The return of metabolism: biochemistry and physiology of the pentose phosphate pathway.
The return of metabolism: biochemistry and physiology of the pentose phosphate pathway.
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DOI：
10.1111/brv.12140
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发表时间：
2015-08
影响因子：
--
通讯作者：
Ralser M
中科院分区：
文献类型：
--
作者：
Stincone A;Prigione A;Cramer T;Wamelink MM;Campbell K;Cheung E;Olin-Sandoval V;Grüning NM;Krüger A;Tauqeer Alam M;Keller MA;Breitenbach M;Brindle KM;Rabinowitz JD;Ralser M
磷酸戊糖途径（PPP）是细胞代谢的基本组成部分。PPP对于维持碳稳态、提供核苷酸和氨基酸生物合成的前体、提供抗氧化剂的还原分子以及抵抗氧化应激是重要的。PPP与Entner-Doudoroff途径和卡尔文循环共享反应，并分为氧化和非氧化分支。氧化分支在大多数真核生物中高度活跃，并将葡萄糖6-磷酸转化为二氧化碳、核酮糖5-磷酸和NADPH。后一种功能对于在应激情况下维持氧化还原平衡至关重要，当细胞迅速增殖时，在衰老中，以及对于癌细胞的“瓦尔堡效应”。非氧化分支实际上是普遍存在的，并且代谢糖酵解中间体果糖6-磷酸和甘油醛3-磷酸以及景天庚酮糖糖，产生用于合成核酸的核糖5-磷酸和用于合成氨基酸的糖磷酸前体。而氧化PPP被认为是单向的，非氧化分支可以提供糖酵解与衍生自核糖5-磷酸的中间体，反之亦然，这取决于生化需求。这些功能需要PPP途径的动态调节，其通过转录组、蛋白质组和代谢组之间的分级相互作用来实现。因此，该途径的生物化学和调节虽然在许多情况下仍然未解决，但却是细胞代谢网络动力学的原型。在这篇综合性文章中，我们回顾了导致发现和描述该途径的开创性工作，该途径可以追溯到80年前，并讨论了有关调节其活性的遗传和代谢机制的最新结果。这些生物化学的原则进行了讨论的背景下，PPP缺陷导致代谢性疾病和生物技术，细菌和寄生虫感染，神经元，干细胞的潜力和癌症代谢的作用，这条途径。
The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism.
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DOI：
10.1126/science.1211485
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
通讯作者：
Cantley LC
影响因子：
5.4
作者：
Alteri CJ;Mobley HL
通讯作者：
Mobley HL
影响因子：
4.8
作者：
Banki, K;Hutter, E;Perl, A
通讯作者：
Perl, A
影响因子：
1.6
作者：
BARRETT, MP;PHILLIPS, C;LEPAGE, RWF
通讯作者：
LEPAGE, RWF
影响因子：
4.3
作者：
Achcar, Fiona;Kerkhoven, Eduard J.;Breitling, Rainer
通讯作者：
Breitling, Rainer