Question

2. Some plants in Africa and Australia have been found to produce toxic fluorinated fatty acid derivatives such as o-Fluorooctadecanoic acid, as a defense mechanism against grazing by herbivores. Ingestion of these toxic compounds by livestock often results in fatal poisonings. The effects of o-Fluorooctadecanoic acid include: • decreased rate of glycolysis accumulation of fructose 6-phosphate decreased concentration of all citric acid cycle intermediates except for citrate, with the concentration 10 times greater than normal. • Based on these observations, determine: a. Why did glycolysis decrease? Why did fructose 6-phosphate accumulate? (7pt) b. What caused citrate to accumulate and other cycle intermediates to be depleted? (5pt) c. Why is poisoning with fluorinated fatty acid derivatives fatal? (5pt)

This is all the information given. This question was given on bio exam.

Answer 1

Glucose Fructose- phosphate a Inhibition (Allosteric) Рек Glycolysis ) Fructose !, 6-bisphosphate Pyruvate w-Fluordecanoil acid IC Onalo n acetate Fluor citrate water Malate Aconitase Citric Fumarate Acid Cycle succinate Cis-Acontate Inhibition 1 Aconitace k w ater Succinyl Troutrate LOAF & Katoglutaraty

F-he-cool I-U- C-Coo - 21 - J no-c-coot c- coo nc-coo Fluor Ser-o citrate Aconitase His iRn. -oocrc on No acontare binding F-c-coo " In-o-ser - ! ooc-c (coot U- flip step I - ooc - (- Cis-aconitate

Fig.1 Fig. 2.

1) Glycolysis is decreased due to accumulation of Fructose-6-Phosphate. The reason for the fructose-6-phosphate accumulation is the allosteric inhibition of enzyme Phosphofructokinase (PFK) by the fluorocitrate formation from precursor floroacetyl CoA  in the Citric acid Cycle (see Fig. 1).

2) The ω-fluoroocadecanoic acid by combining with acetyl CoA undergoes conversion to form fluoroacetyl CoA which further leads to the formation of fluorocitrate. The fluorocitrate is not capable of binding to aconitase (see Fig. 2) for its conversion to isocitrate which causes fluorocitrate accumulation and the halt of Citric Acid cycle and depletion of other Citric Acid cycle intermediates. Additionally, the fluorocitrate also acts as an allosteric inhibitor of Phosphofructokinase (PFK) that causes accumulation of fructose-6-phosphate and decreased glycolysis.

3)All the fluorinated derivatives of fatty acids are capable of undergoing conversion to fluoroacetyl CoA resulting in the halt of Citric Acid Cycle and deprived glycolysis thus preventing ATP production that is essential for the cellular respiration. Hence, fluorinated fatty acid derivative poisoning proves to be fatal.