An analysis of the inhibition of pyruvate oxidation by arsenicals in relation to the enzyme theory of vesication.

Systematic investigations upon -SH groups in an enzyme appear to have been first made upon urease by Hellerman, Perkins & Clark (1933) (see Hellerman, 1937). Some facts as to the action of maleate upon brain tissue have already been published by WeilMalherbe (1938), who quoted earlier literature. He found that 20 mM-maleic acid inhibited the respiration of brain slices in bicarbonate-glucoseRinger by 10-50 %; the inhibition was comparatively small in presence of pyruvate, and it thus appears that the pyruvate oxidase system is even less sensitive in the slice than in the brei. Our facts are consistent with the idea that an -SH group is essential for the activity of this system, and that this group is so activated as to be specially sensitive to maleate. It is still necessary to qualify this by pointing out that the evidence is indirect, because the enzyme concerned has not yet been obtained in pure form; the evidence has been much strengthened by the dithiol theory of Stocken & Thompson (1940-41) (for a brief account see Peters, Stocken & Thompson, 1945). (Recently, Barron & Singer (1945), see also Waters & Stock (1945), have also concluded that the pyruvate oxidase system is specially sensitive to -SH reagents; independently Bacq (1942) has found the -SH fraction in proteins abolished by some vesicants.) SUMMARY 1. Arising from earlier work on chemical warfare agents, and from a research upon antidotes, the sensitivity of the pyruvate oxidase system from brain to some -SH reagents was investigated. 2. The pyruvate oxidase system and the pyruvate dehydrogenase component were much more sensitive to sodium maleate than succinodehydrogenase. Pyruvate dehydrogenase was inactivated by cystine ester and reactivated by cysteine ester. Both these effects are explained by the presence of an essential -SH group in the enzyme concerned.