The toxic agent in this plant has been identified as fluoroacetate or fluoroacet

Question

The toxic agent in this plant has been identified as fluoroacetate or fluoroacetic acid (FA) depending on pH. on the toxic nature of FA reveal that an FA is converted to fluoroacetyl-CoA and citrate accumulates. In vitro studies reveal that none of the enzymes of the citric acid cycle are inhibited by FA and fluoroacetyl-CoA is not an inhibitor of citrate synthase. Propose a reasonable explanation for the toxicity of fluoroacetate in animals that is consistent with the data. The amino acid glutamate is synthesized from alpha - ketoglutarate, a catalytic intermediate in the citric acid cycle. In order for glutamate to be synthesized without depleting citric acid cycle intermediates, more carbon must be added to the cycle to make excess alpha-ketoglutarate. a. Describe the net synthesis of alpha -ketoglutarate from methyl labelled pyruvate in which no citric acid cycle intermediates are depleted. You must show how pyruvate can be used as a starting material to synthesize two alpha-ketoglutarate molecules by introducing more carbons into the citric acid cycle than are lost (don't overlook CO_2). b Show the position(s) of the label from pyruvate in the alpha - ketoglutarate produced.

Explanation / Answer

1) In vivo, fluroacetate reacts with acetyl coA to form flurocitrate. This flurocitrate is a competitive inhibitor of the enzyme aconitase or citrate synthase. Aconitase is a stereo-specific enzyme that converts citrate to isocitrate. In vitro, aconitase does not get converted to flurocitrate and therefore aconitase is not blocked.

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