Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 160

Fluoroacetate combines with acetyl-CoA to form fluoroacetyl-CoA, which then combines with oxaloacetate to produce fluorocitrate. Fluorocitrate is converted to 4-hydroxy-trans-aconitate, which binds and inactivates aconitase resulting in inhibition of citrate oxidation. This results in inhibition of the tricarboxylic acid (TCA) or Kreb’s cycle, cellular energy depletion, citric acid and lactic acid accumulation, a decrease in blood pH, and interference with cellular respiration and metabolism of carbohydrates, lipids and proteins. Organs with cells with a high metabolic rate, such as the heart, brain and kidneys, are most susceptible to dysfunction (Goh et al., 2005; Parton, 2006; Proudfoot et al., 2006). In addition to blockade of the TCA cycle, citrate accumulates within blood to toxic concentrations and binds to calcium resulting in serum ionized hypocalcaemia.