Sodium monofluoroacetate metabolism

Ward, P.F.V. and N.S. Huskisson. 1969. The metabolism of fluoroacetate by plants. Biochem. Jour. 113 9P. Wong, D.H., W.E. Kirkpatrick, D.R. King, and J.E. Kinnear. 1992a. Defluorination of sodium monofluoroacetate (1080) by microorganisms isolated from western Australian soils. Soil Biol. Biochem. 24 833-838. Wong, D.H., W.E. Kirkpatrick, D.R. King, and J.E. Kinnear. 1992b. Environmental factors and microbial inoculum size, and their effect on biodefluorination of sodium monofluoroacetate (1080). Soil Biol. Biochem. 9 838-843. 

Compound 1080 (sodium monofluoroacetate) is a very lethal toxicant which acts by blocking the Em-dem-Meyerhoff pathway, thereby depriving vital cells of energy. Eluoroacetate is metabolized to... 

Chi CH et al Clinical presentation and prognostic factors in sodium monofluoroacetate intoxication. J Toxicol Clin Toxicol 1996 34(6) 707-712. [PMID 8941201] (Rotrospectiv review of 38 cases found 18% mortality. H otension, metabolic acidosis, and increased creatinine were important predictors of mortality.)... 

Tsuji, H., Shimizu, H., Dote, T, et al., 2009. Effects of sodium monofluoroacetate on glucose, amino-acid, and fatty-acid metabolism and risk assessment of glucose supplementation. Drug. Chem. Toxicol. 32 (4), 353-361. 

Among the most deadly of simple compounds is sodium fluoroacetate. The LD50 (the dose lethal for 50% of animals receiving it) is only 0.2 mg/kg for rats, over tenfold less than that of the nerve poison diisopropylphosphofluoridate (Chapter 12).a b Popular, but controversial, as the rodent poison "1080," fluoroacetate is also found in the leaves of several poisonous plants in Africa, Australia, and South America. Surprisingly, difluoroacetate HCF2-COO is nontoxic and biochemical studies reveal that monofluoroacetate has no toxic effect on cells until it is converted metabolically in a "lethal synthesis" to 2R,3R-2-fluorocitrate, which is a competitive inhibitor of aconitase (aconitate hydratase, Eq. 13-17).b This fact was difficult to understand since citrate formed by the reaction of fluorooxalo-acetate and acetyl-CoA has only weak inhibitory activity toward the same enzyme. Yet, it is the fluorocitrate formed from fluorooxaloacetate that contains a fluorine atom at a site that is attacked by aconitase in the citric acid cycle. 

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