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
Fukuma, Toshihide
中科院分区:
其他
文献类型:
--
作者:
Hara, Tatsuru;Kanbara, Hiroji;Fukuma, Toshihide

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血流形式的寄生原生动物布氏冈比亚锥虫通过一种不同寻常的糖酵解获得所有所需的能量。在早期的一项研究中,我们发现D-甘露糖特异性地抑制冈比亚弓形虫的血液生长。我们研究了D-甘露糖在冈比亚结核杆菌血液中的转运及其在糖酵解途径初始阶段的代谢。D-甘露糖被迅速转运到冈比亚锥虫(K-m=378 mU-M)的血液中,D-葡萄糖竞争性地抑制了D-甘露糖的摄取。D-甘露糖和D-葡萄糖通过同一载体转运到血流锥虫体内。来自血液锥体的己糖激酶能将D-甘露糖转化为D-甘露糖6-磷酸(K-m=155.8 mU-M;V-max=0.93mU-m o l/m in/mg蛋白),其动力学性质与D-葡萄糖磷酸化非常相似(K-m=199.4 m u-M;V-m ax=1.15m u-m o l/m in/mg蛋白)。D-甘露糖6-磷酸可在糖酵解途径中进一步代谢。然而,代谢速度非常慢,D-甘露糖6-磷酸积累在糖体中。D-甘露糖可能通过糖体中浓度极高的D-甘露糖6-磷酸抑制血流锥体的生长。
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.