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Serine is a natural ligand and allosteric activator of pyruvate kinase M2.

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.

SUBMITTER: Chaneton B

PROVIDER: S-EPMC3894725 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Serine is a natural ligand and allosteric activator of pyruvate kinase M2.

Chaneton Barbara B Hillmann Petra P Zheng Liang L Martin Agnès C L ACL Maddocks Oliver D K ODK Chokkathukalam Achuthanunni A Coyle Joseph E JE Jankevics Andris A Holding Finn P FP Vousden Karen H KH Frezza Christian C O'Reilly Marc M Gottlieb Eyal E

Nature 20121014 7424

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 acti ...[more]

PMID: 23064226

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Synergistic Allosteric Mechanism of Fructose-1,6-bisphosphate and Serine for Pyruvate Kinase M2 via Dynamics Fluctuation Network Analysis.

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| S-EPMC9655700 | biostudies-literature

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| S-EPMC3005776 | biostudies-literature

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