Oxidation, Reduction, and Sulfhydryl in Autolysis

Evidence has accumulated both for and against the idea that the control of the autolytic mechanism is in some way directly associated with oxidation-reduction levels in the tissue, and is mediated through sulfhydryl compounds such as glutathione and cysteine. Grassmann and Dyckerhoff first showed the activating effect of -SH and HCN on yeast proteases (1). Shortly after, Waldschmidt-Leitz et al. (2, 3) reported a similar activation of mammalian tissue proteases. They found an activator which increased as autolysis proceeded, and this was later identified as glutathione (4). Both groups of investigators indicated that the effect of -SH compounds was to increase the range of catheptic activity. Thus certain proteins not digested before the addition of -SH, were digested in its presence. Others were digested as well before activation as after. Kleinmann and his associates (5-7) showed activation of tumor proteinases toward gelatin, but failed to detect it when such native proteins as casein, egg albumin, organ proteins, and the proteins of the tissue from which the cathepsin was obtained were used. Abderhalden and his associates likewise were unable to detect activation toward the native and tissue proteins used, but found gelatin more rapidly digested in the presence of reduced glutathione (8). Mayr and Borger (9) showed that HCN increases the catheptic digestion of various proteins, including gelatin, serum albumin, edestin, and Witte’s peptone. Reduced glutathione was more effective, while a combination of glutathione and HCN was the most effective activator found. On the other hand Bierich and Rosenbohm were unable to find activation by reduced glutathione in tumor tissues (10). Voegtlin and Maver (11) showed that tissue autolysis was inhibited by oxygen, while the removal of oxygen by nitrogen gas permitted more extensive autolysis. They were able to correlate these effects with the loss or maintenance of sulfhydryl compounds reacting with nitroprusside. Voegtlin, Maver, and Johnson (12) showed that either protein hydrolysis or synthesis could be produced in an autolyzing tissue hash or by means of papain by properly adjusting the oxygen tension, and that the direction of the reaction was determined by the presence of -SH or -S-S--in the form of reduced or oxidized glutathione. Linderstrom-Lang et al. (13-15) were unable to repeat this demonstration with papain and attributed the results previously reported to concentration of the digests by