Phosphoglycerate dehydrogenase

Phosphoglycerate dehydrogenase

PDB rendering based on 2g76.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PHGDH ; 3-PGDH; 3PGDH; HEL-S-113; NLS; NLS1; PDG; PGAD; PGD; PGDH; PHGDHD; SERA
External IDs OMIM: 606879 MGI: 1355330 HomoloGene: 39318 GeneCards: PHGDH Gene
EC number 1.1.1.95
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 26227 236539
Ensembl ENSG00000092621 ENSMUSG00000053398
UniProt O43175 Q61753
RefSeq (mRNA) NM_006623 NM_016966
RefSeq (protein) NP_006614 NP_058662
Location (UCSC) Chr 1:
119.66 – 119.74 Mb		 Chr 3:
98.31 – 98.34 Mb
PubMed search
phosphoglycerate dehydrogenase
Identifiers
EC number 1.1.1.95
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

In enzymology, a D-3-phosphoglycerate dehydrogenase (EC 1.1.1.95) is an enzyme that catalyzes the chemical reactions

3-phospho-D-glycerate + NAD+ \rightleftharpoons 3-phosphonooxypyruvate + NADH + H+
2-hydroxyglutarate + NAD+ \rightleftharpoons 2-oxoglutarate + NADH + H+

Thus, in the first case, the two substrates of this enzyme are 3-phospho-D-glycerate and NAD+, whereas its 3 products are 3-phosphohydroxypyruvate, NADH, and H+; in the second case, the two substrates of this enzyme are 2-hydroxyglutarate and NAD+, whereas its 3 products are 2-oxoglutarate, NADH, and H+.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor.

In humans, this enzyme is encoded by the PHGDH gene.[1]

Function

3-Phosphoglycerate dehydrogenase (PHGDH; EC 1.1.1.95) 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.[1] Certain breast cancers are dependent on the overexpression of PHGDH.[2]

Clinical aspect

Homozygous or compound heterozygous mutations in PHGDH cause Neu-Laxova syndrome[3][4] and Phosphoglycerate dehydrogenase deficiency.[5]

References

  1. 1 2 "Entrez Gene: PHGDH phosphoglycerate dehydrogenase".
  2. ↑ Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, Kalaany NY, Hsu PP, Ottina K, Chan AM, Yuan B, Garraway LA, Root DE, Mino-Kenudson M, Brachtel EF, Driggers EM, Sabatini DM (Aug 2011). "Functional genomics reveal that the serine synthesis pathway is essential in breast cancer". Nature 476 (7360): 346–50. doi:10.1038/nature10350. PMC 3353325. PMID 21760589.
  3. ↑ Shaheen R, Rahbeeni Z, Alhashem A, Faqeih E, Zhao Q, Xiong Y, Almoisheer A, Al-Qattan SM, Almadani HA, Al-Onazi N, Al-Baqawi BS, Saleh MA, Alkuraya FS (Jun 2014). "Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH". American Journal of Human Genetics 94 (6): 898–904. doi:10.1016/j.ajhg.2014.04.015. PMID 24836451.
  4. ↑ Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, et al. (Sep 2014). "Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway". American Journal of Human Genetics 95 (3): 285–93. doi:10.1016/j.ajhg.2014.07.012. PMID 25152457.
  5. ↑ Jaeken J, Detheux M, Van Maldergem L, Foulon M, Carchon H, Van Schaftingen E (Jun 1996). "3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis". Archives of Disease in Childhood 74 (6): 542–5. doi:10.1136/adc.74.6.542. PMC 1511571. PMID 8758134.

Further reading

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