Macheton

Reviews

Metabolic Aspects of Glycosomes in Trypanosomatidae – New Data and Views
P.A.M. Michels, V. Hannaert and F. Bringaud
The energy metabolism of Trypanosomatidae has been the subject of many reviews during the past decade. In recent years, however, new data have led to a more complete picture of trypanosomatid metabolism and a reappraisal of the role of some characteristic organelles inthe energy supply of these parasites. For years, the glycosome was thought to be a peroxisome-like organelle that had evolved to allow the parasites to carry out glycolysis at a high rate using a relatively small amount of enzyme. However, the results of recent studies of trypanosomatid glycolysis and the detection of various other pathways and enzymes in the organelle necessitate a modificationof this view. Here, Paul Michels, Véronique Hannaert and Frédéric Bringaud review the new data and discuss the possible implications for our view on the role of the glycosome *. Carbohydrate metabolism in Trypanosomatidae is compartmentalized in a unique way, and the notion that this compartmentation must be important for the energy supply of these parasitic protozoa is widely accepted1–4.However, the results of recent research indicate that some aspects of regularly advocated ideas about the role of this compartmentation might be incorrect and/or incomplete. The role of the glycosome in energy and carbohydrate metabolism In all trypanosomatids, most glycolytic enzymes are found in specific organelles – the glycosomes5. Glycosomes also contain typical peroxisomal enzyme systems and theirroute of biogenesis is similar and homologous to that of peroxisomes in other organisms6,7. Glycosomes and glycolysis have been particularly well studied in the bloodstream form of Trypanosoma brucei, which, for several reasons, constitutes an excellent model for such analyses. First, this adaptative form is entirely dependent on glycolysis for its supply of ATP, with glucose as the preferredenergy source, and fructose, mannose and glycerol as alternative substrates. Various other trypanosomatids prefer amino acids or fatty acids as energy substrates. Second, in contrast to other trypanosomatids, the bloodstream form of T. brucei has a poorly developed mitochondrion, without a Krebs cycle and respiratory system coupled to ATP synthesis. Third, the glycolytic enzymes are particularlyabundant in this parasite, representing up to 90% of the glycosomal protein content8. Fourth, glycolytic flux in the bloodstream form of T. brucei is relatively high1,9. Finally, most of the glycosomal, non-glycolytic enzymes/pathways detected in other trypanosomatids are largely repressed in
Paul Michels and Véronique Hannaert are at the Research Unit for Tropical Diseases, Christian de DuveInstitute of Cellular Pathology, and Department of Biochemistry, Université Catholique de Louvain, Avenue Hippocrate 74, B-1200 Brussels, Belgium. Frédéric Bringaud is at the Laboratoire de Parasitologie Moléculaire, Université Victor Segalen, Bordeaux II, UMR-CNRS 5016, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. Tel: +32 2 764 74 73, Fax: +32 2 762 68 53, e-mail: michels@trop.ucl.ac.be 482this parasite. Thus, bloodstream-form T. brucei possesses a unique and much more simple energy metabolism than that of other trypanosomatids. The most characteristic features of this energy metabolism can be summarized as follows (see also Box 1). The glycolytic pathway is organized in such a way that the enzymes converting glucose into 3-phosphoglycerate are inside the glycosome, whereas the lastthree enzymes of the pathway reside in the cytosol1,5. As a consequence, net ATP synthesis occurs in the cytosol, in the reaction catalysed by pyruvate kinase (PYK), whereas in the glycosomes the consumption of ATP by hexokinase (HK) and phosphofructokinase (PFK) is balanced by ATP production by phosphoglycerate kinase (PGK). Similarly, no net change in the redox state of NAD(H) takes place in the...