Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation.
Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation.
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DOI：
10.1371/journal.pone.0025881
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Oltvai ZN
中科院分区：
文献类型：
--
作者：
Vazquez A;Markert EK;Oltvai ZN
先前的实验证据表明，一些癌细胞具有净零ATP产生的替代糖酵解途径，这意味着这些细胞中糖酵解的上调可能与ATP的产生无关。在这里，我们使用人类细胞代谢的基因组规模模型来研究使用净零ATP糖酵解的细胞中的潜在代谢改变。我们发现了一种新的途径ATP生成，涉及丝氨酸生物合成，一碳代谢和甘氨酸裂解系统的反应，并表明该途径是转录上调的诱导型小鼠模型Myc驱动的肝肿瘤发生。该途径在使用净零ATP糖酵解的细胞中具有比使用标准糖酵解的细胞高两倍的预测通量率，并且产生两倍的ATP，乳酸的速率显著降低，但丙氨酸的分泌速率较高。因此，在使用标准或净零ATP糖酵解途径的细胞中，糖酵解通量的显著部分总是与ATP产生相关，并且两种途径的通量速率之间的比率决定了糖酵解期间ATP产生以及乳酸和丙氨酸分泌的速率。
Previous experimental evidence indicates that some cancer cells have an alternative glycolysis pathway with net zero ATP production, implying that upregulation of glycolysis in these cells may not be related to the generation of ATP. Here we use a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. We uncover a novel pathway for ATP generation that involves reactions from serine biosynthesis, one-carbon metabolism and the glycine cleavage system, and show that the pathway is transcriptionally upregulated in an inducible murine model of Myc-driven liver tumorigenesis. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate - but higher rate of alanine secretion. Thus, in cells using the standard - or the net zero ATP glycolysis pathways a significant portion of the glycolysis flux is always associated with ATP generation, and the ratio between the flux rates of the two pathways determines the rate of ATP generation and lactate and alanine secretion during glycolysis.
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影响因子：
4
作者：
EICHLER, HG;HUBBARD, R;SNELL, K
通讯作者：
SNELL, K
影响因子：
29
作者：
Hu S;Balakrishnan A;Bok RA;Anderton B;Larson PE;Nelson SJ;Kurhanewicz J;Vigneron DB;Goga A
通讯作者：
Goga A
影响因子：
64.8
作者：
Possemato, Richard;Marks, Kevin M.;Shaul, Yoav D.;Pacold, Michael E.;Kim, Dohoon;Birsoy, Kivanc;Sethumadhavan, Shalini;Woo, Hin-Koon;Jang, Hyun G.;Jha, Abhishek K.;Chen, Walter W.;Barrett, Francesca G.;Stransky, Nicolas;Tsun, Zhi-Yang;Cowley, Glenn S.;Barretina, Jordi;Kalaany, Nada Y.;Hsu, Peggy P.;Ottina, Kathleen;Chan, Albert M.;Yuan, Bingbing;Garraway, Levi A.;Root, David E.;Mino-Kenudson, Mari;Brachtel, Elena F.;Driggers, Edward M.;Sabatini, David M.
通讯作者：
Sabatini, David M.
DOI：
10.1152/ajplung.00274.2009
发表时间：
2010-10-01
影响因子：
4.9
作者：
Parra-Bonilla, Glenda;Alvarez, Diego F.;Stevens, Troy
通讯作者：
Stevens, Troy
DOI：
10.1126/science.1188015
发表时间：
2010-09-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Vander Heiden MG;Locasale JW;Swanson KD;Sharfi H;Heffron GJ;Amador-Noguez D;Christofk HR;Wagner G;Rabinowitz JD;Asara JM;Cantley LC
通讯作者：
Cantley LC