Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate

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

doi:10.1038/nchembio.2453

Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate

Journal Article · Mon Aug 07 00:00:00 EDT 2017 · Nature Chemical Biology

DOI:https://doi.org/10.1038/nchembio.2453· OSTI ID:1546615

Oslund, Rob C. ^[1]; Su, Xiaoyang ^[2]; Haugbro, Michael ^[3]; ^[2]; Esposito, Mark ^[3]; David, Yael ^[2]; Wang, Boyuan ^[4]; Ge, Eva ^[3]; Perlman, David H. ^[3]; Kang, Yibin ^[3]; Muir, Tom W. ^[3]; Rabinowitz, Joshua D. ^[3]

Princeton Univ., NJ (United States); Merck Research Lab., Cambridge, MA (United States); Rutgers Univ., New Brunswick, NJ (United States); Ulsan National Institute of Science and Technology (UNIST) (Korea); Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); None
Princeton Univ., NJ (United States); Merck Research Lab., Cambridge, MA (United States); Rutgers Univ., New Brunswick, NJ (United States); Ulsan National Institute of Science and Technology (UNIST) (Korea); Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Princeton Univ., NJ (United States)
Princeton Univ., NJ (United States); Merck Research Lab., Cambridge, MA (United States); Rutgers Univ., New Brunswick, NJ (United States); Ulsan National Institute of Science and Technology (UNIST) (Korea); Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Rockefeller Univ., New York, NY (United States)

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. Here, this work shows 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 nonetheless sufficient to maintain normal glycolytic flux and cellular growth rate. 3-PG, however, accumulates, leading to increased serine synthesis. Hence, one biological function of BPGM is controlling glycolytic intermediate levels and thereby serine biosynthetic flux.

View Accepted Manuscript (DOE)

Research Organization:: Princeton Univ., NJ (United States)

Sponsoring Organization:: Damon Runyon Cancer Research Foundation; National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: SC0012461

OSTI ID:: 1546615

Alternate ID(s):: OSTI ID: 1539779

Journal Information:: Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 10 Vol. 13; ISSN 1552-4450

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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