@article{119761,
  author = {LB Tanner and Goglia AG and Wei MH and Sehgal T and Parsons L and Park JO and White E and Toettcher JE and Rabinowitz J},
  title = {Flux control in mammalian glycolysis resides in a few key pathway steps},
  abstract = { <div class="content">
	<p>
		Altered glycolysis is a hallmark of diseases including diabetes and cancer. Despite intensive study of the contributions of individual glycolytic enzymes, systems-level analyses of flux control through glycolysis remain limited. Here, we overexpress in two mammalian cell lines the individual enzymes catalyzing each~of the 12 steps linking extracellular glucose to excreted lactate, and find substantial flux control at four steps: glucose import, hexokinase, phosphofructokinase, and lactate export (and not at any steps of lower glycolysis). The four flux-controlling steps are specifically upregulated by the Ras oncogene: optogenetic Ras activation rapidly induces the transcription of isozymes catalyzing these four steps and enhances glycolysis. At least one isozyme catalyzing each of these four steps is consistently elevated in human tumors. Thus, in the studied contexts, flux control in glycolysis is concentrated in four key enzymatic steps. Upregulation of these steps in tumors likely underlies the Warburg effect.
	</p>
</div>
 },
  year = {2018},
  journal = {Cell Systems},
  volume = {7},
  pages = {1-14},
  url = {https://www.cell.com/cell-systems/fulltext/S2405-4712(18)30243-6},
  language = {eng},
}