title: Rapid uptake and phosphorylation of D-mannose, and limited D-mannose 6-phosphate isomerization in the glycolytic pathway of bloodstream forms of Trypanosoma brucei gambiense.
abstract: Bloodstream forms of the parasitic protozoa Trypanosoma brucei gambiense derive all of needed energy through an unusual glycolysis. In an earlier study, we showed that D-mannose specifically inhibited the growth of bloodstream forms of T. b. gambiense. We investigated D-mannose transport into the T. b. gambiense bloodstream forms and its metabolism in the initial phase of the glycolytic pathway. D-Mannose was transported rapidly into the bloodstream forms of T. b. gambiense (K(m) = 378 microM), and D-glucose competitively inhibited D-mannose uptake. D-Mannose and D-glucose are transported into bloodstream trypanosomes by the same carrier. Hexokinase from the bloodstream trypanosomes could convert D-mannose to D-mannose 6-phosphate (K(m) = 155.8 microM; Vmax = 0.93 mumol/min/mg protein); with kinetic properties very similar to D-glucose phosphorylation (K(m) = 199.4 microM; Vmax = 1.15 mumol/min/mg protein). D-Mannose 6-phosphate could be further metabolized in the glycolytic pathway. However, the metabolic rate was extremely slow, and D-mannose 6-phosphate accumulated in the glycosomes. D-Mannose may cause growth inhibition of bloodstream trypanosomes through an extremely high concentration of D-mannose 6-phosphate in the glycosomes.
authors.affiliation: Department of Parasitology, Kurume University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Kanbara
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.forename: T
authors.initials: T
authors.lastname: Fukuma
mesh_terms: D000818:Animals; D001692:Biological Transport; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D008358:Mannose / Q000378:metabolism*; D008360:Mannosephosphates / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D010766:Phosphorylation; D014347:Trypanosoma brucei gambiense / Q000378:metabolism*
chemical_list: D008360:Mannosephosphates; C027693:mannose-6-phosphate; D010695:Phlorhizin; D006593:Hexokinase; D008358:Mannose