New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle
New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle
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DOI：
10.1074/jbc.m412447200
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发表时间：
2005-04-01
影响因子：
4.8
通讯作者：
Tielens, AGM
中科院分区：
文献类型：
--
作者：
van Weelden, SWH;van Hellemond, JJ;Tielens, AGM
我们研究了底物可用性是否影响前循环布氏锥虫的能量代谢类型。我们表明，缺乏糖酵解底物（葡萄糖和甘油）不会引起从发酵代谢到底物完全氧化的转变。我们还表明，葡萄糖（甚至糖酵解）对于多形性原环布氏T. brucei细胞的正常功能和增殖并不是必需的。此外，缺乏葡萄糖不会导致氨基酸降解增加。然而，葡萄糖和甘油可用性的变化确实导致代谢适应，使得糖体始终处于氧化还原平衡。我们认为，在原循环细胞中，磷酸甘油酸激酶可能不仅位于细胞质中，而且还位于糖体内，否则该细胞器中会出现 ATP 缺乏。我们证明，前环T. brucei 使用克雷布斯循环的一部分来实现线粒体底物完全降解以外的目的。我们建议使用柠檬酸合酶加上丙酮酸脱氢酶和苹果酸脱氢酶将乙酰辅酶A单位从线粒体转运到胞质溶胶以进行脂肪酸的生物合成，我们证明这一过程发生在增殖的原循环细胞中。由α-酮戊二酸脱氢酶和琥珀酰辅酶A合成酶组成的克雷布斯循环部分用于将脯氨酸和谷氨酸降解为琥珀酸。我们还证明，克雷布斯循环的后续酶，琥珀酸脱氢酶和延胡索酸酶，最有可能用于将琥珀酸转化为苹果酸，然后可用于糖异生。
We investigated whether substrate availability influences the type of energy metabolism in procyclic Trypanosoma brucei. We show that absence of glycolytic substrates ( glucose and glycerol) does not induce a shift from a fermentative metabolism to complete oxidation of substrates. We also show that glucose ( and even glycolysis) is not essential for normal functioning and proliferation of pleomorphic procyclic T. brucei cells. Furthermore, absence of glucose did not result in increased degradation of amino acids. Variations in availability of glucose and glycerol did result, however, in adaptations in metabolism in such a way that the glycosome was always in redox balance. We argue that it is likely that, in procyclic cells, phosphoglycerate kinase is located not only in the cytosol, but also inside glycosomes, as otherwise an ATP deficit would occur in this organelle. We demonstrate that procyclic T. brucei uses parts of the Krebs cycle for purposes other than complete degradation of mitochondrial substrates. We suggest that citrate synthase plus pyruvate dehydrogenase and malate dehydrogenase are used to transport acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, a process we show to occur in proliferating procyclic cells. The part of the Krebs cycle consisting of alpha-ketoglutarate dehydrogenase and succinylCoA synthetase was used for the degradation of proline and glutamate to succinate. We also demonstrate that the subsequent enzymes of the Krebs cycle, succinate dehydrogenase and fumarase, are most likely used for conversion of succinate into malate, which can then be used in gluconeogenesis.