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?
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
Section: Chapter Questions
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