PHGDH (PGDH)

PHGDH is a member of the D-isomer specific 2-hydroxyacid dehydrogenase family. This new family consists of D-isomer-stereospecific enzymes. The conserved residues in this family appear to be the residues involved in the substrate binding and the catalytic reaction, and thus to be targets for site-directed mutagenesis. A number of NAD-dependent 2-hydroxyacid dehydrogenases which seem to be specific for the D-isomer of their substrate have been shown to be functionally and structurally related. PHGDH catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the first and rate-limiting step in the phosphorylated pathway of serine biosynthesis, using NAD+/NADH as a cofactor. Overexpression of PHGDH may cause certain breast cancers. Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency which is characterized by congenital microcephaly, psychomotor retardation, and seizures.

PHGDH (PGDH) Related Areas

Enzyme>>Other>> PHGDH

PHGDH (PGDH) Alternative Names

RP4-683H9.1, 3-PGDH, 3PGDH, PDG, PGAD, PGD, PGDH, SERA, 3-phosphoglycerate dehydrogenase, D-3-phosphoglycerate dehydrogenase [Homo sapiens]

3-PGDH, 3PGDH, 4930479N23, A10, PGAD, PGD, PGDH, SERA, 3-phosphoglycerate dehyrogenase, D-3-phosphoglycerate dehydrogenase [Mus musculus]

Summaries for PHGDH (PGDH)

Entrez Gene summary for PHGDH (PGDH):

PHGDH gene encodes the enzyme which is involved in the early steps of L-serine synthesis in animal cells. L-serine is required for D-serine and other amino acid synthesis. The enzyme requires NAD/NADH as a cofactor and forms homotetramers for activity. Mutations in PHGDH gene have been found in a family with congenital microcephaly, psychomotor retardation and other symptoms. Multiple alternatively spliced transcript variants have been found, however the full-length nature of most are not known. [provided by RefSeq, Aug 2011]

OMIM - description for PHGDH (PGDH):

3-Phosphoglycerate dehydrogenase (PHGDH; ) catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the first and rate-limiting step in the phosphorylated pathway of serine biosynthesis, using NAD+/NADH as a cofactor.

Wikipedia summary for PHGDH (PGDH):

D-3-phosphoglycerate dehydrogenase is an enzyme that in humans is encoded by the PHGDH gene.
3-Phosphoglycerate dehydrogenase (PHGDH; ) catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the first and rate-limiting step in the phosphorylated pathway of serine biosynthesis, using NAD+/NADH as a cofactor. Certain breast cancers are dependent on the overexpression of PHGDH.

Human PHGDH (PGDH) Protein General Information

 

• Protein names: D-3-phosphoglycerate dehydrogenase
  Short name=3-PGDH
  Short name=PHGDH
• Sequence length: 533 AA.
• Pathway: Amino-acid biosynthesis; L-serine biosynthesis; L-serine from 3-phospho-D-glycerate: step 1/3.
• Sequence similarities: Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
• Induction: Induced by 17-beta-estradiol (estrogenic ligand) and 4-hydroxytamoxifen (agonist/antagonist ligand). Positively regulated by the transcription factors SP1 and NF-Y.
• Subunit structure: Homotetramer
• Kinetic parameters:
  K_M=21.6 µM for 3-phosphohydroxypyruvate
  V_max=35 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate (in patient-derived fibroblasts)
  V_max=168 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate (in 3-PGDH overexpressed cells)
• Catalytic activity: 3-phospho-D-glycerate + NAD⁺ = 3-phosphonooxypyruvate + NADH.
  2-hydroxyglutarate + NAD⁺ = 2-oxoglutarate + NADH.
• Involvement in disease: Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) . It is characterized by congenital microcephaly, psychomotor retardation, and seizures.

General information above from UniProt

Function for PHGDH (PGDH) Protein

Genatlas:

• PHGDH is involved in transition of phosphoglycerate to 3- phosphohydroxyglycerate, initiating and rate limiting step in the phosphorylated pathway of serine biosynthesis pathway
• PHGDH is necessary for serine biosynthesis, which serves as a substrate for protein synthesis
• PHGDH catalyzes the first step in L-serine synthesis via the phosphorylated pathway

Homology for human PHGDH (PGDH)

• homolog to rattus Phgdh (94.2 pc)
• homolog to murine Phdgh (94.6 pc)

Phenotype Information for PHGDH (PGDH)

• Gene/Locus: PHGDH
• Phenotype: Phosphoglycerate dehydrogenase deficiency

Phenotype Information for PHGDH (PGDH) from OMIM (Online Mendelian Inheritance in Man)