(c) (1 ) Fluoroacetate, prepared commercially for rodent control, is also produced by a South Afri- can plant. After entering a cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase: F-CH2COO¯ + COA-SH + ATP F-CH2CO-SCOA + AMP + PPj The toxic effect of fluoroacetate 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 the cit- ric acid cycle intermediates revealed that their concentrations were below normal, except for citrate, with a concentration 10-fold higher than normal. Where did the block in the citric acid cycle occur? What caused citrate to accumulate and the other cycle intermediates to be depleted? Explain. Why does it block the citric acid cycle? Fluoroacetyl-CoA is enzymatically transformed in the citric acid cycle. Name and draw the structure of the end product of fluoroacetate metabolism? How might the inhibition be overcome? Explain.
(c) (1 ) Fluoroacetate, prepared commercially for rodent control, is also produced by a South Afri- can plant. After entering a cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase: F-CH2COO¯ + COA-SH + ATP F-CH2CO-SCOA + AMP + PPj The toxic effect of fluoroacetate 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 the cit- ric acid cycle intermediates revealed that their concentrations were below normal, except for citrate, with a concentration 10-fold higher than normal. Where did the block in the citric acid cycle occur? What caused citrate to accumulate and the other cycle intermediates to be depleted? Explain. Why does it block the citric acid cycle? Fluoroacetyl-CoA is enzymatically transformed in the citric acid cycle. Name and draw the structure of the end product of fluoroacetate metabolism? How might the inhibition be overcome? Explain.
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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