3-Phosphoglycerate dehydrogenase (PHGDH)

3-Phosphoglycerate dehydrogenase (PHGDH) is the first committed enzyme in the phosphorylated pathway of L-serine biosynthesis. It converts 3-phosphoglycerate into 3-phosphohydroxypyruvate using NAD+ as a cofactor. In humans, it is a tetramer composed of four identical subunits, with its activity tightly regulated by substrate and allosteric inhibition. PHGDH is essential in producing serine, a critical amino acid for cellular proliferation, nucleic acid synthesis, and neurological function. The enzyme's gene, PHGDH, is specifically necessary for nervous system serine supply because dietary serine does not cross the blood-brain barrier. PHGDH has emerged as a significant therapeutic target in oncology, where its overexpression enables cancer cells to sustain increased biosynthetic needs and resist treatment. Mutations in PHGDH cause severe congenital disorders due to impaired serine synthesis, most notably affecting neurological development and function. Recent research has emphasized the enzyme's potential as a drug target for several cancer subtypes, and efforts are underway to develop specific inhibitors.

Other names

phosphoglycerate dehydrogenase3-phosphoglyceric acid dehydrogenase3PHP reductasealphaKG reductasealpha-phosphoglycerate dehydrogenaseD-3-phosphoglycerate dehydrogenaseglycerate-1,3-phosphate dehydrogenaseglycerate 3-phosphate dehydrogenasePGDHphosphoglycerate oxidoreductasephosphoglyceric acid dehydrogenase

Inhibition of serine biosynthesis pathway; drugs inhibit PHGDH enzyme activity, leading to decreased production of serine, limiting cancer cell growth and proliferation.