The regulation of phosphofructokinase in epimastigote Trypanosoma cruzi

AbstractGlycosomal (microbody)-enriched fractions prepared from epimastigote Trypanosoma cruzi were used as a partially purified source of phosphofructokinase. D-Fructose 6-phosphate showed sigmoidal kinetics at pH 7.0, but hyperbolic kinetics at pH 8.O. Various adenosine nucleotides were positive effectors; 5'-AMP was the most powerful. ATP showed hyperbolic kinetics under all conditions tested. Several described inhibitors and activators of mammalian phosphofructokinase were without significant effect on the trypanosomal enzyme; the absence of effect of D-fructose 2,6-bisphosphate is of particular note.PhosphofructokinaseD-Fructose 2,6-bisphosphate (Trypanosoma cruzi, Parasitic protozoan

The occurrence and distribution of α-hydroxy-acid dehydrogenase in some members of the order Kinetoplastida

AbstractLDH-X is the isoenzyme of lactate dehydrogenase found in mammalian spermatozoa, occurring in cytosolic and mitochondrial locations. Gossypol strongly inhibits it, and the spermicidal action of this compound is attributed to the disruption of a reducing shuttle. The flagellated protozoan, Trypanosoma cruzi, contains an enzyme activity similar to LDH-X, called α-hydroxy-acid dehydrogenase, which is here shown to possess cytosolic and glycosomal components. The glycosome is a microbody-like organelle containing the early glycolytic enzymes. We postulate that the inhibition of replication of T. cruzi by gossypol derives from interference with glycosomal reducing shuttles. T. lewisi resembles T. cruzi in this respect

Malaria: New Medicines for its Control and Eradication

Malaria is one of the most widespread infectious diseases of our time. About 40% of the world's population live in countries where the disease is endemic and around 243 million people suffer from the disease every year. The vast majority of the cases are in children under five, and often amongst the poorest populations. New generations of medicines will always be needed, since there is always the threat of resistance emerging. Recent years have seen a renaissance in the search for new antimalarials. Advances in genome-based target identification, and also in whole parasite screening technologies means that more tools are now available for drug discovery. Increased understanding of the importance of emerging markets and of corporate social responsibility means that the pharmaceutical industry is now heavily supporting malaria drug discovery projects. Financial support from governments and from private foundations is a key element here though: malaria drug discovery will never be self-sustaining. Recent years have seen a call for a new strategy to help drive the eradication of malaria. This will need new types of medicines, moving beyond simple control of the disease, to prevention of transmission and elimination of host reservoirs. Since these medicines will take over a decade to discover and develop, it is important to have a clear view on the ultimate target product profiles that we are searching to address. Success could see the relegation of malaria to text books of tropical medicine and parasitology.</jats:p

Pyrimidine metabolism in Trichomonas vaginalis

AbstractPyrimidine metabolism in Trichomonas vaginalis was investigated using washed cell suspensions of the organism with radiolabelled pyrimidine ring precursors and preformed pyrimidines. The precursors [14C]orotate, [14C]bicarbonate and [14C]aspartate were not incorporated into the pyrimidine bases of trichomonal nucleic acids, indicating that the protozoan is unable to synthesise the pyrimidine ring and is dependent on the salvage of exogenous pyrimidines. [3H]uracil, [3H]uridine, [3H]cytidine, deoxy[3H]cytidine and [3H]thymidine were all efficiently salvaged, and interconversion between cytosine and uracil nucleotides was detected. Thymidylate synthase activity was not detected, suggesting that T. vaginalis is dependent upon an exogenous supply of thymidine for TMP synthesis