PDF(Pubmed)
Abstract：
Glycolysis is the central metabolic pathway across all kingdoms of life. Intensive research efforts have been devoted to understanding the tightly orchestrated processes of converting glucose into energy in health and disease. Our review highlights the advances in knowledge of how metabolic and gene networks are integrated through the precise spatiotemporal compartmentalization of rate-limiting enzymes. We provide an overview of technically innovative approaches that have been applied to study phosphofructokinase-1 (PFK1), which represents the fate-determining step of oxidative glucose metabolism. Specifically, we discuss fast-acting chemical biology and optogenetic tools that have delineated new links between metabolite fluxes and transcriptional reprogramming, which operate together to enact tissue-specific processes. Finally, we discuss how recent paradigm-shifting insights into the fundamental basis of glycolytic regulatory control have shed light on the mechanisms of tumorigenesis and could provide insight into new therapeutic vulnerabilities in cancer.
摘要：
糖酵解是贯穿所有生命王国的中心代谢途径。深入的研究工作已经致力于理解在健康和疾病中将葡萄糖转化为能量的紧密协调的过程。我们的评论强调了如何通过限速酶的精确时空分隔整合代谢和基因网络的知识方面的进步。我们提供了已应用于研究磷酸果糖激酶-1（PFK1）的技术创新方法的概述，这代表了氧化葡萄糖代谢的命运决定步骤。具体来说,我们讨论了速效化学生物学和光遗传学工具，它们描绘了代谢物通量和转录重编程之间的新联系，它们一起运行以制定组织特定的过程。最后,我们讨论了最近对糖酵解调节控制的基本基础的范式转变的见解如何阐明了肿瘤发生的机制，并可以提供对癌症新的治疗脆弱性的见解。
