Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate

Rob C. Oslund, Xiaoyang Su, Michael Haugbro, Jung Min Kee, Mark Esposito, Yael David, Boyuan Wang, Eva Ge, David H. Perlman, Yibin Kang, Tom W. Muir, Joshua D. Rabinowitz

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1081-1087
Number of pages7
JournalNature Chemical Biology
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Oslund, R. C., Su, X., Haugbro, M., Kee, J. M., Esposito, M., David, Y., Wang, B., Ge, E., Perlman, D. H., Kang, Y., Muir, T. W., & Rabinowitz, J. D. (2017). Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate. Nature Chemical Biology, 13(10), 1081-1087. https://doi.org/10.1038/nchembio.2453