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Glucose-6-phosphate dehydrogenase

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Title: Glucose-6-phosphate dehydrogenase  
Author: World Heritage Encyclopedia
Language: English
Subject: Oxidation response, List of EC numbers (EC 1), Ohno's law, Glycineamide ribonucleotide, Heinz body
Collection: Ec 1.1.1, Enzymes of Known Structure, Nadph-Dependent Enzymes
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Glucose-6-phosphate dehydrogenase

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
Glucose-6-phosphate dehydrogenase, C-terminal domain
Identifiers
Symbol G6PD_C
Pfam PF02781
PROSITE PDOC00067
SCOP 1dpg
SUPERFAMILY 1dpg


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+ \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 .

Contents

  • Species distribution 1
  • Regulation 2
  • Clinical significance 3
  • List of medicines which cause lysis in G6PD 4
  • See also 5
  • References 6
  • Further reading 7
  • External links 8

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]

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

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]

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]

List of medicines which cause lysis in G6PD

Note that this list doesn't contain all the medicines which cause hemolysis:

See also

References

  1. ^
  2. ^
  3. ^
  4. ^ a b
  5. ^
  6. ^
  7. ^
  8. ^ a b

Further reading

External links

  • - G6PD Deficiency Website
  • ATSDR - G6PD Deficiency
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