Serine synthesis through PHGDH coordinates nucleotide levels by maintaining central carbon metabolism

• DOI: 10.1038/s41467-018-07868-6
• Publication Date: 2018-12-17T16:32:41Z
• Authors: Michael A. Reid; Annamarie E. Allen; Shiyu Liu; Maria V. Liberti; Pei Liu; Xiaojing Liu; Ziwei Dai; Xia Gao; Qian Wang; Ying Liu; Luhua Lai; Jason W. Locasale
• Keywords: Metabolic pathway; Serine hydroxymethyltransferase

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.