This question is related to the Citric Acid Cycle in the Cel

1. When a culture of rat cardiac tissue was exposed to the rodenticide fluoroacetate the cells demonstrated several metabolic abnormalities including but not limited to: 1. Increased steady-state concentrations of glucose-6-phosphate and fructose-6-phosphate. 2. Below normal concentrations for all citric acid cycle intermediates except for citrate whose concentration was 10 times higher than normal. Studies have indicated that upon cellular entry fluoroacetate is enzymatically modified to fluoroacetyl-CoA by the enzyme thiokinase. Given this data answer the following questions: a. What is the end product of fluoroacetate within the cell (1 point)? b. Explain how this product (from a.) accounts for the increases in glucose-6- phosphate, fructose-6-phosphate, and citrate (4 points).

Solution

a. What is the end product of fluoroacetate within the cell(1 point)?

citrate.

After entering the cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase:

Fluorocitrate is the product, it competes with citrate for the active site of aconitase a,

its structure suggests it is probably a competetive inhibitor.

It\'s effect can therefore be overcome by excess citrate.

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Explain how this product (from a.) accounts for the increases in glucose-6-phosphate, fructose-6-phosphate, and citrate

Since citrate is an inhibitor of phosphofructokinase 1, and glycolytic intermediates upstream of phosphofructokinase 1 are elevated,

it is likely that fluorocitrate inhibits phosphofructokinase 1.