Energy metabolism---glycolysis inhibition

Inhibitors of several enzymes in the glycolytic pathway, upon which survival of T. brucei is dependent, have been described. Lonidamine (29) has been shown to inhibit T. brucei hexokinase (IC50 = 850 pM) and be toxic to the parasite (T.b. LD50 = 50 pM) in culture [31]. A series of mannitol derivatives have been discovered, which inhibit T. brucei phos-phofructokinase (TbPFK) [32]. The most potent compound (30) within this series exhibits an IC50 = 23 pM in a recombinant enzyme assay and inhibits parasite growth in vitro (IC50 = 30 pM). 

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Altered glycolysis via inhibition of pyruvate kinase and other enzymes involved in brain energy metabolism [36]... 

The same intermediates of glycolysis and the citric acid cycle that activate isocitrate dehydrogenase are allosteric inhibitors of isocitrate lyase. When energy-yielding metabolism is sufficiently fast to keep the concentrations of glycolytic and citric acid cycle intermediates low, isocitrate dehydrogenase is inactivated, the inhibition of isocitrate lyase is relieved, and isocitrate flows into the glyoxylate pathway, to be used in the biosynthesis of carbohydrates, amino acids, and other cellular components. 

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