Abstract
Malaria is one of the world’s most devastating diseases, afflicting several hundred million people a year and killing an estimated two million of them, mostly children.1 The etiologic agent is a parasitic protozoan of the genus Plasmodium. The organism causes disease in its intraerythrocytic phase. A prominent feature of its development inside red blood cells is the degradation of hemoglobin. During its short cycle, the parasite consumes nearly all of the host hemoglobin, generating amino acids for its growth and maturation.2 This is a vast catabolic process since hemoglobin constitutes 95% of the soluble red blood cell protein. Degradation occurs in an acidic digestive vacuole and involves a series of proteases. Two aspartic proteases, termed plasmepsins,3′6 and one cysteine protease, called falcipain,4 have been purified from the digestive vacuole and characterized.5 The plasmepsins appear to make an initial attack on the native hemoglobin molecule, which is followed by proteolysis of the large fragments into small peptides by falcipain.5,7 Intact hemoglobin cannot be cleaved by falcipain unless the substrate is first denatured.8 Cysteine protease inhibitors cause osmotic swelling of the digestive vacuole and ultimately death of the parasite,4 perhaps through accumulation of plasmepsin digestion products that are too large to exit the vacuole.8 The products of digestive vacuole proteolysis are small peptides, which appear to be exported for terminal degradation by cytoplasmic expeptidases.
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Silva, A.M., Lee, A.Y., Erickson, J.W., Goldberg, D.E. (1998). Structural Analysis of Plasmepsin II. In: James, M.N.G. (eds) Aspartic Proteinases. Advances in Experimental Medicine and Biology, vol 436. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5373-1_51
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DOI: https://doi.org/10.1007/978-1-4615-5373-1_51
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