Enzymes: 1, hexokinase; 2, phosphoglucose isomerase; 3, phosphofructokinase; 4, aldolase; 5, triosephosphate isomerase; 6, glyceraldehyde-3-phosphate dehydrogenase; 7, phosphoglycerate kinase; 8, glycerol-3-phosphate dehydrogenase; 9 glycerol kinase; 10, adenylate kinase; 11, glycerol-3-phosphate oxidase; 12, phosphoglycerate mutase; 13, enolase; 14, pyruvate kinase.
In the bloodstream stage of the African trypanosome, T. brucei , mitochondrial activity is completely suppressed and since these trypanosome have no energy stores they are totally dependent on glycolysis for a constant supply of energy. The first 7 enzymes of the Embden-Meyerhof Parnass pathway of glycolysis are sequestered inside glycosomes. Glucose has to cross two membrane sytems, the plasma membrane and the glycosomal membrane, before it can be phosphorylated by the glycosomal enzyme hexokinase. Under aerobic conditions 1 mole of glucose is converted to two moles of 3-phosphoglycerate, which is excreted into the cytosol, where it is converted to 2 moles of pyruvate with net synthesis of 2 moles of ATP per mole of glucose consumed. Reducing equivalents that are produced in the glyceraldehyde-3-phosphate dehydrogenase step are reoxidised by molecular oxygen via a cycle comprising a glycosomal glycerol-3-phosphate dehydrogenase (8) and a mitochondrial cyanide insensitive glycerol-3-phosphate oxidase (or Trypanosome Alternative Oxidase or TAO, 11). Under anaerobic conditions, or after inhibition of the oxidase by salicylhydroxamic acid, the latter cycle will be inoperative, leading to an accumulation of glycerol-3-phosphate inside the glycosome. This will enable the reversal of the glycerol kinase (9) reaction, the equilibrium of which is normally towards the formation of glycerol-3-phosphate and ADP. As a result 1 mole of glycerol and one mole of pyruvate per mole of glucose are consumed. Since under anaerobic conditions only one mole of pyruvate is produced per mole of glucose rather than two, half the amount of ATP is produced. This will slow down the motility of the trypanosomes. When the reversal of glycerol kinase is inhibited by mass action through an elevation the external glycerol concentration, anaerobic glycolysis comes to a stand still and trypanosomes will die.
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