Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate
| Autor: | Mark Esposito, Xiaoyang Su, David H. Perlman, Joshua D. Rabinowitz, Yael David, Michael Haugbro, Rob C. Oslund, Jung-Min Kee, Yibin Kang, Eva J. Ge, Tom W. Muir, Boyuan Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glyceric Acids Article Serine Phosphoglycerate mutase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biosynthesis Phosphoglycerate Mutase 1 Tumor Cells Cultured Humans Phosphoglycerate dehydrogenase Molecular Biology Bisphosphoglycerate mutase Phosphoglycerate Mutase Phosphoglycerate kinase biology Cell Biology Phosphoglycerate Mutase Deficiency 030104 developmental biology Biochemistry chemistry 030220 oncology & carcinogenesis biology.protein |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | 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 (PGAM1) catalyzes the isomerization of 3-PG into the downstream glycolytic intermediate 2-phosphoglycerate (2-PG). Catalytic activity of PGAM1 requires its histidine phosphorylation. 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 to control glycolytic intermediate levels and thereby serine biosynthetic flux. Graphical Abstract |
| Databáze: | OpenAIRE |
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