Phosphoglycerate dehydrogenase (PHGDH) (PHGDH)

Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the de novo serine biosynthesis pathway, catalyzing the NAD+-dependent oxidation of 3-phosphoglycerate to 3-phosphohydroxypyruvate (PMID: 27245171). This metabolic step is crucial for diverting glycolytic intermediates toward the production of serine, which subsequently supports the synthesis of nucleotides, proteins, and glutathione, as well as the one-carbon cycle (PMID: 21822290). PHGDH is frequently overexpressed or amplified in several cancers, most notably triple-negative breast cancer and melanoma, where it promotes cell proliferation and survival under nutrient-deprived conditions (PMID: 21822292). While small molecule inhibitors like NCT-503 and CBR-5884 target the protein's enzymatic activity, the PHGDH mRNA itself is a target for knockdown strategies using RNA interference (RNAi) or antisense oligonucleotides to reduce protein expression in research and potential therapeutic contexts (PMID: 31110015). Therapeutic targeting must consider the essential role of PHGDH in the central nervous system, as loss-of-function mutations in the PHGDH gene lead to severe neurodevelopmental disorders such as Neu-Laxova syndrome (PMID: 15133002).

Other names

3-phosphoglycerate dehydrogenase3-PGDHPGDHSERAPhosphoglycerate dehydrogenase mRNA

Small molecule inhibition of enzyme activity; RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated degradation of mRNA.