Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate.

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 Aug 07
ISSN1552-4469
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.

DOI10.1038/nchembio.2453
Alternate JournalNat. Chem. Biol.
PubMed ID28805803
Grant ListR01 GM095880 / GM / NIGMS NIH HHS / United States