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.
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.
Hara
T
T
Department of Parasitology, Kurume University School of Medicine, Japan.
Kanbara
H
H
Nakao
M
M
Fukuma
T
T
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*
D008360:Mannosephosphates; C027693:mannose-6-phosphate; D010695:Phlorhizin; D006593:Hexokinase; D008358:Mannose