[Frontiers in Bioscience 17, 349-374, January 1, 2012]

Multiple roles of proline transport and metabolism in trypanosomatids

Frederic Bringaud1, Michael P. Barrett2, Dan Zilberstein3

1Centre de Resonance Magnetique des Systemes Biologiques, UMR 5536, Universite Bordeaux Segalen, CNRS, Bordeaux, France, 2Wellcome Trust Centre for Molecular Parasitology, The College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom, 3Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Description of trypanosomatids
3.1. Trypanosoma brucei
3.2. Trypanosoma cruzi
3.3. Leishmania spp.
4. Proline transport and accumulation
4.1. Proline transport in Trypanosoma brucei
4.2. Proline transport in Trypanosoma cruzi
4.3. Proline transport in Leishmania spp.
4.4. Roles of proline transport in amino acid homeostasis and osmotic stress response
5. Proline metabolism
5.1. Introduction
5.2. Production of glutamate from proline
5.3. Proline degradation in the absence of glucose
5.3.1. Conversion of proline into alanine
5.3.2. Minor end products of proline metabolism
5.4. Proline metabolism in glucose-rich medium
5.5. Glucose metabolism
5.5.1. Production of succinate and acetate
5.5.2. Maintenance of glycosomal balances
5.5.3. Lactate production
5.6. Comparison of energy metabolism in glucose-rich and -depleted conditions
5.6.1. ATP production by oxidative phosphorylation versus substrate level phosphorylation
5.6.2. Respiratory chain activity is essential
5.6.3. Mitochondrial NADH dehydrogenase activities
5.6.4. Electron flow within the respiratory chain depends on glucose availability
5.7. Regulation of the metabolic switch
6. Proline racemases
7. Role for proline in trypanosomatid differentiation
8. Acknowledgements
9. References

1. ABSTRACT

Trypanosomatids are a large family of unicellular eukaryotes, many of which are parasites in higher eukaryotes including man. Much of our understanding of metabolism in these organisms has been gained form the study of the human infective representatives (Trypanosoma brucei subpecies, Trypanosoma cruzi and Leishmania spp.) which are transmitted by blood-feeding arthropods. The insect vectors of these parasites use proline as a principal carbon and energy source circulating in their haemolymph. Accordingly the insect-forms of the human infectious parasites have evolved to exploit abundant proline when in this environment, but being able to activate different biochemical pathways when in other environments. Interestingly, if glucose is available, metabolic capability can shift to make this carbohydrate the preferred substrate. Proline has also been shown to play key roles in osmoregulation, differentiation in representatives of the group and may even play a role in immunosuppression elicited by the American trypanosome T. cruzi. This review focuses on recent progress in understanding the different aspects of proline metabolism in trypanosomatids, with a particular interest on the insect forms.