Fluoroacetate, prepared commercially for rodent control, is also produced by a S
ID: 1075752 • Letter: F
Question
Fluoroacetate, prepared commercially for rodent control, is also produced by a South African plant. After entering a cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase: F-CH,COO + CoA-SH + ATP F-CH,CO-S-CoA + AMP + PP. The toxic effect of fluoroacetate was studied in an experiment using intact isolated rat heart. After the hear 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 citric acid cycle intermediates revealed that their concentrations were below normal, except for citrate, with a concentratior 10 times higher than normal. What citric acid cycle enzyme is inhibited, and what is the inhibitor? O Aconitase is inhibited by fluoroacetate. O Isocitrate dehydrogenase is inhibited by fluorocitrate. O Citrate synthase is inhibited by fluorocitrate. O Citrate synthase is inhibited by fluoroacetate. O Aconitase is inhibited by fluorocitrate. O Isocitrate dehydrogenase is inhibited by fluoroacetate.Explanation / Answer
1. Fluoroacetate disrupts the citric acid cycle by combining with coenzyme A to form Fluoracetyl CoA, which reacts with oxaloacetate in the presence of citrate synthase to produce fluorocitrate. Fluorocitrate binds very tightly to Aconitase, to inhibit its action.
(5) Option is correct.
2. (6) Option is correct. Citrate, the first product of the citric acid cycle, can also inhibit PFK. If citrate builds up, this is a sign that glycolysis can slow down, because the citric acid cycle is backed up and doesn’t need more fuel.