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Nat Chem Biol. 2017 Oct;13(10):1081-1087. doi: 10.1038/nchembio.2453. Epub 2017 Aug 7.

Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate.

Author information

1
Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
2
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
3
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
4
Graduate Program, The Rockefeller University, New York, New York, USA.

Abstract

Lower glycolysis involves a series of reversible reactions, which interconvert intermediates that also feed anabolic pathways. 3-phosphoglycerate (3-PG) is an abundant lower glycolytic intermediate that feeds serine biosynthesis via the enzyme phosphoglycerate dehydrogenase, which is genomically amplified in several cancers. Phosphoglycerate mutase 1 (PGAM1) catalyzes the isomerization of 3-PG into the downstream glycolytic intermediate 2-phosphoglycerate (2-PG). PGAM1 needs to be histidine phosphorylated to become catalytically active. We show that the primary PGAM1 histidine phosphate donor is 2,3-bisphosphoglycerate (2,3-BPG), which is made from the glycolytic intermediate 1,3-bisphosphoglycerate (1,3-BPG) by bisphosphoglycerate mutase (BPGM). When BPGM is knocked out, 1,3-BPG can directly phosphorylate PGAM1. In this case, PGAM1 phosphorylation and activity are decreased, but nevertheless sufficient to maintain normal glycolytic flux and cellular growth rate. 3-PG, however, accumulates, leading to increased serine synthesis. Thus, one biological function of BPGM is controlling glycolytic intermediate levels and thereby serine biosynthetic flux.

PMID:
28805803
PMCID:
PMC5605442
DOI:
10.1038/nchembio.2453
[Indexed for MEDLINE]
Free PMC Article

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