Metabolism parasitic protozoa

In many respects the basic features of amino acid and protein metabolism of parasitic protozoa and helminths resemble those of their mammalian hosts. Proteins can be broken down extracellularly or within lysosomes, and amino acids taken up and used for biosynthesis or energy metabolism. The pathways of amino acid metabolism are mostly the same as those used by animal cells. There are, nevertheless, some significant differences. Although no unique class of proteinase has been found in either protozoa or helminths, differences in specificity between parasite and host enzymes mean that inhibitors can be designed which selectively inactivate parasite enzymes. Because proteolysis is so important to many parasites at various stages of their life cycle, proteinase inhibitors are being studied and tested as potential antiparasitic agents... 

Lawrence, F. and Robert-Gero, M. (1991) S-Adenosylmethionine metabolism in parasitic protozoa. In Biochemical Protozoology (eds Coombs, G. H. and North, M. J.), Taylor and Francis, London, pp. 436-449. 

MANY, BUT NOT ALL, PARASITIC PROTOZOA COMPARTMENTALIZE PATHWAYS OF ENERGY METABOLISM WITHIN ORGANELLES... 

Since Leishmania can be cultured easily, this genus has served as an in vitro prototype for investigating drug resistance in parasitic protozoa. Two classes of drug-resistant Leishmania have been generated and characterized. The first is that in which a genetic lesion leads to impaired transport or metabolic function. Mutations in transport pathways (51) and in metabolic enzymes (52) have provided considerable insight into the avenues by which certain nutrients are metabolized in Leishmania. 

Leishmania, parasitic protozoa transmitted by flesh-eating flies, cause various diseases ranging from cutaneous or mucocutaneous lesions to splenic and hepatic enlargement with fever. Soilium stibogluconate (pentavalent antimony), the primary drug in all forms of the disease, appears to kill the parasite by inhibition of glycolysis or effects on nucleic acid metabolism. Alternative agents include pentamidine (for visceral leishmaniasis), metronidazole (for cutaneous lesions), and amphotericin B (for mucocutaneous leishmaniasis). 

Ullman B. Pyrazolopyrimidine metabolism in parasitic protozoa. Pharmaceutical Research 1984 l(5) 194-203. 

The most important biologically active 4,7-phenanthroline is 4,7-phenanthroline-5,6-dione (112), known as phanquone, Entobex, which is used medicinally as an amoebicide. It is active also against bacteria, protozoa, and other parasites.390 Several closely related derivatives are also highly active.224, 250, 251,258-261, 390,538,539 Phanquone is used particularly in treating amoebic dysentery and is often used in combination with other antibiotics.540-542 The effect of 4,7-phenanthroline-5,6-dione and its relatives on cell metabolism has been investigated.543 It has also been reported to be mutagenic.544... 

Purine and pyrimidine nucleotides are essential components of many biochemical molecules, from DNA and RNA to ATP and NAD. In recent years, the pyrimidine and especially the purine metabolism of parasitic helminths have been investigated extensively, mainly because they are different from the pathways in the mammalian host such that they have potential as targets for chemotherapeutic attack. For a review of purine and pyrimidine pathways in parasitic helminths and protozoa, see Berens et al. (1995). Although parasitic helminths do not synthesize purines de novo, but obtain them from the host, they do possess elaborate purine salvage pathways for a more economical management of this resource. Pyrimidines, on the other hand, are synthesized de novo by all parasitic flat-worms studied so far and, as with mammalian... 

Muller M (1980) The hydrogenosome. Symp Soc Gen Microbiol 30 127-142 Muller M (1985) Search for cell organelles in protozoa. J Protozool 32 559-563 Muller M (1992) Energy metabolism of ancestral eukaryotes a hypothesis based on the biochemistry of amitochondriate parasitic protists. BioSystems 28 33-40 Muller M (2003) Energy metabolism. Part I Anaerobic protozoa. In Marr J, Nilsen T, Komuniecki R (eds) Molecular medical parasitology. Academic, London, pp 125-139 Muller M, Hogg JF, de Duve C (1968) Distribution of tricarboxylic acid cyle enzymes andofgly-oxylate cycle enzymes between mitochondria and peroxisomes of Tetrahymena pyriformis. J Biol Chem 243 5385-5395... 

Paltauf F, Meingassner JG (1982) The absence of cardiolipin in hydrogenosomes of Trichomonas vaginalis and Tritrichomonas foetus. J Parasitol 68 949-950 Ryley JF (1955) Studies on the metabolism of the protozoa. 5. Metabolism of the parasitic flagellate Trichomonas foetus. Biochem J 59 361-369 Steinbiichel A, Muller M (1986) Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes. Mol Biochem Parasitol 20 57-65 Turner G, Muller M (1983) Failure to detect extranuclear DNA in Trichomonas vaginalis and Tritrichomonas foetus. J Parasitol 69 234-236... 

PolyP in protozoa was found long ago (Ebel et al., 1958b Mattenheimer, 1958 Janakidevi et al, 1965 Rosenberg, 1966). Its metabolism was studied with the purpose of searching for specific biochemical peculiarities of parasitic representatives of this taxon, which could offer prospects for drug development. 

Amino acids can be used as a source of energy by many parasites. In protozoa, in which amino acids may be the major and perhaps only energy source at certain stages of the life cycle, the picture of energy production derived from earlier studies which focused entirely on carbohydrate metabolism was often too simple. In parasitic helminths, amino acids probably play a lesser role in energy metabolism, and the general lack ol catabolism may relate to the heavy commitment to synthetic processes. 

With respect to amino acid metabolism some of the differences between host and parasite are somewhat subtle. Some parasite enzymes, for example, have properties which are clearly distinct from those of their mammalian counterparts, such as the cofactor dependence and regulation of glutamate dehydrogenases. The utilization of specific amino acids such as proline or the accumulation of others such as alanine reflects a difference in the relative importance of the pathways between parasite and host. Some differences are particularly striking, especially among anaerobic protozoa in... 

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