Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: Relevance to neurological disease in humans subsisting on cassava

Neurological disorders have been reported from parts of Africa with protein-deficient populations and attributed to cyanide (CN^-) exposure from prolonged dietary use of cassava, a cyanophoric plant. Cyanide is normally metabolized to thiocyanate (SCN^-) by the sulfur-dependent enzyme rhodanese. However, in protein-deficient subjects where sulfur amino acids (SAA) are low, CN^- may conceivably be converted to cyanate (OCN^-), which is known to cause neurodegenerative disease in humans and animals. This study investigates the fate of potassium cyanide administered orally to rats maintained for up to 4 weeks on either a balanced diet (BD) or a diet lacking the SAAs, L-cystine and L-methionine. In both groups, there was a time- dependent increase in plasma cyanate, with exponential OCN^- increases in SAA-deficient rats. A strongly positive linear relationship between blood CN^- and plasma OCN^- concentrations was observed in these animals. These data are consistent with the hypothesis that cyanate is an important mediator of chronic cyanide neurotoxicity during protein-calorie deficiency. The potential role of thiocyanate in cassava-associated konzo is discussed in relationship to the etiology of the comparable pattern of motor-system disease (spastic paraparesis) seen in lathyrism.