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Catabolism of deoxythymidylate in some trypanosomatids

Published online by Cambridge University Press:  06 April 2009

K. Al Chalabi  and
W. E. Gutteridge
K. Al Chalabi
Affiliation:
Biological Laboratory, University of Kent, Canterbury, Kent CT2 7NJ
W. E. Gutteridge
Affiliation:
Biological Laboratory, University of Kent, Canterbury, Kent CT2 7NJ
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Extract

An initial observation converning the failure of [3H]thymidine at high specific activity to be incorporated into the DNA of Crithidia fasciculata for more than a brief intitial period has been correlated with the presence at high specific activity in the organism of thymidine phosphorylase activity with an equilibrium in the direction of catabolism. This enzyme degrades thymidine to thymine which is not utilized by the organism. The enzyme has also been shown to be present in a number of other trypanosomatids, including the culture forms of Trypanosoma cruzi, where the specific activity was nearly as high as that in C. fasciculata.

Evidence is presented that in C. fasciculata, the culture forms of T. cruzi and possibly other species of trypanosomatid, the thymidine phosphorylase, together with a thymidylate phosphatase, forms a catabolic pathway which degrades thymine nucleotides to thymine, which is then excreated. About 60% of the thymine nucleotides made by organisms appear to be matabolized through the pathway, suggesting that their synthesis is not subject to completely effective regulatory control.

Type
Research Article
Information
Parasitology , Volume 74 , Issue 3 , June 1977 , pp. 299 - 312
Copyright
Copyright © Cambridge University Press 1977

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References

Al Chalabi, K. & Gutteridge, W. E. (1974). Thymine excretion in the Trypanosomatidae Journal of Protozoology 21, 449.Google Scholar
Andrews, P. (1965). The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochemical Journal 96, 595–606.CrossRefGoogle ScholarPubMed
Blank, J. G. & Hoffe, P. A. (1975). Purification and properties of thymidine phosphorylase from Salmonella typhimurium. Archives of Biochemistry and Biophysics 168, 259–65.CrossRefGoogle ScholarPubMed
Bodmer, W. F. & Grether, S. (1965). Uptake and incorporation of thymine, thymidine, uracil, uridine and 5-fluorouracil into the nucleic acids of Bacillus subtilis. Journal of Bacteriology 89, 1011–14.CrossRefGoogle ScholarPubMed
Burton, K. (1956). A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochemical Journal 62, 315–23.CrossRefGoogle ScholarPubMed
Chang, K. P., Chang, C. S. & Sassa, S. (1975). Heme biosynthesis in bacterium-protozoan symbioses: enzymic defects in host homoflagellates and complementary role of their intracellular symbiotes. Proceedings of the National Academy of Sciences USA 72, 2979–83.CrossRefGoogle Scholar
Cosgrove, W. B. & Skeen, M. J. (1970). The Cell cycle in Crithidia fasciculata. Temporal relationships between synthesis of deoxyribonucleic acid in the nucleus and kinetoplast. Journal of Protozoology 17, 172–7.CrossRefGoogle ScholarPubMed
Cross, G. A. M. & Manning, J. C. (1973). Cultivation of Trypanosoma brucei sspp. in semi-defined media. Parasitology 67, 315–31.CrossRefGoogle Scholar
Dewey, V. C & Kidder, G. W. (1973). Partial purification and properties of a nucleoside hydrolase form Crithidia. Archives of Biochemistry and Biophysics 157, 380–7.CrossRefGoogle Scholar
Friedkin, M. & Roberts, D. (1954 a). The enzymatic synthesis of nucleosides. I. Thymidine and phosphorylase in mammalian tissue. Journal of Biological Chemistry 207, 245–56.CrossRefGoogle ScholarPubMed
Friedkin, M. & Roberts, D. (1954 b). The enzymatic synthesis of nucleosides. II. Thymidine and related pyrimidine nucleosides. Journal of Biological Chemistry 207, 257–66.CrossRefGoogle ScholarPubMed
Fulton, J. D. & Spooner, D. F. (1959). Terminal respiration in certain mammalian trypanosomes. Experimental Parasitology 8, 137–62.CrossRefGoogle ScholarPubMed
Gaborak, Maria, Gutteridge, W. E. & Cover, B. (1973). Studies on the biochemistry of the blood and intracellular stages of Trypanosoma cruzi. Isolation of blood stages from infected rats. Journal of Protozoology 20, 525–6.Google Scholar
Gallo, R. C., Perry, S. & Breitman, T. R. (1967). The enzymatic mechanisms for deoxythymidine synthesis in human leukocytes I. Substrate inhibition by thymidine and activation by phosphate or arsenate. Journal of Biological Chemistry 242, 5059–68.CrossRefGoogle ScholarPubMed
Gutterrodge, W. E. (1976). Chemotherapy of Chagas's disease: the present position. Tropical Diseases Bulletin 73, 699–705.Google Scholar
Gutteridge, W. E. & Al, Chalabi K. (1973). Thymidine phosphorylase activity in Crithidia fasciculata. In Progress in Protozoology, Proceedings of the 4th International Congress of Protozoology (ed. de Puytorac, P. and Grain, J.), p. 164. Clermont-Ferrand: Universitë de Clermont.Google Scholar
Gutterodge, W. E., Cover, B. & Wharton, F. P. (1972). Studies on the biochemistry of the blood and intracellular stages of Trypanosoma cruzi. Isolation of intracellular stages from infected rats. Transactions of the Royal Society of Tropical Medicine and Hygiene 66, 355.CrossRefGoogle Scholar
Gutteridge, W. E., Gaborak, Maria & Cover, B. (1975). Further development of a method to isolate intracellular stages of Trypanosoma cruzi from infected rats. Transactions of the Royal Society of Tropical Medicine and Hygiene 69, 266.Google Scholar
Gutteridge, W. E., Knowler, J. & Coombes, J. D. (1969). Growth of Trypanosoma cruzi in human heart tissue cells and effects of aminonucleoside of puromycin, trypacidin and aminopterin. Journal of Protozoology 16, 521–5.CrossRefGoogle ScholarPubMed
Kidder, G. W. & Dutta, B. N. (1958). The growth and nutrition of Crithidia fasciculata. Journal of General Microbiology 18, 621–38.CrossRefGoogle ScholarPubMed
Lanham, S. M. (1968). Seperation of trypanosomes from the blood of infected rats and mice by anion-exchangers. Nature, London 218, 1273–4.CrossRefGoogle Scholar
Leloir, L. F. & Cardini, C. E. (1957). Characterization of phosphorus compounds by acid lability. Methods in Enzymology 3, 840–50.CrossRefGoogle Scholar
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265–75.CrossRefGoogle ScholarPubMed
Meyer, H. & De, Souza W. (1976). Electron microscopic study of Trypanosoma cruzi periplast in tissue cultures. I. Number and arrangement of the peripheral microtubules in the various forms of the parasite's life cycle. Journal of Protozoology 23, 385–90.CrossRefGoogle ScholarPubMed
Milton, J. D. & Cooper, E. H. (1964). Metabolism of thymidine and deoxycytidine 5' -mono-phosphate by leucocytes in vitro. Biochemical Journal 93, 14P.Google Scholar
Newton, B. A. (1956). A synthetic growth medium for the trypanosomatid flagellate, Strigomonas (Herpetomonas) oncopelti. Nature, London 177, 279–80.CrossRefGoogle Scholar
Newton, B. A. & Horne, R. W. (1957). Intracellular studies in Strigomonas oncopelti. I. Cytoplasmic structures containing ribonucleoprotein. Experimental Cell Research 13, 563–74.CrossRefGoogle Scholar
Rachmeler, M., Gerhart, J. & Rosner, J. (1961). Limited thymidine uptake in Escherichia coli due to an inducible thymidine phosphorylase. Biochimica et Biophysica Acta 99, 222–5.CrossRefGoogle Scholar
Razzell, W. E. & Casshyap, P. (1964). Substrate specificity and induction of thymidine phosphorylase in Escherichia coli. Journal of Biological Chemistry 239, 1789–93.CrossRefGoogle ScholarPubMed
Razzell, W. E. & Khorana, H. G. (1958). Purification and properties of a pyrimidine deoxyribose phosphorylase from Escherichia coli. Biochimica et Biophysica Acta 28, 562–6.CrossRefGoogle Scholar
Schwartz, M. (1971). Thymidine phosphorylase from Escherichia coli. Properties and kinetics. European Journal of Biochemistry 21, 191–8.CrossRefGoogle Scholar
Simpson, A. M. & Simpson, L. (1974). Labelling of Crithidia fasciculata DNA with [3H] thymidine. Journal of Protozoology 21, 379–82.CrossRefGoogle ScholarPubMed
Williamson, J. (1976). Chemotherapy of African trypanosomiasis. Tropical Diseases Bulletin 73, 531–42.Google ScholarPubMed
Williamson, J. & Cover, B. (1966). Seperation of blood cell-free trypanosomes and malaria parasites on a sucrose gradient. Transactions of the Royal Society of Tropical Medicine and Hygiene 60, 426–7.CrossRefGoogle Scholar