Cyanide Excretion in the Rat

Abstract

MUCH is now known about the body's metabolism of cyanide within a pattern of normal physiology. The conversion of cyanide to thiocyanate was first demonstrated in 1894 ¹ and the enzymatic nature of this reaction was investigated in 1933 ²). The enzyme system was named ‘rhodanese’ and it has been found to be specific for free cyanide without action on organically bound cyano groups. This property indicates that the excretion of thiocyanates after the administration of organic nitriles results not from a direct action on the nitrile itself, but from hydrogen cyanide which had first been removed from the nitrile molecule by another mechanism. Although this rhodanese/thiocyanate excretory pathway is considered to be the primary factor in the detoxification of cyanide there undoubtedly exist other pathways by which this may be mediated or assisted³. These implicate one-carbon compounds and also reveal that the radiocarbon of Na¹⁴CN appears in the methyl groups of choline and methionine and in the ureide carbons of allantoin. Some of it also finds its way into the cyano group of cyanocobalamin. It is known that hydroxocobalamin takes up cyanide avidly to form cyanocobalamin and can protect the experimental animal against lethal doses⁴. Latterly, a further pathway in the detoxification of cyanide has been implicated⁵. This shows that cyanide can combine with cystine in vitro to form 2-iminothiazolidine-4-carboxylic acid and that the formation of this acid also occurs in vivo. On injection of potassium cyanide subcutaneously into rats, the acid can be isolated from the urine in quantities corresponding to 15 per cent of the dose, although the main excretory product (80 per cent of the dose) is thiocyanate.