Glucose-6-phosphate dehydrogenase

Glucose-6-phosphate dehydrogenase, NAD binding domain
glucose 6-phosphate dehydrogenase from leuconostoc mesenteroides
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

Glucose-6-phosphate dehydrogenase
PDB rendering based on 1qki.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1QKI, 2BH9, 2BHL
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 • glucose binding • protein homodimerization activity • NADP binding Cellular component • nucleus • cytoplasm • centrosome • cytosol • internal side of plasma membrane • intracellular membrane-bounded organelle Biological process • cytokine production • carbohydrate metabolic process • pentose-phosphate shunt • lipid metabolic process • cholesterol biosynthetic process • NADPH regeneration • glutathione metabolic process • pentose-phosphate shunt, oxidative branch • negative regulation of protein glutathionylation • response to organic cyclic compound • pentose biosynthetic process • response to food • cellular response to oxidative stress • erythrocyte maturation • small molecule metabolic process • response to ethanol • ribose phosphate biosynthetic process • glucose 6-phosphate metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
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 HG1497_PATCH: 153.74 – 153.76 Mb	Chr X: 74.41 – 74.43 Mb
PubMed search
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Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) (EC 1.1.1.49) is an 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 .

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]

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).^[3]

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.^[4]

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.^[5]

Cell growth and proliferation are affected by G6PD.^[6] G6PD inhibitors are under investigation to treat cancers and other conditions.^[3] DHEA is a G6PD inhibitor.^[6]

See also

• Glucose-6-phosphate dehydrogenase deficiency
• Genetic resistance to malaria

References

Further reading

External links

• - G6PD Deficiency Website
• ATSDR - G6PD Deficiency

v t e PDB gallery 1qki: X-RAY STRUCTURE OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE (VARIANT CANTON R459L) COMPLEXED WITH STRUCTURAL NADP+  2bh9: X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP  2bhl: X-RAY STRUCTURE OF HUMAN GLUCOSE-6-PHOSPHATE DEHYDROGENASE (DELETION VARIANT) COMPLEXED WITH GLUCOSE-6-PHOSPHATE