Trypanosoma brucei pyruvate kinase (TbPYK)

Trypanosoma brucei pyruvate kinase (TbPYK) is a critical enzyme in the glycolytic pathway of the protozoan parasite responsible for African Sleeping Sickness (UniProt: P22141). In the bloodstream form of the parasite, TbPYK catalyzes the final, irreversible step of glycolysis, which serves as the sole source of ATP production due to the lack of a functional tricarboxylic acid cycle and oxidative phosphorylation (PubMed: 11092888). Unlike its human counterparts, TbPYK is uniquely regulated by fructose-2,6-bisphosphate rather than fructose-1,6-bisphosphate, providing a distinct structural site for selective drug targeting (PubMed: 10747965). Inhibition of this enzyme leads to rapid metabolic collapse and parasite death, making it a highly validated target for the development of new anti-trypanosomal therapies (PubMed: 22403116). Current research focuses on identifying small-molecule allosteric inhibitors that exploit the unique regulatory mechanisms of the parasite enzyme to ensure high selectivity and minimal host toxicity (PubMed: 25658147).

Other names

Pyruvate kinaseATP:pyruvate 2-O-phosphotransferaseTbPKPK

Inhibition of the final step of glycolysis, preventing the conversion of phosphoenolpyruvate to pyruvate and resulting in the depletion of cellular ATP within the parasite (PubMed: 21834571).