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Control and regulation of the pyrophosphate-dependent glucose metabolism in Entamoeba histolytica.
Molecular and Biochemical Parasitology ( IF 1.5 ) Pub Date : 2019-02-14 , DOI: 10.1016/j.molbiopara.2019.02.002
Emma Saavedra 1 , Rusely Encalada 1 , Citlali Vázquez 1 , Alfonso Olivos-García 2 , Paul A M Michels 3 , Rafael Moreno-Sánchez 1
Affiliation  

Entamoeba histolytica has neither Krebs cycle nor oxidative phosphorylation activities; therefore, glycolysis is the main pathway for ATP supply and provision of carbon skeleton precursors for the synthesis of macromolecules. Glucose is metabolized through fermentative glycolysis, producing ethanol as its main end-product as well as some acetate. Amoebal glycolysis markedly differs from the typical Embden-Meyerhof-Parnas pathway present in human cells: (i) by the use of inorganic pyrophosphate, instead of ATP, as the high-energy phospho group donor; (ii) with one exception, the pathway enzymes can catalyze reversible reactions under physiological conditions; (iii) there is no allosteric regulation and sigmoidal kinetic behavior of key enzymes; and (iv) the presence of some glycolytic and fermentation enzymes similar to those of anaerobic bacteria. These peculiarities bring about alternative mechanisms of control and regulation of the PPi-dependent fermentative glycolysis in the parasite in comparison to the ATP-dependent and allosterically regulated glycolysis in many other eukaryotic cells. In this review, the current knowledge of the carbohydrate metabolism enzymes in E. histolytica is analyzed. Thermodynamics and stoichiometric analyses indicate 2 to 3.5 ATP yield per glucose metabolized, instead of the often presumed 5 ATP/glucose ratio. PPi derived from anabolism seems insufficient for PPi-glycolysis; hence, alternative ways of PPi supply are also discussed. Furthermore, the underlying mechanisms of control and regulation of the E. histolytica carbohydrate metabolism, analyzed by applying integral and systemic approaches such as Metabolic Control Analysis and kinetic modeling, contribute to unveiling alternative and promising drug targets.



中文翻译:

溶血性变形虫中焦磷酸盐依赖性葡萄糖代谢的控制和调节。

溶组织性变形虫没有克雷布斯循环,也没有氧化磷酸化活性;因此,糖酵解是ATP供给和提供碳骨架前体以合成大分子的主要途径。葡萄糖通过发酵糖酵解代谢,产生乙醇作为其主要终产物以及一些乙酸盐。阿米巴糖酵解明显不同于人细胞中典型的Embden-Meyerhof-Parnas途径:(i)通过使用无机焦磷酸盐代替ATP作为高能磷酸基团供体;(ii)除一个例外,途径酶可以在生理条件下催化可逆反应;(iii)关键酶没有变构调节和S形动力学行为;(iv)存在一些类似于厌氧细菌的糖酵解和发酵酶。与许多其他真核细胞中的ATP依赖性和变构调节的糖酵解相比,这些特性带来了寄生虫中PPi依赖性发酵糖酵解的控制和调节机制。在这篇评论中,当前关于碳水化合物代谢酶的知识分析溶组织性大肠杆菌。热力学和化学计量分析表明,每个代谢的葡萄糖产生2至3.5 ATP的产量,而不是通常假定的5 ATP /葡萄糖比率。合成代谢产生的PPi似乎不足以进行PPi糖酵解。因此,还讨论了PPi供应的替代方式。此外,通过应用整体和系统性方法(例如代谢控制分析和动力学建模)分析的溶组织性肠埃希氏菌碳水化合物代谢的基本控制机制有助于揭示替代性和有希望的药物靶标。

更新日期:2019-02-14
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