Fluoroacetate is used as a poison for rat control. After entering a cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase: acetate thiokinase FCH₂COO- + COASH + ATP FCH₂CO-SCOA + AMP + PPi The toxic effect of fiuoroacetate was studied in an experiment using intact isolated rat heart. After the heart was perfused with 0.22 mM fluoroacetate, the measured rate of glucose uptake and glycolysis decreased, and glucose 6-phosphate and fructose 6-phosphate accumulated. Examination of citric acid cycle intermediates revealed that their concentration were below normal, except for citrate, with a concentration 10-fold higher than normal. (i) Where does the block in the citric acid cycle occur? What causes citrate to accumulate and the other cycle intermediates to be depleted? How might the inhibition be overcome? (ii). Fluoroacetyl-CoA is enzymatically transformed in the citric acid cycle. What is the structure of the end product of fluoroacetate metabolism? Why does it block the citric acid cycle?

Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
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Fluoroacetate is used as a poison for rat control. After entering a cell, fluoroacetate is
converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase:
acetate thiokinase
FCH₂COO-
+ COASH + ATP
FCH₂CO-SCOA
+ AMP
PP₁
The toxic effect of fiuoroacetate was studied in an experiment using intact isolated rat heart. After the
heart was perfused with 0.22 mM fluoroacetate, the measured rate of glucose uptake and glycolysis
decreased, and glucose 6-phosphate and fructose 6-phosphate accumulated. Examination of citric
acid cycle intermediates revealed that their concentration were below normal, except for citrate, with
a concentration 10-fold higher than normal.
(i) Where does the block in the citric acid cycle occur? What causes citrate to accumulate and
the other cycle intermediates to be depleted? How might the inhibition be overcome?
(ii). Fluoroacetyl-CoA is enzymatically transformed in the citric acid cycle. What is the structure
of the end product of fluoroacetate metabolism? Why does it block the citric acid cycle?
Transcribed Image Text:Fluoroacetate is used as a poison for rat control. After entering a cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase: acetate thiokinase FCH₂COO- + COASH + ATP FCH₂CO-SCOA + AMP PP₁ The toxic effect of fiuoroacetate was studied in an experiment using intact isolated rat heart. After the heart was perfused with 0.22 mM fluoroacetate, the measured rate of glucose uptake and glycolysis decreased, and glucose 6-phosphate and fructose 6-phosphate accumulated. Examination of citric acid cycle intermediates revealed that their concentration were below normal, except for citrate, with a concentration 10-fold higher than normal. (i) Where does the block in the citric acid cycle occur? What causes citrate to accumulate and the other cycle intermediates to be depleted? How might the inhibition be overcome? (ii). Fluoroacetyl-CoA is enzymatically transformed in the citric acid cycle. What is the structure of the end product of fluoroacetate metabolism? Why does it block the citric acid cycle?
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