Lipid metabolism in Trypanosoma brucei

Abstract

Trypanosoma brucei membranes consist of all major eukaryotic glycerophospholipid and sphingolipid classes. These are de novo synthesized from precursors obtained either from the host or from catabolised endocytosed lipids. In recent years, substantial progress has been made in the molecular and biochemical characterisation of several of these lipid biosynthetic pathways, using gene knockout or RNA interference strategies or by enzymatic characterization of individual reactions. Together with the completed genome, these studies have highlighted several possible differences between mammalian and trypanosome lipid biosynthesis that could be exploited for the development of drugs against the diseases caused by these parasites.

Fig. 1

Phospholipid composition in T. brucei. Relative distribution of the phospholipid classes, PC, PE, PI, PS, and SM, in T. brucei procyclic and bloodstream forms. Others include IPC, EPC, CL, PG, PIPs, phosphatidic acid, lyso-phospholipids, phosphorylated prenyls, Dol-Ps.

Fig. 2

Predicted pathways for sphingolipid biosynthesis in T. brucei. Enzymes for which candidate genes have been identified in the T. brucei gene DB are indicated; see Table 1 for the abbreviations of the enzymes.

Fig. 3

Predicted pathways for glycerophospholipid biosynthesis in T. brucei. Enzymes for which candidate genes have been identified in the T. brucei gene DB are indicated; see Table 1 for the abbreviations of the enzymes.

Fig. 4

Pathway for GPI biosynthesis in T. brucei. Enzymes for which candidate genes have been identified in the T. brucei gene DB are indicated; see Table 1 for the abbreviations of the enzymes. BSF, bloodstream forms; PCF, procyclic forms.

Fig. 5

Predicted pathway for N-glycosylation in T. brucei. Enzymes for which candidate genes have been identified in the T. brucei gene DB are indicated; see Table 1 for the abbreviations of the enzymes.

Fig. 6

Predicted pathways for mevalonate and isoprenoid biosynthesis in T. brucei. Enzymes for which candidate genes have been identified in the T. brucei gene DB are indicated; see Table 1 for the abbreviations of the enzymes.