三羧酸(TCA)環(huán)是碳代謝的中樞,,將糖酵解,、糖異生、呼吸,、氨基酸合成及其他生物合成通道連接在一起,。
現(xiàn)在,瘧原蟲中的TCA代謝被發(fā)現(xiàn)在很大程度上與TCA糖酵解是沒有聯(lián)系的,,是沿一條根本不同的線路組織的,。在這種寄生蟲中,谷氨酰胺和谷氨酸鹽在一個(gè)分岔的而非環(huán)狀的通道中是TCA代謝的主要碳來源,。源自葡萄糖的碳在這個(gè)通道中幾乎是沒有的,。這些結(jié)果為有關(guān)瘧原蟲中基礎(chǔ)性的、中心性的碳代謝的很多長期未解現(xiàn)象提供了一個(gè)機(jī)制上的解釋,,并且也為抗瘧疾治療干預(yù)提出了新的目標(biāo),。(生物谷Bioon.com)
生物谷推薦原文出處:
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.