Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
FEBS J. 2013 Sep;280(18):4640-51. doi: 10.1111/febs.12436. Epub 2013 Aug 19.
Previous models of glycolysis in the sleeping sickness parasite Trypanosoma brucei assumed that the core part of glycolysis in this unicellular parasite is tightly compartimentalized within an organelle, the glycosome, which had previously been shown to contain most of the glycolytic enzymes. The glycosomes were assumed to be largely impermeable, and exchange of metabolites between the cytosol and the glycosome was assumed to be regulated by specific transporters in the glycosomal membrane. This tight compartmentalization was considered to be essential for parasite viability. Recently, size-specific metabolite pores were discovered in the membrane of glycosomes. These channels are proposed to allow smaller metabolites to diffuse across the membrane but not larger ones. In light of this new finding, we re-analyzed the model taking into account uncertainty about the topology of the metabolic system in T. brucei, as well as uncertainty about the values of all parameters of individual enzymatic reactions. Our analysis shows that these newly-discovered nonspecific pores are not necessarily incompatible with our current knowledge of the glycosomal metabolic system, provided that the known cytosolic activities of the glycosomal enzymes play an important role in the regulation of glycolytic fluxes and the concentration of metabolic intermediates of the pathway.
先前关于在睡眠病寄生虫布鲁氏锥虫中的糖酵解模型假设，糖酵解的核心部分在这个单细胞寄生虫中严格分隔在一个细胞器——糖蜜体（glycosome）内，先前的研究表明糖蜜体包含大部分糖酵解酶。糖蜜体被认为是基本上不可渗透的，细胞溶质和糖蜜体之间的代谢物交换被认为是由糖蜜体膜中的特定转运蛋白调节的。这种严格的分隔被认为对寄生虫的生存至关重要。最近，在糖蜜体的膜中发现了大小特异性代谢物孔。这些通道被认为允许较小的代谢物扩散穿过膜，但不允许较大的代谢物通过。鉴于这一新发现，我们重新分析了该模型，考虑了 T. brucei 中代谢系统拓扑结构的不确定性，以及单个酶反应所有参数值的不确定性。我们的分析表明，这些新发现的非特异性孔不一定与我们目前对糖蜜体代谢系统的了解相矛盾，只要已知的糖蜜体酶的细胞溶质活性在糖酵解通量和途径的代谢中间产物的浓度的调节中发挥重要作用。
