Fluoroacetate

Metabolism of fluoroacetate produces an inhibitor of the citric acid cycle enzyme, aconitase. Fluoroacetate is known as a suicide substrate because by itself it is not toxic to cells, but it kills cells by being made into a toxic substance. For fluoroacetate, this occurs as follows:

Cells readily convert fluoroacetate to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase (reaction diagram). Fluoroacetyl-CoA can combine with oxaloacetate to form fluorocitrate in a reaction catalyzed by the citric acid cycle enzyme, citrate synthase. Fluorocitrate is toxic to cells because it inhibits aconitase.

Fluoroacetate is a plant product that has been used as a pesticide. Its use by ranchers in the West to control coyote populations has led also to the death of eagles.

See also: Fluorocitrate, Acetate Thiokinase, Aconitase, Citrate Synthase