Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Apr 30;93(9):4126–4130. doi: 10.1073/pnas.93.9.4126

Aromatic amino acid transamination and methionine recycling in trypanosomatids.

B J Berger 1, W W Dai 1, H Wang 1, R E Stark 1, A Cerami 1
PMCID: PMC39498  PMID: 8633027

Abstract

Although trypanosomatids are known to rapidly transaminate exogenous aromatic amino acids in vitro and in vivo, the physiological significance of this reaction is not understood. In postmitochondrial supernatants prepared from Trypanosoma brucei brucei and Crithidia fasciculata, we have found that aromatic amino acids were the preferred amino donors for the transamination of alpha-ketomethiobutyrate to methionine. Intact C. fasciculata grown in the presence of [15N]tyrosine were found to contain detectable [15N]methionine, demonstrating that this reaction occurs in situ in viable cells. This process is the final step in the recycling of methionine from methylthioadenosine, a product of decarboxylated S-adenosylmethionine from the polyamine synthetic pathway. Mammalian liver, in contrast, preferentially used glutamine for this reaction and utilized a narrower range of amino donors than seen with the trypanosomatids. Studies with methylthioadenosine showed that this compound was readily converted to methionine, demonstrating a fully functional methionine-recycling pathway in trypanosomatids.

Full text

PDF
4126

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bacchi C. J., Sufrin J. R., Nathan H. C., Spiess A. J., Hannan T., Garofalo J., Alecia K., Katz L., Yarlett N. 5'-Alkyl-substituted analogs of 5'-methylthioadenosine as trypanocides. Antimicrob Agents Chemother. 1991 Jul;35(7):1315–1320. doi: 10.1128/aac.35.7.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Backlund P. S., Jr, Chang C. P., Smith R. A. Identification of 2-keto-4-methylthiobutyrate as an intermediate compound in methionine synthesis from 5'-methylthioadenosine. J Biol Chem. 1982 Apr 25;257(8):4196–4202. [PubMed] [Google Scholar]
  3. Backlund P. S., Jr, Smith R. A. Methionine synthesis from 5'-methylthioadenosine in rat liver. J Biol Chem. 1981 Feb 25;256(4):1533–1535. [PubMed] [Google Scholar]
  4. Bitonti A. J., Byers T. L., Bush T. L., Casara P. J., Bacchi C. J., Clarkson A. B., Jr, McCann P. P., Sjoerdsma A. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of S-adenosylmethionine decarboxylase. Antimicrob Agents Chemother. 1990 Aug;34(8):1485–1490. doi: 10.1128/aac.34.8.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CHATTERJEE A. N., GHOSH J. J. Transaminases of Leishmania donovani, the causative organism of kala-azar. Nature. 1957 Dec 21;180(4599):1425–1425. doi: 10.1038/1801425a0. [DOI] [PubMed] [Google Scholar]
  6. Constantsas N. S., Levis G. M., Vakirtzi-Lemonias C. S. Crithidia fasciculata tyrosine transaminase. I. Development, characterization and differentiation from alanine transaminase. Biochim Biophys Acta. 1971 Jan 26;230(1):137–145. [PubMed] [Google Scholar]
  7. Fairlamb A. H., Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol. 1992;46:695–729. doi: 10.1146/annurev.mi.46.100192.003403. [DOI] [PubMed] [Google Scholar]
  8. Ghoda L. Y., Savarese T. M., Northup C. H., Parks R. E., Jr, Garofalo J., Katz L., Ellenbogen B. B., Bacchi C. J. Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells. Mol Biochem Parasitol. 1988 Jan 15;27(2-3):109–118. doi: 10.1016/0166-6851(88)90030-8. [DOI] [PubMed] [Google Scholar]
  9. KIDDER G. W., DUTTA B. N. The growth and nutrition of Crithidia fasciculata. J Gen Microbiol. 1958 Jun;18(3):621–638. doi: 10.1099/00221287-18-3-621. [DOI] [PubMed] [Google Scholar]
  10. Koszalka G. W., Krenitsky T. A. 5'-Methylthioadenosine (MTA) phosphorylase from promastigotes of Leishmania donovani. Adv Exp Med Biol. 1986;195(Pt B):559–563. doi: 10.1007/978-1-4684-1248-2_87. [DOI] [PubMed] [Google Scholar]
  11. Langenbeck U., Möhring H. U., Dieckmann K. P. Gas chromatography of alpha-keto acids as their O-trimethyl silylquinoxalinol derivatives. J Chromatogr. 1975 Dec 10;115(1):65–70. doi: 10.1016/s0021-9673(00)89016-0. [DOI] [PubMed] [Google Scholar]
  12. Lanham S. M. Separation of trypanosomes from the blood of infected rats and mice by anion-exchangers. Nature. 1968 Jun 29;218(5148):1273–1274. doi: 10.1038/2181273a0. [DOI] [PubMed] [Google Scholar]
  13. Leelayoova S., Marbury D., Rainey P. M., Mackenzie N. E., Hall J. E. In vitro tryptophan catabolism by Leishmania donovani donovani promastigotes. J Protozool. 1992 Mar-Apr;39(2):350–358. doi: 10.1111/j.1550-7408.1992.tb01329.x. [DOI] [PubMed] [Google Scholar]
  14. Mackenzie N. E., Hall J. E., Flynn I. W., Scott A. I. 13C nuclear magnetic resonance studies of anaerobic glycolysis in Trypanosoma brucei spp. Biosci Rep. 1983 Feb;3(2):141–151. doi: 10.1007/BF01121945. [DOI] [PubMed] [Google Scholar]
  15. Miller R. L., Sabourin C. L., Krenitsky T. A. Trypanosoma cruzi adenine nucleoside phosphorylase. Purification and substrate specificity. Biochem Pharmacol. 1987 Feb 15;36(4):553–560. doi: 10.1016/0006-2952(87)90366-2. [DOI] [PubMed] [Google Scholar]
  16. Montemartini M., Santomé J. A., Cazzulo J. J., Nowicki C. Production of aromatic alpha-hydroxyacids by epimastigotes of Trypanosoma cruzi, and its possible role in NADH reoxidation. FEMS Microbiol Lett. 1994 May 1;118(1-2):89–92. doi: 10.1111/j.1574-6968.1994.tb06808.x. [DOI] [PubMed] [Google Scholar]
  17. Montemartini M., Santomé J. A., Cazzulo J. J., Nowicki C. Purification and partial structural and kinetic characterization of an aromatic L-alpha-hydroxy acid dehydrogenase from epimastigotes of Trypanosoma cruzi. Mol Biochem Parasitol. 1994 Nov;68(1):15–23. doi: 10.1016/0166-6851(94)00145-6. [DOI] [PubMed] [Google Scholar]
  18. Montemartini M., Santomé J. A., Cazzulo J. J., Nowicki C. Purification and partial structural and kinetic characterization of tyrosine aminotransferase from epimastigotes of Trypanosoma cruzi. Biochem J. 1993 Jun 15;292(Pt 3):901–906. doi: 10.1042/bj2920901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nowicki C., Montemartini M., Duschak V., Santomé J. A., Cazzulo J. J. Presence and subcellular localization of tyrosine aminotransferase and p-hydroxyphenyllactate dehydrogenase in epimastigotes of Trypanosoma cruzi. FEMS Microbiol Lett. 1992 Apr 15;71(2):119–124. doi: 10.1016/0378-1097(92)90498-d. [DOI] [PubMed] [Google Scholar]
  20. Rege A. A. Purification and characterization of a tyrosine aminotransferase from Crithidia fasciculata. Mol Biochem Parasitol. 1987 Aug;25(1):1–9. doi: 10.1016/0166-6851(87)90012-0. [DOI] [PubMed] [Google Scholar]
  21. Schlenk F., Zydek-Cwick C. R., Dainko J. L. 5'-Methylthioadenosine and related compounds as precursors of S-adenosylmethionine in yeast. Biochim Biophys Acta. 1973 Sep 14;320(2):357–362. doi: 10.1016/0304-4165(73)90316-4. [DOI] [PubMed] [Google Scholar]
  22. Seed J. R., Hall J. E., Price C. C. A physiological mechanism to explain pathogenesis in African trypanosomiasis. Contrib Microbiol Immunol. 1983;7:83–94. [PubMed] [Google Scholar]
  23. Stibbs H. H., Seed J. R. Chromatographic evidence for the synthesis of possible sleep-mediators in Trypanosoma brucei gambiense. Experientia. 1973 Dec;29(12):1563–1565. doi: 10.1007/BF01943919. [DOI] [PubMed] [Google Scholar]
  24. Sufrin J. R., Meshnick S. R., Spiess A. J., Garofalo-Hannan J., Pan X. Q., Bacchi C. J. Methionine recycling pathways and antimalarial drug design. Antimicrob Agents Chemother. 1995 Nov;39(11):2511–2515. doi: 10.1128/aac.39.11.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sugimoto Y., Fukui S. Studies on biological functions of 5'-methylthioadenosine vitamin B12-replacing effect for Ochromonas malhamensis. J Nutr Sci Vitaminol (Tokyo) 1976;22(2):89–100. doi: 10.3177/jnsv.22.89. [DOI] [PubMed] [Google Scholar]
  26. Tabor C. W., Tabor H. Polyamines. Annu Rev Biochem. 1984;53:749–790. doi: 10.1146/annurev.bi.53.070184.003533. [DOI] [PubMed] [Google Scholar]
  27. Wang S. Y., Adams D. O., Lieberman M. Recycling of 5'-methylthioadenosine-ribose carbon atoms into methionine in tomato tissue in relation to ethylene production. Plant Physiol. 1982 Jul;70(1):117–121. doi: 10.1104/pp.70.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yarlett N., Bacchi C. J. Effect of DL-alpha-difluoromethylornithine on methionine cycle intermediates in Trypanosoma brucei brucei. Mol Biochem Parasitol. 1988 Jan 1;27(1):1–10. doi: 10.1016/0166-6851(88)90019-9. [DOI] [PubMed] [Google Scholar]
  29. Yung K. H., Yang S. F., Schlenk F. Methionine synthesis from 3-methylthioribose in apple tissue. Biochem Biophys Res Commun. 1982 Jan 29;104(2):771–777. doi: 10.1016/0006-291x(82)90704-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES