Fluoroacetate poisoning

Tourtellotte, W.W. and J.M. Coon. 1950. Treatment of fluoroacetate poisoning in mice and dogs. Jour. Pharmacol. Exper. Therapeut. 101 82-91. 

Fluoroethanol, in contrast to ethanol, is only weakly oxidized by purified alcohol dehydrogenases, the rate being one-tenth to one-twentieth. Nevertheless, this rate appears sufficient to produce a typical fluoroacetate poisoning. A fairly long lag period in the development of the fluoroacetate symptoms possibly masks the time required for oxidation of fluoroethanol. 

Cause of fluoroacetate poisoning In 1947 Bartlett and Barron,1 using tissue slice, showed that fluoroacetate blocked the oxidation of acetate competitively, and that this accounted for the toxic effect, namely, the body was deprived of acetate. Liebig and Peters then found that fluoroacetate blocked the oxidation of fumarate in a guinea-pig s kidney homogenate without accumulation of acetate hence Bartlett and Barron s hypothesis could not be the whole story. 

The above observations, taken together with the facts set out on pp. 133-6, support the view that fluoroacetate poisoning is brought about by the building up of FCH2COOH into fluorocitrate by enzymes in vivo. 

The protective effect against fluoroacetate poisoning by C2-containing compounds (see Chenoweth s work, pp. 132 and... 

A retrospective study of 38 cases of sodium fluoroacetate poisoning (including 7 deaths) concluded that hypotension and early-onset metabolic acidosis and increased serum creatinine were most often associated with poor short-term survival. ... 

Gregg K, Hamdorf B, Henderson K, Kopecny J, Wong C (1998) Genetically Modified Ruminal Bacteria Protect Sheep from Fluoroacetate Poisoning. Appl Environ Microbiol 64 3496... 

Buffa, P., Peters, R.A. (1950). The in vivo formation of citrate induced by fluoroacetate poisoning and its significance. J. Physiol. 110 488-500. 

Buffa, P., Guarriero-Bobyleva, V., Pasquali-Ronchetti, J. (1972). Biochemical effects of fluoroacetate poisoning in rat liver. In Carbone-Fluorine Compounds, pp. 303-30. Associated Scientific Compounds, Amsterdam. 

Peters, R.A., Wakelin, R.W. (1953). Fluoroacetate poisoning comparison of syntetic fluorocitric acid with the enzymi-cally synthesized fluorotricarboxylic acid. Nature 171 1111-12. 

Pridmore, S.A. (1978). Fluoroacetate poisoning nine years later. Med. J. Aust. 2 269-70. 

Sherley, M. (2004). The traditional categories of fluoroacetate, poisoning signs and symptoms belie substantial underlying similarities. Toxicol. Lett. 151 399-406. 

Taitelman, U., Roy (Shapira), A., Raikhlin-Eisenkraft, B., Hoffer, E. (1983a). The effect of monoacetin and calcium chloride on acid-base balance and survival in experimental sodium fluoroacetate poisoning. Arch. Toxicol. Suppl. 6 222-1. 

Tourtelotte, W.W., Coon, J.M. (1949). Synergistic effect of sodium acetate and ethanole in antagonizing sodium fluoroacetate poisoning in mice. Fed. Proc. 8 339-50. 

Trabes, J., Rason, N., Avrahami, E. (1983). Computed tomography demonstration of brain damage due to acute sodium mono-fluoroacetate poisoning. J. Toxicol. Clin. Toxicol. 20 85-92. 

Acute fluoroacetate poisoning can result in nausea, vomiting, cardiac arrhythmia, cyanosis, generalized convulsions, hypotension, and death from ventricular fibrillation or respiratory failure. Residual effects are uncommon if the patient survives the acute toxicity. 

Fluoroacetate has been used as a rat poison and can be fatal when eaten by humans. Patients with fluoroacetate poisoning accumulate citrate and fluorocitrate within the cells. What enzyme is inhibited by fluoroacetate Explain your reasoning. 

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