Differences in Energy Metabolism Between Trypanosomatidae

https://doi.org/10.1016/S0169-4758(98)01263-0Get rights and content

Abstract

Although various members of the family Trypanosomatidae generate energy in a similar way, fundamental differences also exist and are not always recognized. In this review, Louis Tielens and Jaap Van Hellemond discuss the known differences in carbohydrate metabolism among trypanosomatids, and especially compare Leishmania with trypanosomatids such as Trypanosoma brucei and Phytomonas spp. Special attention will be paid to differences in end-products of carbohydrate degradation, to differences in anaerobic capacities between the various trypanosomatids and to the components of their respiratory chains, including the presence or absence of a plant-like alternative oxidase. Furthermore, evidence will be discussed which indicates that the succinate produced by trypanosomatids is formed mainly via an oxidative pathway and not via reduction of fumarate, a process known to occur in parasitic helminths.

Section snippets

End-products of carbohydrate degradation

Trypanosomatidae degrade carbohydrates via glycolysis, and in all members of this family the first reactions of the classical Embden–Meyerhof pathway occur inside glycosomes, organelles unique to the order Kinetoplastida2, 3. Pyruvate, the end-product of glycolysis, is often degraded further in the single mitochondrion of these organisms. However, the participation of mitochondrial pathways in the degradation of carbohydrates varies widely, although all Trypanosomatidae contain a mitochondrion

Anaerobic capacity

During their life cycle, Trypanosomatidae encounter large variations in the availability of oxygen; for instance, bloodstream forms have ample oxygen available, whereas certain stages in the midgut of insects can be confronted with hypoxic conditions. Surprisingly, there are large differences in the anaerobic capacity of Trypanosomatidae. The long slender bloodstream form of T. brucei is in effect a facultative anaerobic organism and can function very adequately without oxygen[3], whereas

Electron-transport chains

There are essential differences in respiratory chains among Trypanosomatidae and between various developmental stages of at least some of them, but all species and stages have some kind of branched electron-transport chain, with terminal oxidases that all use oxygen as the final electron acceptor. In the first part of the electron-transport chain, electrons are donated to the ubiquinone/ubiquinol pool via various enzyme complexes, and in the second part of the chain, electrons are transferred

Succinate production by trypanosomatidae

In many Trypanosomatidae, succinate is an end-product of energy metabolism, albeit often a minor one. It has been suggested that this succinate is produced by fumarate reductase, an enzyme homologous to the Krebs cycle enzyme succinate dehydrogenase, which catalyses the reverse reaction—oxidation of succinate. Fumarate reductase is well-known in bacteria and parasitic helminths, where fumarate reduction functions as an electron sink in the anaerobic energy metabolism of these organisms40, 41, 42

Concluding remarks

The glycosomal part of energy metabolism is nearly identical in all Trypanosomatidae. However, long slender T. brucei show a slight deviation, as the sole end-product of the glycosome is 3-phosphoglycerate (3-PGA), and phosphoenolpyruvate (PEP) is converted to pyruvate in the cytosol and not to oxaloacetate in the glycosome.

The mitochondria of Trypanosomatidae, however, show a large variation in metabolic pathways, as some stages possess mitochondria that have the usual Krebs cycle activity and

Acknowledgements

We are grateful to Fred Opperdoes and Paul Michels for many stimulating discussions and for their very valuable comments on the manuscript. Research in the authors' laboratory was supported by The Netherlands Life Science Foundation (SLW) with financial aid from The Netherlands Organization for Scientific Research (NWO).

References (54)

  • F. Chaumont

    Aerobic and anaerobic glucose metabolism of Phytomonas sp. isolated from Euphorbia characias.

    Mol. Biochem. Parasitol.

    (1994)
  • M.P. Barrett

    The pentose phosphate pathway and parasitic protozoa.

    Parasitol. Today

    (1997)
  • J.J. Van Hellemond et al.

    Inhibition of the respiratory chain results in a reversible metabolic arrest in Leishmania promastigotes.

    Mol. Biochem. Parasitol.

    (1997)
  • D.T. Hart et al.

    The effects of carbon dioxide and oxygen upon the growth and in vitro transformation of Leishmania mexicana mexicana.

    Mol. Biochem. Parasitol.

    (1981)
  • A.O.M. Stoppani

    Effect of inhibitors of electron transport and oxidative phosphorylation on Trypanosoma cruzi respiration and growth.

    Mol. Biochem. Parasitol.

    (1980)
  • A.B. Clarkson

    Respiration of bloodstream forms of the parasite Trypanosoma brucei brucei is dependent on a plant-like alternative oxidase.

    J. Biol. Chem.

    (1989)
  • K. Stuart

    The RNA editing process in Trypanosoma brucei.

    Semin. Cell Biol.

    (1993)
  • D.S. Beattie et al.

    Oxidation of NADH by a rotenon and antimycin-sensitive pathway in the mitochondrion of procyclic Trypanosoma brucei brucei.

    Mol. Biochem. Parasitol.

    (1994)
  • G.W. Rogerson et al.

    Oxidative metabolism in mammalian and culture forms of Trypanosoma cruzi.

    Int. J. Biochem.

    (1979)
  • E. Martin et al.

    Identification of the terminal respiratory chain in kinetoplast mitochondrial complexes of Leishmania tropica promastigotes.

    J. Biol. Chem.

    (1979)
  • K. Kita

    Electron-transfer complexes of mitochondria in Ascaris suum.

    Parasitol. Today

    (1992)
  • A.G.M. Tielens

    Energy generation in parasitic helminths.

    Parasitol. Today

    (1994)
  • J.A. Urbina et al.

    Inhibition of phosphoenolpyruvate carboxykinase from Trypanosoma (Schizotrypanum) cruzi epimastigotes by 3-mercaptopicolinic acid: in vitro and in vivo studies.

    Arch. Biochem. Biophys.

    (1990)
  • J.J. Van Hellemond

    Rhodoquinone and complex II of the electron transport chain in anaerobically functioning eukaryotes.

    J. Biol. Chem.

    (1995)
  • K. Kita

    Electron-transfer complexes of Ascaris suum muscle mitochondria. III Composition and fumarate reductase activity of complex II.

    Biochim. Biophys. Acta

    (1988)
  • J.F. Turrens

    Inhibition of Trypanosoma cruzi and T. brucei NADH fumarate reductase by benzimidazole and anthelmintic imidazole derivatives.

    Mol. Biochem. Parasitol.

    (1996)
  • Opperdoes, F.R. (1995) in Biochemistry and Molecular Biology of Parasites (Marr, J.J. and Müller, M., eds), pp 19–32,...
  • Cited by (0)

    View full text