Reactivation by dithiols of enzymes inhibited by lewisite.

The protein component of a number of enzyme systems contains SH groups which are either freely reacting or sluggish. The freely reacting SH groups give the nitroprusside test in the native protein, are easily oxidized by mild oxidizing agents and alkylating agents in low concentrations (iodoacetate,mustardgas, diphosgene, cyanogenchloride), and readily form mercaptides. On denaturation, the sluggish SH groups become freely acting. Sulphydryl enzymes are widely distributed, existing among the enzymes concerned with the metabolism of proteins, fats and carbohydrates. Since the metabolism of foodstuffs is performed by a series of enzymic reactions which in some steps are linked to each other, it follows that inhibition of sulphydryl enzymes will create profound disturbances in the metabolism of the body. Inhibition of any of these SH enzymes by oxidizing agents or mercaptideforming agents can be counteracted by addition of thiol compounds. In fact, thiols were used successfully years ago by Voegtlin, Dyer & Leonard (1923), Voegtlin, Rosenthal & Johnson (1931), and by Eagle (1939), in the treatment of arsenical poisoning in animals. Monothiols, however, were often found inefficacious. The introduction of dithiols (Peters, Stocken & Thompson, 1945) has marked a great progress in the reactivation ofSH enzymes inhibited by oxidizing or mercaptide-forming agents, and hence in the treatment of intoxications produced by these substances. This paper is concerned with the inhibition of SH enzymes by lewisite and their reactivation by dithiols.