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
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
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DOI:
10.2739/kurumemedj.44.105
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发表时间:
1997-01-01
影响因子:
--
通讯作者:
Fukuma, Toshihide
中科院分区:
文献类型:
--
作者:
Hara, Tatsuru;Kanbara, Hiroji;Fukuma, Toshihide
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 mu-M), 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 mu-M; V-max = 0.93 mu-mol/min/mg protein), with kinetic properties very similar to D-glucose phosphorylation (K-m = 199.4 mu-M; V-max = 1.15 mu-mol/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.