Glucose-6-phosphate dehydrogenase

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Glucose-6-phosphate dehydrogenase
EC number
CAS number 9001-40-5
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Glucose-6-phosphate dehydrogenase, NAD binding domain
PDB 1dpg EBI.jpg
glucose 6-phosphate dehydrogenase from leuconostoc mesenteroides
Symbol G6PD_N
Pfam PF00479
Pfam clan CL0063
InterPro IPR022674
SCOP 1dpg
Glucose-6-phosphate dehydrogenase, C-terminal domain
Symbol G6PD_C
Pfam PF02781
SCOP 1dpg
Glucose-6-phosphate dehydrogenase
Protein G6PD PDB 1qki.png
PDB rendering based on 1qki.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols G6PD ; G6PD1
External IDs OMIM305900 MGI105979 HomoloGene37906 ChEMBL: 5347 GeneCards: G6PD Gene
EC number
RNA expression pattern
PBB GE G6PD 202275 at tn.png
More reference expression data
Species Human Mouse
Entrez 2539 14381
Ensembl ENSG00000160211 ENSMUSG00000031400
UniProt P11413 Q00612
RefSeq (mRNA) NM_000402 NM_008062
RefSeq (protein) NP_000393 NP_032088
Location (UCSC) Chr X:
154.53 – 154.55 Mb
Chr X:
74.41 – 74.43 Mb
PubMed search [1] [2]

Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) (EC is a cytosolic enzyme that catalyzes the chemical reaction

D-glucose 6-phosphate + NADP+ \rightleftharpoons 6-phospho-D-glucono-1,5-lactone + NADPH + H+

This enzyme is in the pentose phosphate pathway (see image), a metabolic pathway that supplies reducing energy to cells (such as erythrocytes) by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage. Of greater quantitative importance is the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids, such as the liver, mammary glands, adipose tissue, and the adrenal glands. G6PD reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH while oxidizing glucose-6-phosphate.[1]

It is notable in humans when there is a genetic deficiency of G6PD which predisposes to non-immune hemolytic anemia .

Species distribution[edit]

G6PD is widely distributed in many species from bacteria to humans. In higher plants, several isoforms of G6PDH have been reported, which are localized in the cytosol, the plastidic stroma, and peroxisomes.[2] Humans have two isoforms of a single gene coding for G6PD.[3]


Glucose-6-phosphate dehydrogenase is stimulated by its substrate Glucose 6 Phosphate. The usual ratio of NADPH/NADP+ in the cytosol of tissues engaged in biosyntheses is about 100/1. Increased utilization of NADPH for fatty acid biosynthesis will dramatically increase the level of NADP+, thus stimulating G6PD to produce more NADPH.

G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the pentose phosphate pathway.

G6PD is one of a number of glycolytic enzymes activated by the transcription factor Hypoxia-inducible factor 1 (HIF1).[4]

G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates pentose phosphate pathway to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes.[5]

Clinical significance[edit]

G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. Two transcript variants encoding different isoforms have been found for this gene.[6]

Glucose-6-phosphate dehydrogenase deficiency is very common worldwide, and causes acute hemolytic anemia in the presence of simple infection, ingestion of fava beans, or reaction with certain medicines, antibiotics, antipyretics, and antimalarials.[7]

Pathology of G6PD deficiency.png

Cell growth and proliferation are affected by G6PD.[8] G6PD inhibitors are under investigation to treat cancers and other conditions.[4] DHEA is a G6PD inhibitor.[8]

See also[edit]


  1. ^ Aster J, Kumar V, Robbins SL, Abbas AK, Fausto N, Cotran RS (2010). Robbins and Cotran Pathologic Basis of Disease. Saunders/Elsevier. pp. Kindle Locations 33340–33341. ISBN 1-4160-3121-9. 
  2. ^ Corpas FJ, Barroso JB, Sandalio LM, Distefano S, Palma JM, Lupiáñez JA, Del Río LA (Mar 1998). "A dehydrogenase-mediated recycling system of NADPH in plant peroxisomes". The Biochemical Journal 330 (Pt 2): 777–84. doi:10.1042/bj3300777. PMC 1219205. PMID 9480890. 
  3. ^ "G6PD glucose-6-phosphate dehydrogenase [ Homo sapiens (human) ]". NCBI. Retrieved 13 December 2015. 
  4. ^ a b de Lartigue J (2012-06-12). "Cancer Research Moves Beyond the Original Hallmarks of Cancer". OncLive. 
  5. ^ Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, Xiong Y, Guan KL, Ye D (Jun 2014). "Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress". The EMBO Journal 33 (12): 1304–20. doi:10.1002/embj.201387224. PMID 24769394. 
  6. ^ "Entrez Gene: G6PD glucose-6-phosphate dehydrogenase". 
  7. ^ Cappellini MD, Fiorelli G (Jan 2008). "Glucose-6-phosphate dehydrogenase deficiency". Lancet 371 (9606): 64–74. doi:10.1016/S0140-6736(08)60073-2. PMID 18177777. 
  8. ^ a b Tian WN, Braunstein LD, Pang J, Stuhlmeier KM, Xi QC, Tian X, Stanton RC (Apr 1998). "Importance of glucose-6-phosphate dehydrogenase activity for cell growth". The Journal of Biological Chemistry 273 (17): 10609–17. doi:10.1074/jbc.273.17.10609. PMID 9553122. 

Further reading[edit]

  • Vulliamy T, Beutler E, Luzzatto L (1993). "Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene". Human Mutation 2 (3): 159–67. doi:10.1002/humu.1380020302. PMID 8364584. 
  • Mason PJ (Sep 1996). "New insights into G6PD deficiency". British Journal of Haematology 94 (4): 585–91. PMID 8826878. 
  • Wajcman H, Galactéros F (Aug 2004). "[Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents]". Comptes Rendus Biologies (in French) 327 (8): 711–20. doi:10.1016/j.crvi.2004.07.010. PMID 15506519. 

External links[edit]