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Nature:疟原虫的TCA代谢机制

来源:Nature 2010-08-06 13:36

三羧酸(TCA)环是碳代谢的中枢,将糖酵解、糖异生、呼吸、氨基酸合成及其他生物合成通道连接在一起。

现在,疟原虫中的TCA代谢被发现在很大程度上与TCA糖酵解是没有联系的,是沿一条根本不同的线路组织的。在这种寄生虫中,谷氨酰胺和谷氨酸盐在一个分岔的而非环状的通道中是TCA代谢的主要碳来源。源自葡萄糖的碳在这个通道中几乎是没有的。这些结果为有关疟原虫中基础性的、中心性的碳代谢的很多长期未解现象提供了一个机制上的解释,并且也为抗疟疾治疗干预提出了新的目标。(生物谷Bioon.com)

生物谷推荐原文出处:

Nature doi:10.1038/nature09301

Branched tricarboxylic acid metabolism in Plasmodium falciparum
Kellen L. Olszewski,Michael W. Mather,Joanne M. Morrisey,Benjamin A. Garcia,Akhil B. Vaidya,Joshua D. Rabinowitz& Manuel Llinás

A central hub of carbon metabolism is the tricarboxylic acid cycle1, which serves to connect the processes of glycolysis, gluconeogenesis, respiration, amino acid synthesis and other biosynthetic pathways. The protozoan intracellular malaria parasites (Plasmodium spp.), however, have long been suspected of possessing a significantly streamlined carbon metabolic network in which tricarboxylic acid metabolism plays a minor role2. Blood-stage Plasmodium parasites rely almost entirely on glucose fermentation for energy and consume minimal amounts of oxygen3, yet the parasite genome encodes all of the enzymes necessary for a complete tricarboxylic acid cycle4. Here, by tracing 13C-labelled compounds using mass spectrometry5 we show that tricarboxylic acid metabolism in the human malaria parasite Plasmodium falciparum is largely disconnected from glycolysis and is organized along a fundamentally different architecture from the canonical textbook pathway. We find that this pathway is not cyclic, but rather is a branched structure in which the major carbon sources are the amino acids glutamate and glutamine. As a consequence of this branched architecture, several reactions must run in the reverse of the standard direction, thereby generating two-carbon units in the form of acetyl-coenzyme A. We further show that glutamine-derived acetyl-coenzyme A is used for histone acetylation, whereas glucose-derived acetyl-coenzyme A is used to acetylate amino sugars. Thus, the parasite has evolved two independent production mechanisms for acetyl-coenzyme A with different biological functions. These results significantly clarify our understanding of the Plasmodium metabolic network and highlight the ability of altered variants of central carbon metabolism to arise in response to unique environments.

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