- # About the Author
- # About the web site
- # Our second web site
- # Question of the day
- A New Book of Biochemistry
- Acid Base Balance
- Animations Links
- Biochemical Techniques
- Biochemistry Quiz
- Biological Oxidation
- Chemistry of Carbohydrates
- Chemistry of Lipids and Eicosanoids
- Chemistry of Nucleotides
- Chemistry of Proteins
- Diabetes Mellitus
- Diet and Nutrition
- Facebook Group Posts
- Haem Synthesis and Degradation
- Hemoglobin and Hemoglobinopathies
- Liver Function Tests
- Metabolism – Carbohydrates
- Metabolism – Lipids
- Metabolism – Nucleotides
- Metabolism – Proteins
- Metabolism of Alcohol
- Molecular Biology
- Past Papers
- Power Point Presentations
- Practical Biochemistry
- Abnormal Urine
- Blood Glucose Estimation
- Blood Urea and Urea Clearance Estimation
- Normal Laboratory Reference Values
- Normal Urine Analysis
- Power point presentations
- Protein Precipitation Reactions
- Reactions of Carbohydrates
- Serum Creatinine and Creatinine clearance estimation
- Serum Total Protein estimation
- Practice Questions
- Quick revisions
- Renal Function Tests
- Semester Paper
- Students’ corner
- Water and Electrolyte balance and Imbalance
Mechanism of action of Fluoroacetate- “The rat poison”
B. TCA cycle
C. Fatty acid oxidation
D. Fatty acid synthesis
E. HMP pathway
The right answer is -B) TCA cycle.
Fluoroacetate is structurally similar to acetate, which has an important role in cellular metabolism.
Fluoroacetate disrupts the citric acid cycle (also known as the Krebs cycle or TCA cycle- Tricarboxylic acid cycle) by combining with coenzyme A to form Fluoroacetyl CoA, which reacts with oxaloacetate in the presence of citrate synthase (host enzyme) to produce fluorocitrate (Figure-1).
Figure-1- Activation of fluoroacetate is brought by Citrate synthase, an enzyme of TCA cycle
Fluorocitrate binds very tightly to Aconitase, to inhibit its action, (Figure-2) thereby inhibiting the citric acid cycle as a whole. This is an example of suicidal inhibition.
Figure-2- TCA cycle and the action of Aconitase
The direct effect of Fluoroacetate is on TCA cycle, but indirectly Glycolysis and other pathways are also inhibited.
Effect on Glycolysis
This inhibition results in an accumulation of citrate in the blood. Citrate and fluorocitrate are allosteric inhibitors of phosphofructokinase-1 (PFK-1), a key enzyme in the breakdown of Glucose. As PFK-1 is inhibited cells are no longer able to metabolize carbohydrates, depriving them of energy.
Effect on fatty acid oxidation
Inhibition of TCA cycle inhibits fatty acid oxidation also due to non availability of oxidized coenzymes, and incomplete utilization of Acetyl co A. But these are late implications. TCA cycle is vital to life. Death occurs immediately after its suppression. Directly Fluoroacetate has no effect on enzymes of fatty acid oxidation.
Similarly fatty acid synthesis and HMP pathway are not directly affected by Fluoroacetate.
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!