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Novel biochemical pathways in parasitic protozoa

Published online by Cambridge University Press:  06 April 2009

A. H. Fairlamb
A. H. Fairlamb
Affiliation:
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT
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Summary

Throughout evolution, enzymes and their metabolites have been highly conserved. Parasites are no exception to this and differ most markedly by the absence of metabolic pathways that are present in the mammalian host. In general, parasites are metabolically lazy and rely on the metabolism of the host both for a supply of prefabricated components such as purines, fatty acids, sterols and amino acids and for the removal of end-products. Nonetheless, parasites are metabolically highly sophisticated in that (1) they retain the genetic capacity to induce many pathways, when needed, and (2) they have developed complex mechanisms for their survival in the host. Certain unique features of the metabolism of trypanosomes, leishmania, malaria and anaerobic protozoa will be discussed. This will include (1) glycolysis and electron transport with reference to the unique organelles: the glycosome and the hydrogenosome, (2) purine salvage, pyrimidine biosynthesis and folic acid metabolism and (3) polyamine and thiol metabolism with special reference to the role of the unique metabolite of trypanosomes and leishmanias, trypanothione.

Keywords

parasitic protozoachemotherapymetabolismglycolysiselectron transport
Type
Research Article
Information
Parasitology , Volume 99 , supplement S1: Symposium of the British Society for Parasitoiogy and the Linnean Society Special Issue: Research developments in the study of parasitic infections , January 1989 , pp. S93 - S112
Copyright
Copyright © Cambridge University Press 1989

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References

REFERENCES

Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. & Watson, J. D. (1983). Molecular Biology of the Cell. New York: Garland Publishing.Google Scholar
Aman, R. A., Kenyon, G. L. & Wang, C. C. (1985). Cross-linking of the enzymes in the glycosome of Trypanosoma brucei. Journal of Biological Chemistry 260, 6966–73.CrossRefGoogle ScholarPubMed
Aman, R. A. & Wang, C. C. (1986). Absence of substrate channeling in the glycosome of Trypanosoma brucei. Molecular and Biochemical Parasitology 19, 1–10.CrossRefGoogle ScholarPubMed
Aman, R. A. & Wang, C. C. (1987). Identification of two integral glycosomal membrane proteins in Trypanosoma brucei. Molecular and Biochemical Parasitology 25, 83–92.CrossRefGoogle ScholarPubMed
Bacchi, C. J. & McCann, P. P. (1987). Parasitic protozoa and polyamines. In Inhibition of Polyamine Metabolism (ed. McCann, P. P., Pegg, A. E. & Sjoerdsma, A.) pp. 317–344. New York: Academic Press.CrossRefGoogle Scholar
Bellofatto, V., Fairlamb, A. H., Henderson, G. B. & Cross, G. A. M. (1987). Biochemical changes associated with alpha-difluoromethylornithine uptake and resistance in Trypanosoma brucei. Molecular and Biochemical Parasitology 25, 227–38.CrossRefGoogle ScholarPubMed
Benchimol, M. & De Souza, W. (1983). Fine structure and cytochemistry of the hydrogenosome of Tritrichomonas foetus. Journal of Protozoology 30, 422–5.CrossRefGoogle ScholarPubMed
Benkovic, S. J., Fierke, C. A. & Naylor, A. M. (1988). Insights into enzyme function from studies on mutants of dihydrofolate reductase. Science 239, 1105–10.CrossRefGoogle ScholarPubMed
Beverley, S. M., Ellenberger, T. E. & Cordingley, J. S. (1986). Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major. Proceedings of the National Academy of Sciences, USA 83, 2584–8.CrossRefGoogle ScholarPubMed
Bitonti, A. J., Cross-Dorsen, E. & McCann, P. P. (1988). Effects of alpha-difluoromethylornithine on protein synthesis and synthesis of the variant-specific glycoprotein (VSG) in Trypanosoma brucei brucei. The Biochemical Journal 250, 295–8.CrossRefGoogle ScholarPubMed
Bowman, I. B. R., Grant, P. T. & Kermack, W. O. (1960). The metabolism of Plasmodium berghei, the malaria parasite of rodents. I. The preparation of the erythrocytic form of P. berghei separated from the host cell. Experimental Parasitology 9, 131–6.CrossRefGoogle Scholar
Braun-Breton, C., Jendoubi, M., Brunet, E., Perrin, L., Scaife, J. & Da Silva, P. L. (1986). In vivo time course of synthesis and processing of major schizont membrane polypeptides in Plasmodium falciparum. Molecular and Biochemical Parasitology 20, 33–43.CrossRefGoogle ScholarPubMed
Broman, K., Knupfer, A.-L., Ropars, M. & Deshusses, J. (1983). Occurrence and role of phosphoenolpyruvate carboxykinase in procyclic Trypanosoma brucei brucei glycosomes. Molecular and Biochemical Parasitology 8, 79–87.CrossRefGoogle ScholarPubMed
Bzik, D. J., Wu-Bo, L., Horii, T. & Inselburg, J. (1987). Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene. Proceedings of the National Academy of Sciences, USA 84, 8360–4.CrossRefGoogle ScholarPubMed
Carson, D. A. & Chang, K.-P. (1981). Phosphorylation and anti-Leishmanial activity of Formycin B. Biochemical and Biophysical Research Communications 100, 1377–83.CrossRefGoogle ScholarPubMed
Certa, U., Ghersa, P., Dobelli, H., Matile, H., Kocher, H. P., Shrivastava, I. K., Shaw, A. R. & Perrin, L. H. (1988). Aldolase activity of a Plasmodium falciparum protein with protective properties. Science 240, 1036–8.CrossRefGoogle ScholarPubMed
Chapman, A., Linstead, D. J., Lloyd, D. & Williams, J. (1985). 13C-NMR reveals glycerol as an unexpected major metabolite of the protozoan parasite Trichomonas vaginalis. FEBS Letters 191, 287–92.CrossRefGoogle ScholarPubMed
Chaput, M., Claes, V., Portelle, I. C., Cludts, I., Cravador, A., Burny, A., Gras, H. & Tartar, A. (1988). The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase. Nature, London 322, 454–5.CrossRefGoogle Scholar
Clarkson, A. B. Jr. & Brohn, F. H. (1976). Trypanosomiasis: an approach to chemotherapy by the inhibition of carbohydrate catabolism. Science 194, 204–6.CrossRefGoogle ScholarPubMed
Clayton, C. E. (1985). Structure and regulated expression of genes encoding fructose bisphosphate aldolase in Trypanosoma brucei. EMBO Journal 4, 2997–3003.CrossRefGoogle ScholarPubMed
Danson, M. J., Conroy, K., McQuattie, A. & Stevenson, K. J. (1987). Dihydrolipoamide dehydrogenase from Trypanosoma brucei. The Biochemical Journal 243, 661–5.CrossRefGoogle ScholarPubMed
Darling, T. N., Balber, A. E. & Blum, J. J. (1988). A comparative study of D-lactate, L-lactate and glycerol formation by four species of Leishmania and by Trypanosoma letvisi and Trypanosoma brucei gambiense. Molecular and Biochemical Parasitology 30, 253–8.CrossRefGoogle ScholarPubMed
Darling, T. N. & Blum, J. J. (1988). D-Lactate production by Leishmania braziliensis through the glyoxalase pathway. Molecular and Biochemical Parasitology 28, 121–8.CrossRefGoogle ScholarPubMed
Darling, T. N., Davis, D. G., London, R. E. & Blum, J. J. (1987). Products of Leishmania braziliensis glucose catabolism: Release of D-lactate and, under anaerobic conditions, glycerol. Proceedings of the National Academy of Sciences, USA 84, 7129–33.CrossRefGoogle ScholarPubMed
Dieckmann, A. & Jung, A. (1986). Mechanisms of sulfadoxine resistance in Plasmodium falciparum. Molecular and Biochemical Parasitology 19, 143–7.CrossRefGoogle ScholarPubMed
Docampo, R. & Moreno, S. N. J. (1984). Free-radical intermediates in the antiparasitic action of drugs and phagocytic cells. In Free Radicals in Biology, 6th Edn. (ed. Pryor, W. A.) pp. 243–288. New York: Academic Press.CrossRefGoogle Scholar
Docampo, R. & Moreno, S. N. J. (1986). Free radical metabolism of antiparasitic agents. Federation Proceedings 45, 2471–6.Google ScholarPubMed
Doolittle, R. F. (1988). More molecular opportunism. Nature, London 336, 18.CrossRefGoogle ScholarPubMed
Fahey, R. C. & Newton, G. L. (1983). Occurrence of low molecular weight thiols in biological systems. In Functions of Glutathione: Biochemical, Physiological, Toxicological and Clinical Aspects (ed. Larsson, A., Orrenius, S., Holmgren, A. & Mannervik, B.), PP. 251–260. New York: Raven Press.Google Scholar
Fahey, R. C., Newton, G. L., Arrick, B., Overdank-Bogart, T. & Aley, S. B. (1984). Entamoeba histolytica: a eukaryote without glutathione metabolism. Science 224, 70–2.CrossRefGoogle ScholarPubMed
Faik, P., Walker, J. I. H., Redmill, A. A. M. & Morgan, M. J. (1988). Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3′ sequences. Nature, London 332, 455–7.CrossRefGoogle ScholarPubMed
Fairlamb, A. H. (1981). Alternate metabolic pathways in protozoan energy metabolism. Parasitology 82, 1–30.Google Scholar
Fairlamb, A. H. (1988). Metabolism and functions of trypanothione with special reference to leishmaniasis. In Leishmaniasis: The Current Status and New Strategies for Control, vol. 163 (ed. Hart, D. T.) pp. 465–473. New York: Plenum Press/NATO ASI Series.Google Scholar
Fairĺamb, A. H., Blackburn, P., Ulrich, P., Chait, B. T. & Cerami, A. (1985). Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 227, 1485–7.CrossRefGoogle ScholarPubMed
Fairlamb, A. H. & Bowman, I. B. R. (1980). Uptake of the trypanocidal drug suramin by bloodstream forms of Trypanosoma brucei and its effect on respiration and growth rate in vivo. Molecular and Biochemical Parasitology 1, 315–33.CrossRefGoogle ScholarPubMed
Fairlamb, A. H. & Cerami, A. (1985). Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomatids. Molecular and Biochemical Parasitology 14, 187–98.CrossRefGoogle ScholarPubMed
Fairlamb, A. H. & Henderson, G. B. (1987). Metabolism of trypanothione and glutathionylspermidine in trypanosomatids. In Host—Parasite Cellular and Molecular Interactions in Protozoal Infections, vol. H11, (ed. Chang, K.-P. & Snary, D.) pp. 29–40. Berlin: Springer-Verlag/NATO ASI Series.CrossRefGoogle Scholar
Fairlamb, A. H., Henderson, G. B., Bacchi, C. J. & Cerami, A. (1987). In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei. Molecular and Biochemical Parasitology 24, 185–91.CrossRefGoogle ScholarPubMed
Fairlamb, A. H., Henderson, G. B. & Cerami, A. (1986). The biosynthesis of trypanothione and N1-glutathionylspermidine in Crithidia fasciculata. Molecular and Biochemical Parasitology 21, 247–57.CrossRefGoogle ScholarPubMed
Fairlamb, A. H., Henderson, G. B. & Cerami, A. (1989). Trypanothione is the primary target for arsenical drugs against African trypanosomes. Proceedings of the National Academy of Sciences, USA 86, 2607–11.CrossRefGoogle ScholarPubMed
Fairlamb, A. J., Oduro, K. K. & Bowman, I. B. R. (1979). Action of the trypanocidal drug suramin on the enzymes of aerobic glycolysis of Trypanosoma brucei in vivo. FEBS Special Meeting on Enzymes, Dubrovnik, Abstract S4–10.Google Scholar
Fairlamb, A. H. & Opperdoes, F. R. (1986). Carbohydrate metabolism in African trypanosomes, with special reference to the glycosome. In Carbohydrate Metabolism in Cultured Cells, (ed. Morgan, M. J.) pp. 183–224. New York: Plenum Publishing Corporation.CrossRefGoogle Scholar
Fairlamb, A. H., Opperdoes, F. R. & Borst, P. (1977). New approach to screening drugs for activity against African trypanosomes. Nature, London 265, 270–1.CrossRefGoogle ScholarPubMed
Ferone, R. (1977). Folate metabolism in malaria. Bulletin of the World Health Organization 55, 291–8.Google ScholarPubMed
Flynn, I. W. & Bowman, I. B. R. (1974). The action of trypanocidal arsenical drugs on Trypanosoma brucei and Trypanosoma rhodesiense. Comparative Biochemistry and Physiology 48B, 261–73.Google ScholarPubMed
Gardner, M. J., Bates, P. A., Ling, I. T., Moore, D. J., McCready, S., Gunas-Ekera, M. B. R., Wilson, R. J. M. & Williamson, D. H. (1988). Mitochondrial DNA of the human malarial parasite Plasmodium falciparum. Molecular and Biochemical Parasitology 31, 11–18.CrossRefGoogle ScholarPubMed
Garrett, C. E., Coderre, J. A., Meek, T. D., Garvey, E. P., Claman, D. M., Beverley, S. M. & Santi, D. V. (1984). A bifunctional thymidylate synthetase-dihydrofolate reductasse in protozoa. Molecular and Biochemical Parasitology 11, 257–65.CrossRefGoogle ScholarPubMed
Giffin, B. F., McCann, P. P., Bitonti, A. J. & Bacchi, C. J. (1986). Polyamine depletion following exposure to DL-alpha-difluoromethylornithine both in vivo and in vitro initiates morphological alterations and mitochondrial activation in a monomorphic strain of Trypanosoma brucei brucei. Journal of Protozoology 33, 238–43.CrossRefGoogle Scholar
Gilbert, R. J., Klein, R. A. & Miller, P. G. G. (1983). The role of threonine in the metabolism of acetyl coenzyme A by Trypanosoma brucei brucei. Comparative biochemistry and Physiology 74B, 277–81.Google Scholar
Gillin, F. D., Reiner, D. S. & McCann, P. P. (1984). Inhibition of growth of Giardia lamblia by difluoromethylornithine, a specific inhibitor of polyamine biosynthesis. Journal of Protozoology 31, 161–3.CrossRefGoogle ScholarPubMed
Grady, R. W., Beinen, E. J. & Clarkson, A. B. Jr. (1986 a). Esters of 3,4-di-hydroxybenzoic acid, highly effective inhibitors of the sn-glycerol-3-phosphate oxidase of Trypanosoma brucei brucei. Molecular and Biochemical Parasitology 21, 55–63.CrossRefGoogle Scholar
Grady, R. W., Bienen, E. J. & Clarkson, A. B. Jr. (1986 b). p-Alkyloxybenzhydroxamic acids, effective inhibitors of the trypanosome glycerol-3-phosphate oxidase. Molecular and Biochemical Parasitology 19, 231–40.CrossRefGoogle ScholarPubMed
Gruenberg, J., Schwendimann, B., Sharma, P. R. & Deshusses, J. (1980). Role of glycerol permeation in bloodstream form of Trypanosoma brucei. Journal of Parasitology 27, 484–91.Google ScholarPubMed
Grumont, R., Washtien, W. L., Caput, D. & Santi, D. V. (1986). Bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica: sequence homology with corresponding monofunctional proteins. Proceedings of the National Academy of Sciences, USA 83, 5387–91.CrossRefGoogle ScholarPubMed
Gutteridge, W. E., Dave, D. & Richards, W. H. G. (1979). Conversion of dihydroorotate to orotate in parasitic protozoa. Biochimica et Biophysica Acta 582, 390–401.CrossRefGoogle ScholarPubMed
Gutteridge, W. E. & Davies, M. J. (1982). Properties of the purine phosphoribosyltransferases of Trypanosoma cruzi. FEMS Microbiology Letters 13, 207–12.CrossRefGoogle Scholar
Gutteridge, W. E. & Rogerson, G. W. (1979). Biochemical aspects of the biology of Trypansoma cruzi. In Biology of the Kinetoplastida, vol. 2 (ed. Lumsden, W. H. R. & Evans, D. A.) pp. 619–652. New York: Academic Press.Google Scholar
Hammond, D. J., Aman, R. A. & Wang, C. C. (1985 a). The role of compartmentation and glycerol kinase in the synthesis of ATP within the glycosome of Trypanosoma brucei. Journal of Biological Chemistry 260, 15646–54.CrossRefGoogle ScholarPubMed
Hammond, D. J. & Bowman, I. B. R. (1980). Studies on glycerol kinase and its role in ATP synthesis in Trypanosoma brucei. Molecular and Biochemical Parasitology 2, 77–91.CrossRefGoogle ScholarPubMed
Hammond, D. J., Burchell, J. R. & Pudney, M. (1985 b). Inhibition of pyrimidine biosynthesis de novo in Plasmodium falciparum by 2-(4-t-butylcyclohexyl)-3-hydroxy-1,4-naphthoquinone in vitro. Molecular and Biochemical Parasitology 14, 97–109.CrossRefGoogle ScholarPubMed
Hammond, D. J. & Gutteridge, W. E. (1980). Enzymes of pyrimidine biosynthesis in Trypanosoma cruzi. Journal of Biological Chemistry 118, 259–62.Google ScholarPubMed
Hammond, D. J. & Gutteridge, W. E. (1982). UMP synthesis in the Kinetoplastida. Biochimica et Biophysica Acta 718, 1–10.CrossRefGoogle ScholarPubMed
Hammond, D. J. & Gutteridge, W. E. (1984). Purine and pyrimidine metabolism in the trypanosomatidae. Molecular and Biochemical Parasitology 13, 243–61.CrossRefGoogle ScholarPubMed
Hammond, D. J. & Gutteridge, W. E. (1983). Studies of the glycosomal orotate phosphoribosyl transferase of Trypanosoma cruzi. Molecular and Biochemical Parasitology 7, 319–30.CrossRefGoogle ScholarPubMed
Hammond, D. J., Gutteridge, W. E. & Opperdoes, F. R. (1981). A novel location for two enzymes of de novo pyrimidine biosynthesis in trypanosomes and Leishmania. FEBS Letters 128, 22–30.CrossRefGoogle ScholarPubMed
Hardy, L. W., Finer-Moore, J. S., Montfort, W. R., Jones, M. O., Santi, D. V. & Stroud, R. M. (1987). Atomic structure of thymidylate synthase: target for rational drug design. Science 235, 448–55.CrossRefGoogle ScholarPubMed
Hart, D. T., Baudhuin, P., Opperdoes, F. R. & De Duve, C. (1987). Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides. EMBO Journal 6, 1403–11.CrossRefGoogle ScholarPubMed
Hassan, H. F., Mottram, J. C. & Coombs, G. H. (1985). Subcellular localisation of purine-metabolising enzymes in Leishmania mexicana mexicana. Comparative Biochemistry and Physiology 81B, 1037–40.Google ScholarPubMed
Henderson, G. B., Fairlamb, A. H. & Cerami, A. (1987 a). Trypanothione dependent peroxide metabolism in Crithidia fasciculata and Trypanosoma brucei. Molecular and Biochemical Parasitology 24, 39–45.CrossRefGoogle ScholarPubMed
Henderson, G. B. & Fairlamb, A. H. (1987). Trypanothione metabolism: a chemotherapeutic target in trypanosomatids. Parasitology Today 3, 312–15.CrossRefGoogle ScholarPubMed
Henderson, G. B., Fairlamb, A. H., Ulrich, P. & Cerami, A. (1987 6). Substrate specificity of the flavoprotein trypanothione disulfide reductase from Crithidia fasciculata. Biochemistry 26, 3023–7.CrossRefGoogle ScholarPubMed
Henderson, G. B., Ulrich, P., Fairlamb, A. H., Rosenberg, I., Pereira, M., Sela, M. & Cerami, A. (1988). ‘Subversive’ substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas' disease. Proceedings of the National Academy of Sciences, USA 85, 5374–8.CrossRefGoogle ScholarPubMed
Heyworth, P. G., Gutteridge, W. E. & Ginger, C. D. (1982). Purine metabolism in Trichomonas vaginalis. FEBS Letters 141, 106–11.CrossRefGoogle ScholarPubMed
Honigberg, B. M., Volkman, D., Entzeroth, R. & Schloltyseck, E. (1984). A freeze-fracture electron microscope study of Trichomonas vaginalis Donne and Tritrichomonas foetus (Riedmuller). Journal of Protozoology 31, 116–31.CrossRefGoogle ScholarPubMed
Howard, R. F., Stanley, H. A., Campbell, G. H. & Reese, R. T. (1984). Proteins responsible for a punctate fluorescence pattern in Plasmodium Falciparum merozoites. American Journal of Tropical Medicine and Hygiene 33, 1055–9.CrossRefGoogle ScholarPubMed
Huber, M., Garfinkel, L., Gitler, C., Mirelman, D., Revel, M. & Rozenblatt, S. (1988). Nucleotide sequence analysis of an Entamoeba histolytica ferredoxin gene. Molecular and Biochemical Parasitology 31, 27–34.CrossRefGoogle ScholarPubMed
Hudson, A. T., Randall, A. W., Fry, M., Ginger, C. D., Hill, B., Latter, V. S., McHardy, N. & Williams, R. B. (1985). Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity. Parasitology 90, 45–55.CrossRefGoogle ScholarPubMed
Hutner, S. H. & Bacchi, C. J. (1979). Nutrition of the Kinetoplastida. In Biology of the Kinetoplastida, vol. 2 (ed. Lumsden, W. H. R. & Evans, D. A.) pp. 653–691. New York: Academic Press.Google Scholar
Jennings, F. W. (1988). Chemotherapy of trypanosomiasis: the potentiation of melarsoprol by concurrent difluoromethylornithine (DFMO) treatment. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 572–3.CrossRefGoogle ScholarPubMed
Keithly, J. S. & Fairlamb, A. H. (1988). Inhibition of Leishmania species by alpha-difluoromethylornithine. In Leishmaniasis: The Current Status and New Strategies for-Control, vol. 163 (ed. Hart, D. T.) pp. 729–737. New York: Plenum Press/NATO ASI Series.Google Scholar
Ketterer, B., Meyer, D. J., Coles, B. & Taylor, J. B. (1988). Glutathione transferases. In Liver Cells and Drugs (ed. Guillouzo, A.) pp. 67–79. Colloque INSERM/John Libbey Eurotext.Google Scholar
Kierszenbaum, F., Wirth, J. J., McCann, P. P. & Sjoerdsma, A. (1987). Arginine decarboxylase inhibitors reduce the capacity of Trypanosoma cruzi to infect and multiply in mammalian host cells. Proceedings of the National Academy of Sciences, USA 84, 4278–82.CrossRefGoogle ScholarPubMed
Kim, B. G., Sobota, A., Bitonti, A. J., McCann, P. P. & Byers, T. J. (1987). Polyamine metabolism in Acanthamoeba: polyamine content and synthesis of ornithine, putrescine, and diaminopropane. Journal of Protozoology 34, 278–84.CrossRefGoogle ScholarPubMed
King, A. & Melton, D. W. (1987). Characterisation of cDNA clones for hypoxanthine-guanine phosphoribyltransferase from the human malarial parasite, Plasmodium falciparum: comparisons to the mammalian gene and protein Nucleic Acids Research 15, 10469–81.CrossRefGoogle Scholar
Kleiner, D. E. & Johnston, M. (1985). Purification and properties of a secondary alcohol dehydrogenase from the parasitic protozoa Tritrichomonas foetus. Journal of Biological Chemistry 260, 8038–43.CrossRefGoogle Scholar
Krauth-Siegel, R. L., Enders, B., Henderson, G. B., Fairlamb, A. H. & Schirmer, R. H. (1987). Trypanothione reductase from Trypanosoma cruzi: purification and characterization of the crystalline enzyme. European Journal of Biochemistry 164, 123–128.CrossRefGoogle ScholarPubMed
Kruckeberg, W. C., Sander, B. J. & Sullivan, D. C. (1981). Plasmodium berghei: Glycolytic enzymes of the infected mouse erythrocyte. Experimental Parasitology 51, 438–43.CrossRefGoogle ScholarPubMed
Krungkrai, J., Webster, J. K. & Yuthavong, Y. (1989). De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. Molecular and Biochemical Parasitology 32, 25–38.CrossRefGoogle ScholarPubMed
Linstead, D. J. & Bradley, S. (1988). The purification and properties of two soluble reduced nicotinamide: acceptor oxidoreductases from Trichomonas vaginalis. Molecular and Biochemical Parasitology 27, 125–34.CrossRefGoogle ScholarPubMed
Linstead, D. & Cranshaw, M. A. (1983). The pathway of arginine catabolism in the parasitic flagellate Trichomonas vaginalis. Molecular and Biochemical Parasitology 8, 241–52.CrossRefGoogle ScholarPubMed
Lo, H.-S. & Chang, C.-J. (1982). Purification and properties of NADP-linked, alcohol dehydrogenase from Entamoeba histolytica. Journal of Parasitology 68, 372–7.CrossRefGoogle ScholarPubMed
Lo, H.-S. & Reeves, R. E. (1980). Purification and properties of NADPH: flavin oxidoreductase from Entamoeba histolytica. Molecular and Biochemical Parasitology 2, 23–30.CrossRefGoogle ScholarPubMed
Mack, S. R. & Muller, M. (1980). End products of carbohydrate metabolism in Trichomonas vaginalis. Comparative Biochemistry and Physiology 67B, 213–16.Google Scholar
Marchand, M., Poliszczak, A., Gibson, W. C., Wierenga, R. K., Opperdoes, F. R. & Michels, P. A. M. (1988). Characterization of the genes for fructose-bis-phosphate aldolase in Trypanosoma brucei. Molecular and Biochemical Parasitology 29, 65–76.CrossRefGoogle Scholar
Marr, J. J. (1980). Carbohydrate metabolism in Leishmania. In Biochemistry and Physiology of Protozoa, vol. 3, 2nd Edn. (ed. Levandowsky, M. & Hutner, S. H.) pp. 313–340. New York: Academic Press.Google Scholar
Marr, J. J. & Berens, R. L. (1982). Antileishmanial action of 4-thiopyrazolo(-3,4-d)pyrimidine and its ribonucleoside. Biochemical Pharmacology 2, 143–8.CrossRefGoogle Scholar
Marr, J. J. & Berens, R. L. (1983). Pyrazolopyrimidine metabolism in the pathogenic Trypanosomatidae. Molecular and Biochemical Parasitology 7, 339–56.CrossRefGoogle ScholarPubMed
Marr, J. J., Berens, R. L. & Nelson, D. J. (1978). Antitrypanosomal effect of allopurinol: Conversion in vivo to aminopyrazolopyrimidine nucleotides by Trypanosoma cruzi. Science 201, 1018–20.CrossRefGoogle Scholar
Marr, J. J. & Docampo, R. (1986). Chemotherapy for Chagas' disease: perspective of current therapy and considerations for future research. Reviews of Infectious Diseases 8, 884–903.CrossRefGoogle ScholarPubMed
McLaughlin, J. & Aley, S. (1985). The biochemistry and functional morpholoogy of the Entamoeba. Journal of Protozoology 32, 221–40.CrossRefGoogle ScholarPubMed
Meister, A. & Anderson, M. E. (1983). Glutathione. Annual Review of Biochemistry 52, 711–60.CrossRefGoogle ScholarPubMed
Michels, P. A. M., Poliszczak, A., Osinga, K. A., Misset, O., Van Beeuman, J., Wierenga, R. K., Borst, P. & Opperdoes, F. R. (1986). Two tandemly linked identical genes code for the glycosomal glyceraldehyde-phosphate dehydrogenase in Trypanosoma brucei. EMBO Journal 5, 1049–56.CrossRefGoogle ScholarPubMed
Milhous, W. K., Weatherly, N. F., Bowdre, J. H. & Desjardins, R. E. (1985). In vitro activities of an mechanisms of resistance to antifol antimalarial drugs. Antimicrobial Agents and Chemotherapy 27, 525–30.CrossRefGoogle ScholarPubMed
Miller, R. L. & Linstead, D. (1983). Purine and pyrimidine metabolizing activities in Trichomonas vaginalis extracts. Molecular and Biochemical Parasitology 7, 41–51.CrossRefGoogle ScholarPubMed
Misset, O. & Opperdoes, F. R. (1984). Simultaneous purification of hexokinase, class-1 fructose — bisphosphate aldolase, triosephosphate isomerase and phosphoglycerate kinase from Trypanosoma brucei. European Journal of Biochemistry 144, 475–83.CrossRefGoogle Scholar
Misset, O. & Opperdoes, F. R. (1987). The phosphoglycerate kinases from Trypanosoma brucei: a comparison of the glycosomal and the cytosolic isoenzymes and their sensitivity towards suramin. European Journal of Biochemistry 162, 493–500.CrossRefGoogle ScholarPubMed
Misset, O., Bos, O. J. M. & Opperdoes, F. R. (1986). Glycolytic enzymes of Trypanosoma brucei. Simultaneous purification, intraglycosomal concentrations and physical properties. European Journal of Biochemistry 157, 441–53.CrossRefGoogle ScholarPubMed
Mukkada, A. J. (1977). Tricarboxylic acid and glyoxylate cycles in the Leishmaniae. Acta Tropica 34, 167–75.Google ScholarPubMed
Muller, M. (1988). Energy metabolism of protozoa without mitochondria. Annual Review of Microbiology 42, 465–88.CrossRefGoogle ScholarPubMed
Nelson, D. J., Lafon, S. W., Tuttle, J. V., Miller, W. H., Miller, R. L., Krenitsky, T. A., Elion, G. B., Berens, R. L. & Marr, J. J. (1979). Allopurinol ribonucleoside as an antileishmanial agent. Journal of Biological Chemistry, 254, 11544–9.CrossRefGoogle ScholarPubMed
Oduro, K. K., Bowman, I. B. R., Flynn, I. W. (1980). Trypanosoma brucei: preparation and some properties of a multienzyme complex catalysing part of the glycolytic pathway. Experimental Parasitology 50, 240–50.CrossRefGoogle ScholarPubMed
Opperdoes, F. R. (1982). The glycosome. Annals of the New York Academy of Sciences 386, 543–5.CrossRefGoogle Scholar
Opperdoes, F. R. (1987). Compartmerttation of carbohydrate metabolism in trypanosomes. Annual Review of Microbiology 41, 127–51.CrossRefGoogle ScholarPubMed
Opperdoes, F. R. (1988). Glycosomes may provide clues to the import of peroxisomal proteins. Trends in Biochemical Sciences 13, 255–60.CrossRefGoogle Scholar
Opperdoes, F. R., Baudhuin, P., Coppens, I., De Roe, C., Edwards, S. W., Weijers, P. J. & Misset, O. (1984). Purification, morphometric analysis, and characterization of the glycosomes (microbodies) of the protozoan hemoflagellate Trypanosoma brucei. Journal of Cell Biology 98, 1178–84.CrossRefGoogle ScholarPubMed
Opperdoes, F. R. & Borst, P. (1977). Localization of nine glycolytic enzymes in a microbody-like organelle in Trypanosoma brucei: the glycosome. FEBS Letters 80, 360–4.CrossRefGoogle Scholar
Opperdoes, F. R., Borst, P. & Fonck, K. (1976). The potential use of inhibitors of glycerol-3-phosphate oxidase for chemotherapy of African trypanosomiasis. FEBS Letters 62, 169–72.CrossRefGoogle ScholarPubMed
Osinga, K. A., Swinkels, B. W., Gibson, W. C., Borst, P., Veeneman, G. H., Van Boom, J. H., Michels, P. A. & Opperdoes, F. R. (1985). Topogenesis of microbody enzymes: a sequence comparison of the genes for the glycosomal (microbody) and cytosolic phosphoglycerate kinases of Trypanosoma brucei. EMBO Journal 4, 3811–17.CrossRefGoogle ScholarPubMed
Pascal, R. A., Le Trang, N., Cerami, A. & Walsh, C. (1983). Purification and properties of dihydroorotate oxidase from Crithidia fasciculata and Trypanosoma brucei. Biochemistry 22, 171–8.CrossRefGoogle ScholarPubMed
Pegg, A. E. & McCann, P. P. (1988). Polyamine metabolism and function in mammalian cells and protozoans. ISI Atlas of Science: Biochemistry, 11–18.Google Scholar
Peixoto, M. P. & Beverley, S. M. (1987). In vitro activity of sulfonamides and sulfones against Leishmania major promastigotes. Antimicrobial Agents and Chemotherapy 31, 1575–8.CrossRefGoogle ScholarPubMed
Penketh, P. G., Kennedy, W. P. K., Patton, C. L. & Sartorelli, A. C. (1987). Trypanosomatid hydrogen peroxidase metabolism. FEBS Letters 221, 427–31.CrossRefGoogle Scholar
Perrin, L. H., Merkli, B., Gabra, M. S., Stocker, J. W., Chizzolini, C. & Richie, R. (1985). Immunization with a Plasmodium falciparum merozoite surface antigen induces a partial immunity in monkeys. Journal of Clinical Investigation 75, 1718–21.CrossRefGoogle ScholarPubMed
Peters, W. (1987). Chemotherapy and Drug Resistance in Malaria. 2nd Edn.London: Academic Press.Google Scholar
Phillips, M. A., Coffino, P. & Wang, C. C. (1987). Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei: implications for enzyme turnover and selective difluoromethylornithine inhibition. Journal of Biological Chemistry 262, 8721–7.CrossRefGoogle ScholarPubMed
Poulin, R., Larochelle, J. & Nadeau, P. (1984). Polyamines in Acanthamoeba castellanii: presence of an unusually high, osmotically sensitive pool of 1,3-diaminopropane. Biochemical and Biophysical Research Communications 122, 388–93.CrossRefGoogle ScholarPubMed
Queen, S. A., Jagt, D. A. & Reyes, P. (1988). Properties of substrate specificity of a purine phosphoribosyltransferase from the human malaria parasite, Plasmodium falciparum. Molecular and Biochemical Parasitology 30, 123–34.CrossRefGoogle ScholarPubMed
Rainey, P. & Santi, D. V. (1983). Metabolism and mechanism of action of formycin B in Leishmania. Proceedings of the National Academy of Sciences, USA 80, 288–92.CrossRefGoogle ScholarPubMed
Reeves, R. E. (1984). Metabolism of Entamoeba histolytica Schaudinn, 1903. Advances in Parasitology 23, 105–42.CrossRefGoogle ScholarPubMed
Reeves, R. E., Guthrie, J. D. & Lobelle-Rich, P. (1980). Entamoeba histolytica: isolation of ferredoxin. Experimental Parasitology 49, 83–8.CrossRefGoogle ScholarPubMed
Reyes, P., Rathod, P. K., Sanchez, D. J., Mrema, J. E. K., Rieckmann, K. H. & Heidrich, H.-G. (1982). Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. Molecular and Biochemical Parasitology 5, 275–90.CrossRefGoogle ScholarPubMed
Rogers, S., Wells, R. & Rechsteiner, M. (1986). Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 234, 364–8.CrossRefGoogle ScholarPubMed
Roth, E. F. Jr., Calvin, M.-C., Max-Audit, I., Rosa, J. & Rosa, R. (1988). The enzymes of the glycolytic pathway in erthrocytes infected with Plasmodium falciparum malaria parasites. Blood 72, 1922–5.CrossRefGoogle Scholar
Sander, B. J. & Kruckeberg, W. C. (1981). Plasmodium berghei: glycolytic intermediate concentrations of the infected mouse erthrocyte. Experimantal Parasitology 52, 1–8.CrossRefGoogle Scholar
Shames, S. L., Fairlamb, A. H., Cerami, A. & Walsh, C. T. (1986). Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulphide-containing flavoprotein reductases. Biochemistry 25, 3519–26.CrossRefGoogle Scholar
Shames, S. L., Kimmel, B. E., Peoples, O. P., Agabian, N. & Walsh, C. T. (1988). Trypanothione reductase of Trypanosoma congolense: gene isolation primary sequence determination, and comparison to glutathione reductase. Biochemistry 27, 5014–19.CrossRefGoogle ScholarPubMed
Sherman, I. W. (1979). Biochemistry of Plasmodium (malarial parasites). Microbiological Reviews 43, 453–95.CrossRefGoogle ScholarPubMed
Shim, H. & Fairlamb, A. H. (1988). Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata. Journal of General Microbiology 134, 807–17.Google ScholarPubMed
Slocum, R. D., Bitonti, A. J., McCann, P. P. & Feirer, R. P. (1988). DL-alpha-difluoromethyl[3,4-3H]arginine metabolism in tobacco and mammalian cells. The Biochemical Journal 255, 197–202.CrossRefGoogle Scholar
Smith, D. B., Davern, K. M., Board, P. G., Tiu, W. U., Garcia, E. G. & Mitchell, G. F. (1986). Mr 26000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase. Proceedings of the National Academy of Sciences, USA 83, 8703–7.CrossRefGoogle Scholar
Steinbuchel, A. & Muller, M. (1986 a). Glycerol, a metabolic end product of Trichomonas vaginalis and Trichomonas foetus. Molecular and Biochemical Parasitology 20, 45–55.CrossRefGoogle Scholar
Steinbuchel, A. & Muller, M. (1986 b). Anaerobic pyruvate metabolism of Trichomonas foetus and Trichomonas vaginalis hydrogenosomes. Molecular and Biochemical Parasitology 20, 57–65.CrossRefGoogle ScholarPubMed
Stokstad, E. L. R. & Koch, J. (1967). Folic acid metabolism. Physiological Reviews 47, 83–116.CrossRefGoogle ScholarPubMed
Swinkels, B. W., Evers, R. & Borst, P. (1988). The topogenic signal of the glycosomal (microbody) phosphoglycerate kinase of Crithidia fasciculata residues in a carboxy-terminal extension. EMBO Journal 7, 1159–65.CrossRefGoogle Scholar
Swinkels, B. W., Gibson, W. C., Osinga, K. A., Kramer, R., Veeneman, G. H., Van Boom, J. H. & Borst, P. (1986). Characterization of the gene for the microbody (glycosomal) triosephosphate isomerase of Trypanosoma brucei. EMBO Journal 5, 1291–8.CrossRefGoogle ScholarPubMed
Tabor, C. W. & Tabor, H. (1984). Polyamines. Annual Review of Biochemistry 53, 749–90.CrossRefGoogle ScholarPubMed
Taylor, J. B., Vidal, A., Torpier, G., Meyer, D. J., Roitsch, C., Bolloul, J., Southan, C., Sondermeyer, P., Pemble, S., Lecocq, J., Capron, A. & Ketterer, B. (1988). The glutathione transferase activity and tissue distribution of a cloned M 28 K protective antigen of Schistosoma mansoni. EMBO Journal 7, 465–72.CrossRefGoogle Scholar
Tuttle, J. V. & Krenitsky, A. J. (1980). Purine phosphoribosyltransferases from Leishmania donovani. Journal of Biological Chemistry 255, 909–16.CrossRefGoogle ScholarPubMed
Van Schaftingen, E., Opperdoes, F. R. & Hers, H.-G. (1985). Stimulation of Trypanosoma brucei pyruvate kinase by fructose 2,6-bisphosphate. European Journal of Biochemistry 153, 403–6.CrossRefGoogle ScholarPubMed
Van Schaftingen, E., Opperdoes, F. R. & Hers, H. (1987). Effects of various metabolic conditions and of the trivalent arsenical melarsen oxide on the intracellular levels of fructose 2,6-bisphosphate and of glycolytic intermediates in Trypanosoma brucei. European Journal of Biochemistry 166, 653–61.CrossRefGoogle ScholarPubMed
Visser, N., Opperdoes, F. R. & Borst, P. (1981). Subcellular compartmentation of glycolytic intermediates in Trypanosoma brucei. European Journal of Biochemistry 118, 521–6.CrossRefGoogle ScholarPubMed
von Brand, T. (1973). Biochemistry of Parasites, 2nd Edn.New York: Academic Press.Google Scholar
Wang, C. C. (1983). Parasite enzymes as potential targets for antiparasitic chemotherapy. Journal of Medicinal Chemistry 27, 1–9.CrossRefGoogle Scholar
Wang, C. C., Verham, R., Tzeng, S.-F., Aldritt, S. & Cheng, H.-W. (1983). Pyrimidine metabolism in Tritrichomonas foetus. Proceedings of the National Academy of Sciences, USA 80, 2564–8.CrossRefGoogle ScholarPubMed
Webster, H. K. & Whaun, J. M. (1981). Purine metabolism during continuous erythrocyte culture of human malaria parasites (Plasmodium falciparum). Progress in Clinical and Biological Research 55, 557–70.Google Scholar
Weinbach, E. C. & Diamond, L. S. (1974). Entamoeba histolytica: 1. Aerobic metabolism. Experimental Parasitology 35, 232–43.CrossRefGoogle Scholar
Who Scientific Group (1987). The biology of malaria parasites WHO Technical Report Series No. 743. Geneva: World Health Organization.Google Scholar
Wierenga, R. K., Swinkels, B. W., Michels, P. A. M., Osinga, K., Misset, O., Van Beeumen, J., Gibson, W. C., Postma, J. P. M., Borst, P., Opperdoes, F. R. & Hol, W. G. J. (1987). Common elements on the surface of glycolytic enzymes from Trypanosoma brucei may serve as topogenic signals for import into glycosomes. EMBO Journal 6, 215–21.CrossRefGoogle ScholarPubMed
Yarlett, N. & Bacchi, C. J. (1980). Effect of DL-alpha-difluoromethylornithine on polyamine synthesis and interconversion in Trichomonas vaginalis grown in a semi-defined medium. Molecular and Biochemical Parasitology 31, 1–10.CrossRefGoogle Scholar
Ziegler, D. M. (1985). Role of reversible oxidation-reduction in enzyme thiols-disulfides in metabolic regulation. Annual Review of Microbiology 54, 305–29.Google ScholarPubMed