Monofluoroacetic acid (Compound 1080), its pharmacology and toxicology
The molecular mechanism of toxic action of fluoroacetate is analyzed in the perspective of scientific developments of the past 30 years. Stereospecific enzymatic conversion of fluoroacetate via fluoroacetyl-CoA + oxalacetate to (-)-erythrofluorocitrate in mitochondria is the metabolic pathway that converts the nontoxic fluoroacetate to the toxic intracellular effector molecule. The mode of toxic effect of (-)-erythrofluorocitrate cannot be equated with its reversible inhibitory effect on a mitochondrial enzyme (aconitase) as had been originally thought by Peters (1963) and is still propagated in textbooks. Instead, the chemical modification of inner mitochondrial membrane proteins by (-)-erythrofluorocitrate, comprising a novel, as yet incompletely understood biochemical mechanism, is the molecular basis of toxicity. Research in this new area may eventually explain selective (species--dependent) toxicity, the development of resistance to this poison and can lead to the scientific basis of the development of antidotes.