Phosphoglycerate Dehydrogenase (PHGDH)

Phosphoglycerate dehydrogenase (PHGDH) is involved in the early steps of L-serine synthesis in animal cells. L-Serine is a pivotal amino acid since it serves as a precursor to a large number of essential metabolites besides D-serine, a major agonist of the N-methyl-D-aspartate (NMDA) receptor. PHGDH is the first and only rate-limiting enzyme in the de novo serine biosynthetic pathway and catalyzes the oxidation of 3-PG derived from glycolysis to 3-phosphohydroxypyruvate (3-PHP). Mutations in PHGDH gene have been found in a family with congenital microcephaly, psychomotor retardation and other symptoms. An increase in PGDH levels, due to overexpression, is also associated with a wide array of cancers. In culture, PGDH is required for tumor cell proliferation, but extracellular L-serine is not able to support cell proliferation. This has led to the hypothesis that the pathway is performing some function related to tumor growth other than supplying L-serine.

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