The effects and the fate of malononitrile and related compounds in animal tissues

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Abstract
Of a series of compounds, including 11 nitriles and ethyl cyanoacetate only malononitrile, methyl thiocyanate and ethyl thiocyanate gave rise to the formation of cyanide and thiocyanante in presence of tissue homogenates or extracts or had any marked effect on tissue slices. In expts. with tissue slices, malononitrile inhibited respiration, progressively with time, and increased aerobic glycolysis. Its action resembled that of cyanide at a molar concn. 100 times smaller. Thiosulfate antagonized somewhat the effects of cyanide but alleviated those of malononitrile only in the 1st, not in the 2d, hour of the expt. Subcut. injn. of malononitrile (14 mg./kg.) increased the lactic acid content of rat brain after 1-2 hrs., but did not change the concn. of cozymase. The formation of thiocyanate from malononitrile and thiosulfate was highest with liver tissue, lowest with brain and intermediate with kidney. The liver enzyme system is saturated at a concn. of 0.0033 [image] malononitrile and optimum at pH 7.0. It is inhibited by cysteine and glutathione and inactivated by boiling. The sum total of cyanide and thiocyanate formed from malononitrile by enzymically-active tissue prepns. was larger in presence than in absence of thiosulfate. The effect is apparently due mainly to the conversion of cyanide into thiocyanate, thus preventing its disappearance in secondary reactions. The formation of cyanide and thiocyanate from methyl and ethyl thiocyanate seems to be largely due to unspecific, nonenzymic factors. Both substances, at 0.02 [image] concn., cause a 40% inhibition of rhodanase activity. A purified prepn. of rhodanase did not induce any formation of thiocyanate from malononitrile and thiosulfate.