Control variates: Difference between revisions

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{{enzyme
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| Name = Glucose-6-phosphate dehydrogenase
| EC_number = 1.1.1.49
| CAS_number = 9001-40-5
| IUBMB_EC_number = 1/1/1/49
| GO_code = 0004345
| image =
| width =
| caption =
}}
{{Infobox protein family
| Symbol = G6PD_N
| Name = Glucose-6-phosphate dehydrogenase, NAD binding domain
| image = PDB 1dpg EBI.jpg
| width =
| caption = glucose 6-phosphate dehydrogenase from leuconostoc mesenteroides
| Pfam = PF00479
| Pfam_clan = CL0063
| InterPro = IPR022674
| SMART =
| PROSITE = PDOC00067
| MEROPS =
| SCOP = 1dpg
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
{{Infobox protein family
| Symbol = G6PD_C
| Name = Glucose-6-phosphate dehydrogenase, C-terminal domain
| image =
| width =
| caption =
| Pfam = PF02781
| Pfam_clan = 
| InterPro =
| SMART =
| PROSITE = PDOC00067
| MEROPS =
| SCOP = 1dpg
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
{{PBB|geneid=2539}}
 
'''Glucose-6-phosphate dehydrogenase''' ('''G6PD''' or '''G6PDH''') ({{EC number|1.1.1.49}}) is an [[cytosolic]]  [[enzyme]] that [[catalysis|catalyzes]] the [[chemical reaction]]
: D-glucose 6-phosphate + NADP<sup>+</sup> <math>\rightleftharpoons</math> 6-phospho-D-glucono-1,5-lactone + NADPH + H<sup>+</sup>
 
This enzyme is in the [[pentose phosphate pathway]] (see image), a [[metabolic pathway]] that supplies reducing energy to cells (such as [[erythrocyte]]s) by maintaining the level of the [[co-enzyme]] [[nicotinamide adenine dinucleotide|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 [[oxidation|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.<ref name="isbn1-4160-3121-9">{{cite book | author = Aster J, Kumar V, Robbins SL, Abbas AK, Fausto N, Cotran RS | title = Robbins and Cotran pathologic basis of disease | publisher = Saunders/Elsevier | location = | year = 2010 | pages = Kindle Locations 33340–33341 | isbn = 1-4160-3121-9 | oclc = | doi = | accessdate = }}</ref>
 
It is notable in humans when there is a [[Glucose-6-phosphate dehydrogenase deficiency|genetic deficiency of G6PD]] which predisposes to non-immune {{SWL|target=hemolytic anemia|type=mutation_results_in}}.
 
== 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]].<ref name="pmid9480890">{{cite journal | author = Corpas FJ, Barroso JB, Sandalio LM, Distefano S, Palma JM, Lupiáñez JA, Del Río LA | title = A dehydrogenase-mediated recycling system of NADPH in plant peroxisomes | journal = Biochem. J. | volume = 330 ( Pt 2) | issue = Pt 2| pages = 777–84 |date=March 1998 | pmid = 9480890 | pmc = 1219205 | doi = }}</ref>
 
== Regulation ==
 
'''Glucose-6-phosphate dehydrogenase''' is stimulated by its substrate Glucose 6 Phosphate. The usual ratio of NADPH/NADP<sup>+</sup> 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<sup>+</sup>, thus stimulating '''G6PD''' to produce more NADPH.
 
G6PD converts [[glucose-6-phosphate]] into [[6-phosphoglucono-δ-lactone]] and is the [[Rate-determining_step|rate-limiting]] enzyme of the ''pentose phosphate pathway''.
 
G6PD is one of a number of [[glycolysis|glycolytic enzyme]]s activated by the [[transcription factor]] [[HIF1A|Hypoxia-inducible factor 1]] (HIF1).<ref name=CRJune2012/>
 
== Clinical significance ==
 
G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from [[missense mutation]]s, have been described with wide ranging levels of [[enzyme activity]] and associated clinical symptoms. Two transcript variants encoding different [[isoform]]s have been found for this gene.<ref>{{cite web | title = Entrez Gene: G6PD glucose-6-phosphate dehydrogenase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2539| accessdate = }}</ref>
 
[[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.<ref name="pmid18177777">{{cite journal | author = Cappellini MD, Fiorelli G | title = Glucose-6-phosphate dehydrogenase deficiency | journal = Lancet | volume = 371 | issue = 9606 | pages = 64–74 |date=January 2008 | pmid = 18177777 | doi = 10.1016/S0140-6736(08)60073-2 | url = }}</ref>
 
[[File:Pathology of G6PD deficiency.png|center|none|400px|]]
 
Cell growth and proliferation are affected by G6PD.<ref name="Tian_1998">{{cite journal | author = Tian WN, Braunstein LD, Pang J, Stuhlmeier KM, Xi QC, Tian X, Stanton RC | title = Importance of glucose-6-phosphate dehydrogenase activity for cell growth | journal = J. Biol. Chem. | volume = 273 | issue = 17 | pages = 10609–17 |date=April 1998 | pmid = 9553122 | doi = 10.1074/jbc.273.17.10609| url = }}</ref> G6PD inhibitors are under investigation to treat cancers and other conditions.<ref name="CRJune2012">{{cite web | url = http://www.onclive.com/publications/targeted-therapies/2012/June-2012/Cancer-Research-Moves-Beyond-the-Original-Hallmarks-of-Cancer | title = Cancer Research Moves Beyond the Original Hallmarks of Cancer | author = de Lartigue J | date = 2012-06-12 | publisher = OncLive }}</ref> [[DHEA]] is a G6PD inhibitor.<ref name="Tian_1998"/>
 
== See also ==
* [[Glucose-6-phosphate dehydrogenase deficiency]]
* [[Genetic resistance to malaria]]
 
== References ==
{{reflist|2}}
 
==Further reading==
{{refbegin | 2}}
*{{cite journal  | author=Vulliamy T, Beutler E, Luzzatto L |title=Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene |journal=Hum. Mutat. |volume=2 |issue= 3 |pages= 159–67 |year= 1993 |pmid= 8364584 |doi= 10.1002/humu.1380020302 }}
*{{cite journal  | author=Mason PJ |title=New insights into G6PD deficiency |journal=Br. J. Haematol. |volume=94 |issue= 4 |pages= 585–91 |year= 1996 |pmid= 8826878 |doi=  }}
*{{cite journal  | author=Wajcman H, Galactéros F |title=[Glucose 6-phosphate dehydrogenase deficiency: a protection against malaria and a risk for hemolytic accidents] |journal=C. R. Biol. |volume=327 |issue= 8 |pages= 711–20 |year= 2004 |pmid= 15506519 |doi=10.1016/j.crvi.2004.07.010  }}
{{refend}}
 
== External links ==
* [http://www.g6pddeficiency.org/index.php - G6PD Deficiency Website]
* [http://www.atsdr.cdc.gov/csem/nitrate/no3treatment_management.html#g6pd ATSDR - G6PD Deficiency]
 
{{PDB Gallery|geneid=2539}}
{{Alcohol oxidoreductases}}
{{Pentose phosphate pathway}}
 
[[Category:EC 1.1.1]]
[[Category:NADPH-dependent enzymes]]
[[Category:Enzymes of known structure]]

Latest revision as of 11:34, 5 May 2014

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