Although the biological detoxication of cyanide and other nucelophilic xenobiotics with sulfane sulfur is a process of substantial public health importance, its biochemical basis has not yet been eludicated properly. Both in the agrarian tropics, where dietary consumption of cyanogenic glycosides is widespread, and in modern industrial society where frequent exposure to HCN and other nucleophilic pollutants is practically unavoidable, the chronic effects on the populace are obviously deleterious. Yet, the systematic development of nutritional and/or pharmacologic strategies to combat such chronic exposure has lagged because of an inadequate understanding of the biochemical basis of the detoxication process. The long term objectives of the proposed research are to relieve this deficiency by direct biochemical characterization of all components of the cyanide detoxication system and application of the knowledge thus gained to the rational manipulation of cyanide detoxication capacity.
Specific aims of this research include the development of methods for the quantitative reactive sulfur and efforts to alter this sulfane pool in vivo by nutritional and pharmacologic means.
The aims also include establishing the metabolic interrelationships among the enzymes that catalyze reactions of sulfane sulfur in normal metabolism. Special attention will be accorded the newly discovered participation of serum albumin in these processes. Finally, tracer kinetic studies will be employed to examine the flux of sulfane sulfur in vivo as a means of testing the new overall rationale for normal cyanide detoxication in the situation of chronic exposure. The results of these studies are expected to be of importance in the recognition, prevention, and treatment of chronic intoxication with cyanide from nutritional sources (principally the cyanogenic glycosides of cassava, millets and other cyanophoric food and feed plants), from tobacco smoke, and from industrial pollution. These results will also have implications for the toxicology of other xenobiotics that react with sulfur compounds.
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