Energy Metabolism and Carbon Flow in Cryptosporidium parvum
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Cryptosporidium lacks a Krebs cycle in the remnant mitochondria, thus probably solelyrelies on glycolysis to generate energy. The glycolytic pathway in this parasite consists ofenzymes with a complex evolutionary history and diverse phylogenetic affinities. A numberof enzymes are closely related to those of plants (e.g. PGluM, PGI, aldolase and GDH)or bacteria (e.g. PGM, MDH, LDH, ME, ADH1 and ADH-E). Some enzymes are characteristicto the microanaerobic lifestyle, such as PPi-PFK, which uses pyrophosphate ratherthan ATP. Glycolysis also provides precursors for at least two synthetic pathways: acetyl-CoA can be converted to malonyl-CoA for synthesizing fatty acid(s) and polyketide(s);and glycerol-3P may be used for synthesizing phospholipids. On the other hand, glycolysismay also produce three organic end-products (i.e. lactate, ethanol and acetate), whichis important for maintaining the carbon flow and recycling NAD(P)H. The glycolytic pathwaymay produce 3-5 net ATP molecules, which is much fewer than those generated bycomplete aerobic metabolism (up to 36 ATP). Some glycolytic enzymes are expressed atrelatively consistent levels during the parasite's life cycle (e.g. GAPDH and GPI), whileothers may be differentially expressed. For example, the expression of one of the two PPi-PFK orthologues is increased during the life cycle, while that of the other is decreased.The PGluM and LDH genes are expressed in free sporozoites at much higher levels thanat the intracellular stages, while ADH1 and ADH-E are expressed at much higher levels inthe late developmental stages. The preliminary biochemical features have been characterizedfor some enzymes using recombinant proteins, including LDH and MDH. Inhibitorstargeting this pathway are able to inhibit the parasite's growth, indicating that glycolyticand fermentative enzymes could be explored as drug targets against cryptosporidiosis. CAB International 2009.
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GIARDIA AND CRYPTOSPORIDIUM: FROM MOLECULES TO DISEASE