TitleBisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate.
Publication TypeJournal Article
Year of Publication2017
AuthorsOslund, RC, Su, X, Haugbro, M, Kee, J-M, Esposito, M, David, Y, Wang, B, Ge, E, Perlman, DH, Kang, Y, Muir, TW, Rabinowitz, JD
JournalNat Chem Biol
Date Published2017 Oct
KeywordsGlyceric Acids, Humans, Phosphoglycerate Mutase, Serine, Tumor Cells, Cultured

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.

Alternate JournalNat. Chem. Biol.
PubMed ID28805803
PubMed Central IDPMC5605442
Grant ListF32 CA167901 / CA / NCI NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
R01 CA163591 / CA / NCI NIH HHS / United States
R01 GM095880 / GM / NIGMS NIH HHS / United States