Fluoroacetate cellular effects

This type of effect can occur in all tissues and is caused by a metabolic inhibitor such as azide or cyanide, which inhibits the electron transport chain. Inhibition of one or more of the enzymes of the tricarboxylic acid cycle such as that caused by fluoroacetate (Fig. 6.7) also results in inhibition of cellular respiration (for more details of cyanide and fluoroacetate see chap. 7). 

Fluorocitrate is therefore a pseudosubstrate. As well as inhibiting cellular respiration, inhibition of the TCA cycle will also reduce the supply of 2-oxoglutarate. This may decrease the removal of ammonia via formation of glutamic acid and glutamine, and this might account for the convulsions seen in some species after exposure to fluoroacetate. The toxicity is manifested as a malfunction of the CNS and heart, giving rise to nausea, apprehension, convulsions, and defects of cardiac rhythm, leading to ventricular fibrillation. Fluoroacetate and fluorocitrate do not appear to inhibit other enzymes involved in intermediary metabolism, and the di- and trifluoroacetic acids are not similarly incorporated and therefore do not produce the same toxic effects. 

A. Fluoroacetate is metabolized to the toxic compound fluomcitiate, which blocks cellular metabolism by inhibiting the aconitase enzyme within the Krebs cycle. Clinical effects of poisoning are delayed (from 30 minutes to several hours) until fluoroacetate is metabolized to fluorocitiate. 

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