Monofluoroacetic acid (Compound 1080), its pharmacology and toxicology
- Author(s): Kun, Ernest
- et al.
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.