来自英国比森癌症研究所的科学家研究表明丝氨酸是M2型丙酮酸激酶的一种天然配体和变构激活剂。

-2012年11月15日《自然》

中文翻译


【题目】丝氨酸是丙酮酸激酶M2的一种天然配体和变构激活剂

【译文】癌细胞表现出一些独特的代谢规律,这些代谢规律对于细胞生长和增殖至关重要。尤其是,它们会使得可以控制糖酵解通量且受严格调控的酶丙酮酸激酶M2亚型(PKM2)过表达,而且这高度依赖丝氨酸和甘氨酸的从头合成。本研究描述了PKM2活性和丝氨酸生物合成之间的一种新的变阻器样机制关系。研究表明丝氨酸可以结合并激活人类PKM2,并表明当应答丝氨酸饥饿时细胞中PKM2活性减少了。PKM2活性的减少会使细胞转换成燃料效率模式,在该模式中更多的丙酮酸被转入到线粒体中而且更多来源于葡萄糖的碳原子被运输到丝氨酸生物合成过程以支持细胞增殖。

英文原稿


[Title]: Serine is a natural ligand and allosteric activator of pyruvate kinase M2

[Authors]:Barbara Chaneton,1, 5 Petra Hillmann,2, 5 Liang Zheng,1 Agnès C. L. Martin,2 Oliver D. K. Maddocks,1 Achuthanunni Chokkathukalam,3 Joseph E. Coyle,2 Andris Jankevics,3, 4 Finn P. Holding,2 Karen H. Vousden,1 Christian Frezza,1,6 Marc O’Reilly2 & Eyal Gottlieb1

[Abstract]Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.

原文地址

http://www.nature.com/nature/journal/v491/n7424/full/nature11540.html

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