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Problem: Fluoroacetate, which is used for rodent control, is also produced by a South African plant. After entering a cell, fluoroacetate is converted to fluroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase:
F-CH2COO- + CoA-SH + ATP -> F-CH2CO-S-CoA + AMP + PPi
The toxic effects of fluroacetate was studied in an experiment using intact rat heart. After the heart was perfused with 0.20 mM fluoroacetate, the measured rate of glucose uptake and glycolysis decreased and Glu-6-P and Fruc-6-P accumulated. The TCA components revealed that they were below normal except for citrate which was 10 times higher than normal.
Required:
Question 1: Where did the block in the TCA cycle occur?
Question 2: In the heart perfusion, why did the glucose uptake and glycolysis decrease and why the phosphorylated hexoses accumulate?
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