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 prolon ged dietary use of cassava, a cyanophoric plant. Cyanide is normally metabo lized to thiocyanate (SCN-) by the sulfur-dependent enzyme rhodanese. Howev er, in protein-deficient subjects where sulfur amino acids (SAA) are low, C N- may conceivably be converted to cyanate (OCN-), which is known to cause neurodegenerative disease in humans and animals. This study investigates th e fate of potassium cyanide administered orally to rats maintained for up t o 4 weeks on either a balanced diet (BD) or a diet lacking the SAAs, L-cyst ine and L-methionine. In both groups, there was a time-dependent increase i n plasma cyanate, with exponential OCN- increases in SAA-deficient rats. A strongly positive linear relationship between blood CN- and plasma OCN- con centrations was observed in these animals. These data are consistent with t he hypothesis that cyanate is an important mediator of chronic cyanide neur otoxicity during protein-calorie deficiency. The potential role of thiocyan ate in cassava-associated konzo is discussed in relationship to the etiolog y of the comparable pattern of motor-system disease (spastic paraparesis) s een in lathyrism.