Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate
- 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.
- Research Organization:
- Princeton Univ., NJ (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Damon Runyon Cancer Research Foundation
- Grant/Contract Number:
- SC0012461
- OSTI ID:
- 1546615
- Journal Information:
- Nature Chemical Biology, Vol. 13, Issue 10; ISSN 1552-4450
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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