Serine synthesis through PHGDH coordinates nucleotide levels by maintaining central carbon metabolism
Metabolic pathway
Serine hydroxymethyltransferase
DOI:
10.1038/s41467-018-07868-6
Publication Date:
2018-12-17T16:32:41Z
AUTHORS (12)
ABSTRACT
Phosphoglycerate dehydrogenase (PHGDH) catalyzes the committed step in de novo serine biosynthesis. Paradoxically, PHGDH and synthesis are required presence of abundant environmental even when uptake exceeds requirements for nucleotide synthesis. Here, we establish a mechanism how maintains metabolism. We show that inhibition induces alterations metabolism independent utilization. These changes not attributable to defects serine-derived redox maintenance, another key aspect metabolism, but result from disruption mass balance within central carbon Mechanistically, this leads simultaneous both pentose phosphate pathway tri-carboxylic acid cycle, as demonstrate based on quantitative model. findings define whereby one metabolic toxicity by simultaneously affecting activity multiple related pathways.
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