Bringaud Frédéric, Biran Marc, Millerioux Yoann, Wargnies Marion, Allmann Stefan, Mazet Muriel
Centre de Résonance Magnétique des Systèmes Biologiques, UMR-5536 Université de Bordeaux, CNRS, 146 rue Léo Saignat, 33076, Bordeaux, France.
Mol Microbiol. 2015 Jun;96(5):917-26. doi: 10.1111/mmi.12990. Epub 2015 Apr 7.
Numerous eukaryotes have developed specific metabolic traits that are not present in extensively studied model organisms. For instance, the procyclic insect form of Trypanosoma brucei, a parasite responsible for sleeping sickness in its mammalian-specific bloodstream form, metabolizes glucose into excreted succinate and acetate through pathways with unique features. Succinate is primarily produced from glucose-derived phosphoenolpyruvate in peroxisome-like organelles, also known as glycosomes, by a soluble NADH-dependent fumarate reductase only described in trypanosomes so far. Acetate is produced in the mitochondrion of the parasite from acetyl-CoA by a CoA-transferase, which forms an ATP-producing cycle with succinyl-CoA synthetase. The role of this cycle in ATP production was recently demonstrated in procyclic trypanosomes and has only been proposed so far for anaerobic organisms, in addition to trypanosomatids. We review how nuclear magnetic resonance spectrometry can be used to analyze the metabolic network perturbed by deletion (knockout) or downregulation (RNAi) of the candidate genes involved in these two particular metabolic pathways of procyclic trypanosomes. The role of succinate and acetate production in trypanosomes is discussed, as well as the connections between the succinate and acetate branches, which increase the metabolic flexibility probably required by the parasite to deal with environmental changes such as oxidative stress.
许多真核生物已经发展出了一些特定的代谢特性，而这些特性在经过广泛研究的模式生物中并不存在。例如，布氏锥虫的前循环型昆虫形态，这种寄生虫在其哺乳动物特异性血液形态中会导致昏睡病，它通过具有独特特征的途径将葡萄糖代谢为分泌的琥珀酸和乙酸。琥珀酸主要由葡萄糖衍生的磷酸烯醇丙酮酸在过氧化物酶体样细胞器（也称为糖体）中通过一种迄今为止仅在锥虫中描述过的可溶性NADH依赖性延胡索酸还原酶产生。乙酸则是由寄生虫线粒体中的乙酰辅酶A通过一种辅酶A转移酶产生的，该酶与琥珀酰辅酶A合成酶形成一个产生ATP的循环。最近在布氏锥虫前循环型中证明了这个循环在ATP产生中的作用，并且到目前为止，除了锥虫外，仅在厌氧生物中有所提及。我们综述了如何利用核磁共振光谱法来分析参与布氏锥虫前循环型这两种特定代谢途径的候选基因缺失（敲除）或下调（RNA干扰）所扰乱的代谢网络。文中讨论了琥珀酸和乙酸产生在锥虫中的作用，以及琥珀酸和乙酸分支之间的联系，这些联系增加了寄生虫应对环境变化（如氧化应激）可能所需的代谢灵活性。
