| Glucose-6-phosphate dehydrogenase |
| Identifiers |
| EC number |
1.1.1.49 |
| CAS number |
9001-40-5 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
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| Glucose-6-phosphate dehydrogenase, NAD binding domain |
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glucose 6-phosphate dehydrogenase from leuconostoc mesenteroides
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| Identifiers |
| Symbol |
G6PD_N |
| Pfam |
PF00479 |
| Pfam clan |
CL0063 |
| InterPro |
IPR022674 |
| PROSITE |
PDOC00067 |
| SCOP |
1dpg |
| SUPERFAMILY |
1dpg |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
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| Glucose-6-phosphate dehydrogenase, C-terminal domain |
| Identifiers |
| Symbol |
G6PD_C |
| Pfam |
PF02781 |
| PROSITE |
PDOC00067 |
| SCOP |
1dpg |
| SUPERFAMILY |
1dpg |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
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| Glucose-6-phosphate dehydrogenase |
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PDB rendering based on 1qki.
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1QKI, 2BH9, 2BHL
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| Identifiers |
| Symbols |
G6PD ; G6PD1 |
| External IDs |
OMIM: 305900 MGI: 105979 HomoloGene: 37906 ChEMBL: 5347 GeneCards: G6PD Gene |
| EC number |
1.1.1.49 |
| Gene ontology |
| Molecular function |
• glucose-6-phosphate dehydrogenase activity
• protein binding
• glucose binding
• identical protein binding
• protein homodimerization activity
• NADP binding
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| Cellular component |
• nucleus
• cytoplasm
• centrosome
• microtubule organizing center
• cytosol
• cytoplasmic side of plasma membrane
• membrane
• intracellular membrane-bounded organelle
• extracellular exosome
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| Biological process |
• cytokine production
• carbohydrate metabolic process
• glucose metabolic process
• pentose-phosphate shunt
• transcription initiation from RNA polymerase II promoter
• lipid metabolic process
• cholesterol biosynthetic process
• NADP metabolic process
• NADPH regeneration
• glutathione metabolic process
• pentose-phosphate shunt, oxidative branch
• gene expression
• negative regulation of protein glutathionylation
• response to organic cyclic compound
• pentose biosynthetic process
• substantia nigra development
• response to food
• cellular response to oxidative stress
• erythrocyte maturation
• regulation of neuron apoptotic process
• small molecule metabolic process
• response to ethanol
• ribose phosphate biosynthetic process
• glucose 6-phosphate metabolic process
• oxidation-reduction process
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| Sources: Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| 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] |
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Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) (EC 1.1.1.49) is a cytosolic enzyme that catalyzes the chemical reaction
- D-glucose 6-phosphate + NADP+ 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 .
Contents
- 1 Species distribution
- 2 Regulation
- 3 Clinical significance
- 4 List of medicines which cause lysis in G6PD
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Species distribution
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] Among humans, G6PD is common in certain insular groups, such as Parsis.[3]
Regulation
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]
Clinical significance
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.[5]
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.[6]
Cell growth and proliferation are affected by G6PD.[7] G6PD inhibitors are under investigation to treat cancers and other conditions.[4] DHEA is a G6PD inhibitor.[7]
List of medicines which cause lysis in G6PD
Note that this list doesn't contain all the medicines which cause hemolysis:[citation needed]
- Antipyretics
- Acetamilide
- Acetophenetidin
- Antipyrine
- Aspirin
- Antimalarials
- Chloroquine
- Primaquine
- Pamaquine
- Quinocide
- Plasmoquine
- Sulfonamides
- Sulfamilamide
- SulfaCetamide
- Sulfapyridine
- Salicyayo sulfapyridine
- N2 acetyl sulfanilamide
- Nitrofurantoin
- Furaltadone
- Furazolidone
- Nitrofurazone
- Sulfuae
- Sulfoxone
- Thiazolsulfone
- Dapsone
- Dimercaprol
- Orianse
- Neo salvarsan
- Qulndene
See also
- Glucose-6-phosphate dehydrogenase deficiency
- Genetic resistance to malaria
References
- ^ 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.
- ^ Corpas FJ, Barroso JB, Sandalio LM, Distefano S, Palma JM, Lupiáñez JA, Del Río LA (March 1998). "A dehydrogenase-mediated recycling system of NADPH in plant peroxisomes". Biochem. J. 330 (Pt 2): 777–84. PMC 1219205. PMID 9480890.
- ^ "G6PD Enzyme Deficiency". Retrieved October 24, 2014.
- ^ a b de Lartigue J (2012-06-12). "Cancer Research Moves Beyond the Original Hallmarks of Cancer". OncLive.
- ^ "Entrez Gene: G6PD glucose-6-phosphate dehydrogenase".
- ^ Cappellini MD, Fiorelli G (January 2008). "Glucose-6-phosphate dehydrogenase deficiency". Lancet 371 (9606): 64–74. doi:10.1016/S0140-6736(08)60073-2. PMID 18177777.
- ^ a b Tian WN, Braunstein LD, Pang J, Stuhlmeier KM, Xi QC, Tian X, Stanton RC (April 1998). "Importance of glucose-6-phosphate dehydrogenase activity for cell growth". J. Biol. Chem. 273 (17): 10609–17. doi:10.1074/jbc.273.17.10609. PMID 9553122.
Further reading
- 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". Hum. Mutat. 2 (3): 159–67. doi:10.1002/humu.1380020302. PMID 8364584.
- Mason PJ (1996). "New insights into G6PD deficiency". Br. J. Haematol. 94 (4): 585–91. PMID 8826878.
- Wajcman H, Galactéros F (2004). "[Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents]". C. R. Biol. 327 (8): 711–20. doi:10.1016/j.crvi.2004.07.010. PMID 15506519.
External links
- - G6PD Deficiency Website
- ATSDR - G6PD Deficiency
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PDB gallery
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1qki: X-RAY STRUCTURE OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE (VARIANT CANTON R459L) COMPLEXED WITH STRUCTURAL NADP+
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2bh9: X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP
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2bhl: X-RAY STRUCTURE OF HUMAN GLUCOSE-6-PHOSPHATE DEHYDROGENASE (DELETION VARIANT) COMPLEXED WITH GLUCOSE-6-PHOSPHATE
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Oxidoreductases: alcohol oxidoreductases (EC 1.1)
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| 1.1.1: NAD/NADP acceptor |
- 3-hydroxyacyl-CoA dehydrogenase
- 3-hydroxybutyryl-CoA dehydrogenase
- Alcohol dehydrogenase
- Aldo-keto reductase
- 1A1
- 1B1
- 1B10
- 1C1
- 1C3
- 1C4
- 7A2
- Aldose reductase
- Beta-Ketoacyl ACP reductase
- Carbohydrate dehydrogenases
- Carnitine dehydrogenase
- D-malate dehydrogenase (decarboxylating)
- DXP reductoisomerase
- Glucose-6-phosphate dehydrogenase
- Glycerol-3-phosphate dehydrogenase
- HMG-CoA reductase
- IMP dehydrogenase
- Isocitrate dehydrogenase
- Lactate dehydrogenase
- L-threonine dehydrogenase
- L-xylulose reductase
- Malate dehydrogenase
- Malate dehydrogenase (decarboxylating)
- Malate dehydrogenase (NADP+)
- Malate dehydrogenase (oxaloacetate-decarboxylating)
- Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)
- Phosphogluconate dehydrogenase
- Sorbitol dehydrogenase
- Hydroxysteroid dehydrogenase: 3 Beta
- 11 Beta
- 17 Beta
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| 1.1.2: cytochrome acceptor |
- D-lactate dehydrogenase (cytochrome)
- D-lactate dehydrogenase (cytochrome c-553)
- Mannitol dehydrogenase (cytochrome)
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| 1.1.3: oxygen acceptor |
- Glucose oxidase
- L-gulonolactone oxidase
- Xanthine oxidase
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| 1.1.4: disulfide as acceptor |
- Vitamin K epoxide reductase
- Vitamin-K-epoxide reductase (warfarin-insensitive)
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| 1.1.5: quinone/similar acceptor |
- Malate dehydrogenase (quinone)
- Quinoprotein glucose dehydrogenase
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| 1.1.99: other acceptors |
- Choline dehydrogenase
- L2HGDH
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- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Metabolism: carbohydrate metabolism · pentose phosphate pathway enzymes
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| oxidative |
- Glucose-6-phosphate dehydrogenase
- 6-phosphogluconolactonase
- Phosphogluconate dehydrogenase
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| nonoxidative |
- Phosphopentose isomerase
- Phosphopentose epimerase
- Transketolase
- Transaldolase
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Index of inborn errors of metabolism
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| Description |
- Metabolism
- Enzymes and pathways: citric acid cycle
- pentose phosphate
- glycoproteins
- glycosaminoglycans
- phospholipid
- cholesterol and steroid
- sphingolipids
- eicosanoids
- amino acid
- urea cycle
- nucleotide
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| Disorders |
- Citric acid cycle and electron transport chain
- Glycoprotein
- Proteoglycan
- Fatty-acid
- Phospholipid
- Cholesterol and steroid
- Eicosanoid
- Amino acid
- Purine-pyrimidine
- Heme metabolism
- Symptoms and signs
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| Treatment |
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