Organization of enzyme concentration across the metabolic network in cancer cells.
Organization of enzyme concentration across the metabolic network in cancer cells.
复制标题
DOI：
10.1371/journal.pone.0117131
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Locasale JW
中科院分区：
文献类型：
--
作者：
Madhukar NS;Warmoes MO;Locasale JW
质谱技术的快速发展使得人们可以估计整个蛋白质组的绝对浓度，从而可以解决许多重要的生物学问题。在这里，我们专注于人类癌细胞代谢的定量方面，这受到代谢酶丰度的可用数据缺乏的限制。我们整合了最近测量的绝对蛋白质浓度数据，以分析整个人类代谢网络中蛋白质丰度的统计数据。在全球范围内，我们发现糖酵解中的酶约占代谢蛋白总量的一半，并可占整个蛋白质组的10%。然后，我们使用这种分析来研究癌症代谢中的几个突出问题，包括糖酵解通量的生物合成的转向，氮同化途径的相对贡献，以及细胞氧化还原电位的起源。我们发现了与当前模型的许多一致性，发现了几个不一致之处，并发现了超出当前理解的普遍性。总之，我们的结果表明，对代谢酶丰度的相对简单的分析能够揭示对人类癌细胞代谢网络组织的许多见解。
Rapid advances in mass spectrometry have allowed for estimates of absolute concentrations across entire proteomes, permitting the interrogation of many important biological questions. Here, we focus on a quantitative aspect of human cancer cell metabolism that has been limited by a paucity of available data on the abundance of metabolic enzymes. We integrate data from recent measurements of absolute protein concentration to analyze the statistics of protein abundance across the human metabolic network. At a global level, we find that the enzymes in glycolysis comprise approximately half of the total amount of metabolic proteins and can constitute up to 10% of the entire proteome. We then use this analysis to investigate several outstanding problems in cancer metabolism, including the diversion of glycolytic flux for biosynthesis, the relative contribution of nitrogen assimilating pathways, and the origin of cellular redox potential. We find many consistencies with current models, identify several inconsistencies, and find generalities that extend beyond current understanding. Together our results demonstrate that a relatively simple analysis of the abundance of metabolic enzymes was able to reveal many insights into the organization of the human cancer cell metabolic network.
登录
查看更多内容
影响因子：
64.8
作者：
Kim, Min-Sik;Pinto, Sneha M.;Getnet, Derese;Nirujogi, Raja Sekhar;Manda, Srikanth S.;Chaerkady, Raghothama;Madugundu, Anil K.;Kelkar, Dhanashree S.;Isserlin, Ruth;Jain, Shobhit;Thomas, Joji K.;Muthusamy, Babylakshmi;Leal-Rojas, Pamela;Kumar, Praveen;Sahasrabuddhe, Nandini A.;Balakrishnan, Lavanya;Advani, Jayshree;George, Bijesh;Renuse, Santosh;Selvan, Lakshmi Dhevi N.;Patil, Arun H.;Nanjappa, Vishalakshi;Radhakrishnan, Aneesha;Prasad, Samarjeet;Subbannayya, Tejaswini;Raju, Rajesh;Kumar, Manish;Sreenivasamurthy, Sreelakshmi K.;Marimuthu, Arivusudar;Sathe, Gajanan J.;Chavan, Sandip;Datta, Keshava K.;Subbannayya, Yashwanth;Sahu, Apeksha;Yelamanchi, Soujanya D.;Jayaram, Savita;Rajagopalan, Pavithra;Sharma, Jyoti;Murthy, Krishna R.;Syed, Nazia;Goel, Renu;Khan, Aafaque A.;Ahmad, Sartaj;Dey, Gourav;Mudgal, Keshav;Chatterjee, Aditi;Huang, Tai-Chung;Zhong, Jun;Wu, Xinyan;Shaw, Patrick G.;Freed, Donald;Zahari, Muhammad S.;Mukherjee, Kanchan K.;Shankar, Subramanian;Mahadevan, Anita;Lam, Henry;Mitchell, Christopher J.;Shankar, Susarla Krishna;Satishchandra, Parthasarathy;Schroeder, John T.;Sirdeshmukh, Ravi;Maitra, Anirban;Leach, Steven D.;Drake, Charles G.;Halushka, Marc K.;Prasad, T. S. Keshava;Hruban, Ralph H.;Kerr, Candace L.;Bader, Gary D.;Iacobuzio-Donahue, Christine A.;Gowda, Harsha;Pandey, Akhilesh
通讯作者：
Pandey, Akhilesh
癌细胞对葡萄糖限制和双胍类药物敏感性的代谢决定因素。
影响因子：
64.8
作者：
Birsoy, Kivanc;Possemato, Richard;Lorbeer, Franziska K.;Bayraktar, Erol C.;Thiru, Prathapan;Yucel, Burcu;Wang, Tim;Chen, Walter W.;Clish, Clary B.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
5.4
作者：
Dang CV
通讯作者：
Dang CV
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
7
作者：
Chen, GA;Gharib, TG;Beer, DG
通讯作者：
Beer, DG