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

John Tor-Agbidye, Valerie S. Palmer, Michael R. Lasarev, A. Morrie Craig, Linda L. Blythe, Mohammad I. Sabri, Peter S. Spencer

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalToxicological Sciences
Volume50
Issue number2
DOIs
StatePublished - Sep 6 1999

Keywords

  • Cassava
  • Cyanate
  • Cyanide
  • Metabolism
  • Neurodegenerative disease
  • Sulfate
  • Sulfur amino acid deficiency
  • Thiocyanate

ASJC Scopus subject areas

  • Toxicology

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