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Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate.

Author(s): Oslund, Rob C; Su, Xiaoyang; Haugbro, Michael; Kee, Jung-Min; Esposito, Mark; et al

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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.
Publication Date: Oct-2017
Citation: 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. (2017). Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate.. Nature chemical biology, 13 (10), 1081 - 1087. doi:10.1038/nchembio.2453
DOI: doi:10.1038/nchembio.2453
ISSN: 1552-4450
EISSN: 1552-4469
Pages: 1081 - 1087
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Nature chemical biology

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