfide is cleaved by reduced glutathione. Early introduction of cysteamine therapy can protect the kidneys from further progression of glomerular destruction. In end-stage renal failure replacement therapy (dialysis, transplantation) becomes necessary. Longterm survival of cystinotic patients is followed by additional late sequelae e.g. distal myopathy, loss of retinal function (blindness), disturbances of memory and other cerebral functions (for review see [3]). 

Sinha and Light (1975) obtained better yield by using trypsinogen and trypsin immobilized on Agarose beads. With 0.2-0.6 mg of protein bound per ml of gel up to 60-70% regeneration yield was obtained in 24 h. Furthermore, the incorrectly folded structures continued to refold when placed in a mixture of reduced and oxidized glutathione to allow disulfide interchange. 

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