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Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.
PLOS Biology ( IF 9.8 ) Pub Date : 2021-08-13 , DOI: 10.1371/journal.pbio.3001359
Stefan Allmann 1, 2 , Marion Wargnies 1, 2 , Nicolas Plazolles 1 , Edern Cahoreau 3, 4 , Marc Biran 2 , Pauline Morand 2 , Erika Pineda 1 , Hanna Kulyk 3, 4 , Corinne Asencio 1 , Oriana Villafraz 1 , Loïc Rivière 1 , Emmanuel Tetaud 1 , Brice Rotureau 5 , Arnaud Mourier 6 , Jean-Charles Portais 3, 4, 7 , Frédéric Bringaud 1, 2
Affiliation  

Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, known as "catabolite repression," allowing redirection of cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism named "metabolic contest" for regulating the use of carbon sources without nutrient sensing and signaling. Trypanosoma brucei is a unicellular eukaryote transmitted by tsetse flies and causing human African trypanosomiasis, or sleeping sickness. We showed that, in contrast to most microorganisms, the insect stages of this parasite developed a preference for glycerol over glucose, with glucose consumption beginning after the depletion of glycerol present in the medium. This "metabolic contest" depends on the combination of 3 conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-related organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways both being ATP-dependent (glycerol kinase and hexokinase, respectively); and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being approximately 80-fold higher than the hexokinase activity. As predicted by our model, an approximately 50-fold down-regulation of the GK expression abolished the preference for glycerol over glucose, with glucose and glycerol being metabolized concomitantly. In theory, a metabolic contest could be found in any organism provided that the 3 conditions listed above are met.

中文翻译:

甘油通过代谢竞赛抑制锥虫中的葡萄糖消耗。

微生物必须做出正确的营养消耗选择以适应其不断变化的环境。因此,细菌和酵母已经发展出涉及营养传感和信号传导的调节机制,称为“分解代谢物抑制”,允许重新定向细胞代谢以最大限度地消耗节能碳源。在这里,我们报告了一种名为“代谢竞赛”的新机制,用于在没有营养感应和信号的情况下调节碳源的使用。布氏锥虫是一种单细胞真核生物,由采采蝇传播并导致人类非洲锥虫病或昏睡病。我们发现,与大多数微生物相比,这种寄生虫的昆虫阶段更偏爱甘油而不是葡萄糖,在培养基中存在的甘油耗尽后开始消耗葡萄糖。这种“代谢竞赛”取决于 3 个条件的组合:(i) 两种代谢途径在同一亚细胞区室中的隔离,这里是在称为糖体的过氧化物酶体相关细胞器中;(ii) 对相同底物的竞争,这里是 ATP,甘油和葡萄糖代谢途径的第一个酶促步骤都依赖于 ATP(分别为甘油激酶和己糖激酶);(iii) 竞争酶之间的活性不平衡,此处甘油激酶活性比己糖激酶活性高约 80 倍。正如我们的模型预测的那样,GK 表达的大约 50 倍下调消除了对甘油的偏好,而不是葡萄糖,葡萄糖和甘油同时代谢。理论上,只要满足上面列出的 3 个条件,就可以在任何生物体中发现代谢竞赛。
更新日期:2021-08-13
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