Glucose-6-phosphate isomerase

2018-10-27T21:59:39Z

74.7.165.189:

{{Distinguish|D-xylose isomerase}}
{{enzyme
| Name = Glucose-6-phosphate isomerase
| EC_number = 5.3.1.9
| CAS_number = 9001-41-6
| IUBMB_EC_number = 5/3/1/9
| GO_code = 0004347
| image = 1hox.jpg
| width = 270
| caption = Glucose-6-phosphate isomerase dimer, Rabbit
}}
{{Infobox protein family
| Symbol = bact-PGI_C
| Name = Bacterial phosphoglucose isomerase C-terminal region
| image = PDB 1x9h EBI.jpg
| width =
| caption = crystal structure of phosphoglucose/phosphomannose isomerase from pyrobaculum aerophilum in complex with fructose 6-phosphate
| Pfam = PF10432
| Pfam_clan =
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD = cd05016
| InterPro = IPR019490
}}
{{Infobox protein family
| Symbol = PGI
| Name = Phosphoglucose isomeras
| Pfam = PF00342
| Pfam_clan =
| InterPro =
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1pgi
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD = cd05015
}}
{{Infobox_gene}}

'''Glucose-6-phosphate isomerase''' ('''GPI'''), alternatively known as '''phosphoglucose isomerase/phosphoglucoisomerase''' ('''PGI''') or '''phosphohexose isomerase''' ('''PHI'''), is an [[enzyme]] that in humans is encoded by the ''GPI'' [[gene]] on chromosome 19.<ref name="uniprot">{{cite web | title = UniProtKB: P06744 (G6PI_HUMAN)| url = https://www.uniprot.org/uniprot/P06744| accessdate = }}</ref>
This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the [[cytoplasm]], the gene product functions as a glycolytic enzyme (glucose-6-phosphate isomerase) that interconverts [[glucose-6-phosphate]] (G6P) and [[fructose-6-phosphate]] (F6P). Extracellularly, the encoded protein (also referred to as neuroleukin) functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces [[immunoglobulin]] secretion. The encoded protein is also referred to as autocrine motility factor (AMF) based on an additional function as a [[tumor]]-secreted [[cytokine]] and [[angiogenic]] factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia, and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. [[Alternative splicing]] results in multiple transcript variants. [provided by RefSeq, Jan 2014]<ref name="entrez">{{cite web | title = Entrez Gene: GPI glucose phosphate isomerase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2821| accessdate = }}</ref>

== Structure ==
Functional GPI is a 64-kDa dimer composed of two identical monomers.<ref name="pmid10653639" /><ref name=pmid11004567>{{cite journal |vauthors=Haga A, Niinaka Y, Raz A |title=Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein. |journal=Biochim. Biophys. Acta |volume=1480 |issue= 1–2 |pages= 235–44 |year= 2000 |pmid= 11004567 |doi= 10.1016/s0167-4838(00)00075-3}}</ref> The two monomers interact notably through the two protrusions in a hugging embrace. The active site of each monomer is formed by a cleft between the two domains and the dimer interface.<ref name="pmid10653639" />

GPI monomers are made of two domains, one made of two separate segments called the large domain and the other made of the segment in between called the small domain.<ref name="pmid10318897">{{cite journal |vauthors=Sun YJ, Chou CC, Chen WS, Wu RT, Meng M, Hsiao CD |title=The crystal structure of a multifunctional protein: phosphoglucose isomerase/autocrine motility factor/neuroleukin |journal=Proc Natl Acad Sci U S A |volume=96 |issue=10 |pages=5412–5417 |date=May 1999 |pmid=10318897 |pmc=21873 |doi=10.1073/pnas.96.10.5412}}</ref> The two domains are each αβα sandwiches, with the small domain containing a five-strand β-sheet surrounded by α-helices while the large domain has a six-stranded β-sheet.<ref name="pmid10653639">{{cite journal |vauthors=Jeffery CJ, Bahnson BJ, Chien W, Ringe D, Petsko GA |title=Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme that moonlights as neuroleukin, autocrine motility factor, and differentiation mediator |journal=Biochemistry |volume=39 |issue=5 |pages=955–64 |date=February 2000 |pmid=10653639 |doi=10.1021/bi991604m}}</ref> The large domain, located at the [[N-terminal]], and the [[C-terminal]] of each monomer also contain "arm-like" protrusions.<ref name="pmid10318897" /><ref name=pmid12573240>{{cite journal|last1=Cordeiro|first1=AT|last2=Godoi|first2=PH|last3=Silva|first3=CH|last4=Garratt|first4=RC|last5=Oliva|first5=G|last6=Thiemann|first6=OH|title=Crystal structure of human phosphoglucose isomerase and analysis of the initial catalytic steps.|journal=Biochimica et Biophysica Acta|date=21 February 2003|volume=1645|issue=2|pages=117–22|pmid=12573240|doi=10.1016/s1570-9639(02)00464-8}}</ref> Several [[amino acid|residues]] in the small domain serve to bind phosphate, while other residues, particularly His388, from the large and C-terminal domains are crucial to the sugar ring-opening step catalyzed by this enzyme. Since the isomerization activity occurs at the dimer interface, the dimer structure of this enzyme is critical to its catalytic function.<ref name=pmid12573240/>

It is hypothesized that serine phosphorylation of this protein induces a conformational change to its secretory form.<ref name=pmid11004567/>

== Mechanism ==
The mechanism that GPI uses to interconvert glucose 6-phosphate and fructose 6-phosphate (aldose to ketose) consists of three major steps: opening the glucose ring, isomerizing glucose into fructose through an enediol intermediate, and closing the fructose ring.<ref name="pmid11371164">{{cite journal |vauthors=Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C |title=The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia |journal=J Mol Biol |volume=309 |issue=2 |pages=447–63 |date=June 2001 |pmid=11371164 |doi=10.1006/jmbi.2001.4680 }}</ref>

=== Isomerization of glucose ===
{{Enzymatic Reaction
|forward_enzyme=[[Phosphoglucose isomerase]]
|reverse_enzyme=[[Phosphoglucose isomerase]]
|substrate=D-[[Glucose]]
|product=D-[[Fructose]]
|reaction_direction_(forward/reversible/reverse)=reversible
|minor_forward_substrate(s)=
|minor_forward_product(s)=
|minor_reverse_substrate(s)=
|minor_reverse_product(s)=
|substrate_image=D-glucose_wpmp.svg
|product_image=Alpha-d-fructose.svg
}}
{{Enzymatic Reaction
|forward_enzyme=[[Phosphoglucose isomerase]]
|reverse_enzyme=[[Phosphoglucose isomerase]]
|substrate=α-D-[[Glucose 6-phosphate]]
|product=β-D-[[Fructose 6-phosphate]]
|reaction_direction_(forward/reversible/reverse)=reversible
|minor_forward_substrate(s)=
|minor_forward_product(s)=
|minor_reverse_substrate(s)=
|minor_reverse_product(s)=
|substrate_image=Alpha-D-glucose-6-phosphate wpmp.png
|product_image=Beta-D-fructose-6-phosphate wpmp.png
}}
{{KEGG compound|C00668}} {{KEGG enzyme|5.3.1.9}} {{KEGG compound|C05345}} {{KEGG reaction|R00771}}

Glucose 6-phosphate binds to GPI in its pyranose form. The ring is opened in a "push-pull" mechanism by His388, which protonates the C5 oxygen, and Lys518, which deprotonates the C1 hydroxyl group. This creates an open chain aldose. Then, the substrate is rotated about the C3-C4 bond to position it for isomerization. At this point, Glu357 deprotonates C2 to create a ''cis''-enediolate intermediate stabilized by Arg272. To complete the isomerization, Glu357 donates its proton to C1, the C2 hydroxyl group loses its proton and the open-chain ketose fructose 6-phosphate is formed. Finally, the ring is closed by rotating the substrate about the C3-C4 bond again and deprotonating the C5 hydroxyl with Lys518.<ref name="pmid15342241">{{cite journal |vauthors=Graham Solomons JT, Zimmerly EM, Burns S, Krishnamurthy N, Swan MK, Krings S, Muirhead H, Chirgwin J, Davies C |title=The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening |journal=J Mol Biol |volume=342 |issue=3 |pages=847–60 |date=September 2004 |pmid=15342241 |doi=10.1016/j.jmb.2004.07.085}}</ref>

== Function ==

This gene belongs to the GPI family.<ref name="entrez"/> The protein encoded by this gene is a dimeric enzyme that catalyzes the reversible isomerization of G6P and F6P.<ref name="pmid10916680">{{cite journal |vauthors=Kugler W, Lakomek M | title = Glucose-6-phosphate isomerase deficiency | journal =Best Practice & Research Clinical Haematology | volume = 13 | issue = 1 | pages = 89–101 |date=March 2000 | pmid = 10916680 | doi = 10.1053/beha.1999.0059}}</ref><ref name=pmid21970785>{{cite journal|last1=Somarowthu|first1=S|last2=Brodkin|first2=HR|last3=D'Aquino|first3=JA|last4=Ringe|first4=D|last5=Ondrechen|first5=MJ|last6=Beuning|first6=PJ|title=A tale of two isomerases: compact versus extended active sites in ketosteroid isomerase and phosphoglucose isomerase.|journal=Biochemistry|date=1 November 2011|volume=50|issue=43|pages=9283–95|pmid=21970785|doi=10.1021/bi201089v}}</ref> Since the reaction is reversible, its direction is determined by G6P and F6P concentrations.<ref name=pmid12573240/>

[[glucose 6-phosphate]] <=> [[fructose 6-phosphate]]

The protein has different functions inside and outside the cell. In the [[cytoplasm]], the protein is involved in [[glycolysis]] and [[gluconeogenesis]], as well as the pentose phosphate pathway.<ref name=pmid12573240/> Outside the cell, it functions as a [[neurotrophic factor]] for spinal and sensory neurons, called '''neuroleukin'''.<ref name=pmid21970785/> The same protein is also secreted by [[cancer]] cells, where it is called '''autocrine motility factor'''<ref name="pmid17029220">{{cite journal |vauthors=Dobashi Y, Watanabe H, Sato Y, etal |title=Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas |journal=J. Pathol. |volume=210 |issue=4 |pages=431–40 |date=December 2006 |pmid=17029220 |doi=10.1002/path.2069}}</ref> and stimulates [[metastasis]].<ref>{{cite journal |vauthors=Watanabe H, Takehana K, Date M, Shinozaki T, Raz A |title=Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide |journal=Cancer Res. |volume=56 |issue=13 |pages=2960–3 |date=1 July 1996|pmid=8674049 |url=http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=8674049 }}</ref> Extracellular GPI is also known to function as a maturation factor.<ref name=pmid12573240/><ref name=pmid21970785/>

===Neuroleukin===

Though originally treated as separate proteins, cloning technology demonstrated that GPI is almost identical to the protein '''neuroleukin'''.<ref name="pmid3352744">{{cite journal |vauthors=Chaput M, Claes V, Portetelle D, Cludts I, Cravador A, Burny A, Gras H, Tartar A |title=The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase |journal=Nature |volume=332 |issue=6163 |pages=454–5 |date=March 1988 |pmid=3352744 |doi=10.1038/332454a0}}</ref> Neuroleukin is a [[neurotrophic factor]] for spinal and sensory neurons. It is found in large amounts in muscle, brain, heart, and kidneys.<ref name="pmid3764429">{{cite journal |vauthors=Gurney ME, Heinrich SP, Lee MR, Yin HS |title=Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons |journal=Science |volume=234 |issue=4776 |pages=566–74 |date=October 1986 |pmid=3764429 |doi=10.1126/science.3764429}}</ref> Neuroleukin also acts as a [[lymphokine]] secreted by T cells stimulated by lectin. It induces immunoglobulin secretion in [[B cells]] as part of a response that activates antibody-secreting cells.<ref name="pmid3020690">{{cite journal |vauthors=Gurney ME, Apatoff BR, Spear GT, Baumel MJ, Antel JP, Bania MB, Reder AT |title=Neuroleukin: a lymphokine product of lectin-stimulated T cells |journal=Science |volume=234 |issue=4776 |pages=574–81 |date=October 1986 |pmid=3020690 |doi=10.1126/science.3020690}}</ref>

===Autocrine motility factor===
Cloning experiments also revealed that GPI is identical to the protein known as '''autocrine motility factor''' (AMF).<ref name="pmid8674049">{{cite journal |vauthors=Watanabe H, Takehana K, Date M, Shinozaki T, Raz A |title=Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide | journal=Cancer Res. |volume=56 |issue=13 |pages=2960–3 |date=July 1996 |pmid=8674049 |url=http://cancerres.aacrjournals.org/content/56/13/2960.long}}</ref> AMF produced and secreted by cancer cells and stimulates cell growth and motility as a [[growth factor]].<ref name="pmid8392842">{{cite journal |vauthors=Silletti S, Raz A |title=Autocrine motility factor is a growth factor | journal=Biochem Biophys Res Commun |volume=194 |issue=1 |pages=454–5 |date=July 1993 |pmid=8392842 |doi=10.1006/bbrc.1993.1840}}</ref> AMF is thought to play a key role in cancer [[metastasis]] by activating the [[MAPK]]/[[Extracellular signal-regulated kinases|ERK]] or [[PI3K]]/[[AKT]] pathways.<ref name=pmid21252914/><ref name="pmid3085086">{{cite journal |vauthors=Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK, Schiffmann E |title=Tumor cell autocrine motility factor | journal=Proc Natl Acad Sci U S A |volume=83 |issue=10 |pages=3302–6 |date=May 1986 |pmid=3085086 |url=http://cancerres.aacrjournals.org/content/56/13/2960.long |doi=10.1073/pnas.83.10.3302 |pmc=323501}}</ref><ref name=pmid23248119>{{cite journal|last1=Kho|first1=DH|last2=Nangia-Makker|first2=P|last3=Balan|first3=V|last4=Hogan|first4=V|last5=Tait|first5=L|last6=Wang|first6=Y|last7=Raz|first7=A|title=Autocrine motility factor promotes HER2 cleavage and signaling in breast cancer cells.|journal=Cancer Research|date=15 February 2013|volume=73|issue=4|pages=1411–9|pmid=23248119|doi=10.1158/0008-5472.can-12-2149|pmc=3577983}}</ref> In the PI3K/AKT pathway, AMF interacts with gp78/[[AMFR]] to regulate [[endoplasmic reticulum|ER]] calcium release, and therefore protect against [[apoptosis]] in response to ER stress.<ref name=pmid21252914>{{cite journal|last1=Fu|first1=M|last2=Li|first2=L|last3=Albrecht|first3=T|last4=Johnson|first4=JD|last5=Kojic|first5=LD|last6=Nabi|first6=IR|title=Autocrine motility factor/phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release.|journal=Cell Death & Differentiation|date=June 2011|volume=18|issue=6|pages=1057–70|pmid=21252914|doi=10.1038/cdd.2010.181|pmc=3131941}}</ref>

==Prokaryotic bifunctional glucose-6-phosphate isomerase==

In some [[archaea]] and [[bacteria]] glucose-6-phosphate isomerase activity occurs via a bifunctional [[enzyme]] that also exhibits [[phosphomannose isomerase]] (PMI) activity. Though not closely related to [[eukaryotic]] GPIs, the bifunctional enzyme is similar enough that the [[sequence (biology)|sequence]] includes the cluster of [[threonine]]s and [[serine]]s that forms the sugar phosphate-binding site in conventional GPI. The enzyme is thought to use the same [[catalysis|catalytic mechanism]]s for both [[glucose]] ring-opening and [[isomerisation|isomerization]] for the interconversion of G6P to F6P.<ref name="pmid15252053">{{cite journal |vauthors=Swan MK, Hansen T, Schonheit P, Davies C | title = A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily: structural evidence at 1.16-A resolution | journal = J. Biol. Chem. | volume = 279 | issue = 38 | pages = 39838–45 |date=September 2004 | pmid = 15252053 | doi = 10.1074/jbc.M406855200 | url = }}</ref>

== Clinical significance ==

A deficiency of GPI is responsible for 4% of the [[hemolytic anemia]]s due to glycolytic enzyme deficiencies.<ref name="pmid10916680"/><ref name=pmid21970785/><ref name="pmid8499925">{{cite journal |vauthors=Walker JI, Layton DM, Bellingham AJ, Morgan MJ, Faik P | title = DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency | journal = Hum. Mol. Genet. | volume = 2 | issue = 3 | pages = 327–9 |date=March 1993 | pmid = 8499925 | doi = 10.1093/hmg/2.3.327 }}</ref><ref name="pmid8822954">{{cite journal |vauthors=Kanno H, Fujii H, Hirono A, Ishida Y, Ohga S, Fukumoto Y, Matsuzawa K, Ogawa S, Miwa S | title = Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia | journal = Blood | volume = 88 | issue = 6 | pages = 2321–5 |date=September 1996 | pmid = 8822954 | doi = | url = }}</ref> Several cases of GPI deficiency have recently been identified.<ref>{{cite web|title=GPI Deficiency|url=http://www.gpideficiency.org}}</ref>

Elevated serum GPI levels have been used as a prognostic [[biomarker]] for [[colorectal cancer|colorectal]], [[breast cancer|breast]], [[lung cancer|lung]], [[kidney cancer|kidney]], [[gastrointestinal cancer|gastrointestinal]], and other [[cancer]]s.<ref name=pmid11004567/><ref name=pmid21970785/> As AMF, GPI is attributed with regulating cell migration during invasion and [[metastasis]].<ref name=pmid11004567/> One study showed that the external layers of [[breast tumor]] spheroids (BTS) secrete GPI, which induces [[epithelial–mesenchymal transition]] (EMT), invasion, and metastasis in BTS. The GPI inhibitors ERI4P and 6PG were found to block metastasis of BTS but not BTS glycolysis or fibroblast viability. In addition, GPI is secreted exclusively by tumor cells and not normal cells. For these reasons, GPI inhibitors may be a safer, more targeted approach for anti-cancer therapy.<ref name=pmid24440856>{{cite journal|last1=Gallardo-Pérez|first1=JC|last2=Rivero-Segura|first2=NA|last3=Marín-Hernández|first3=A|last4=Moreno-Sánchez|first4=R|last5=Rodríguez-Enríquez|first5=S|title=GPI/AMF inhibition blocks the development of the metastatic phenotype of mature multi-cellular tumor spheroids.|journal=Biochimica et Biophysica Acta|date=June 2014|volume=1843|issue=6|pages=1043–53|pmid=24440856|doi=10.1016/j.bbamcr.2014.01.013}}</ref> GPI also participates in a [[positive feedback]] loop with [[HER2]], a major breast cancer therapeutic target, as GPI enhances HER2 expression and HER2 overexpression enhances GPI expression, and so on. As a result, GPI activity likely confers resistance in breast cancer cells against HER2-based therapies using [[Herceptin]]/Trastuzumab, and should be considered as an additional target when treating patients.<ref name=pmid23248119/>

==See also==
*[[Fructose-1-phosphate-aldolase]] enzyme, which converts fructose to glucose

==Interactions==
GPI is known to [[protein-protein interaction|interact]] with:
*[[AMFR]],<ref name=pmid21252914/><ref name=pmid23248119/> and
*[[HER2]].<ref name=pmid23248119/>

==Interactive pathway map==

{{GlycolysisGluconeogenesis_WP534|highlight=Glucose-6-phosphate_isomerase}}

==References==
{{Reflist}}

==Further reading==
{{Refbegin | 2}}
*{{cite journal |vauthors=Walker JI, Faik P, Morgan MJ |title=Characterization of the 5' end of the gene for human glucose phosphate isomerase (GPI). |journal=Genomics |volume=7 |issue= 4 |pages= 638–43 |year= 1990 |pmid= 2387591 |doi=10.1016/0888-7543(90)90212-D }}
*{{cite journal |vauthors=Brownstein BH, Silverman GA, Little RD, etal |title=Isolation of single-copy human genes from a library of yeast artificial chromosome clones. |journal=Science |volume=244 |issue= 4910 |pages= 1348–51 |year= 1989 |pmid= 2544027 |doi=10.1126/science.2544027 }}
*{{cite journal | author=Mizrachi Y |title=Neurotrophic activity of monomeric glucophosphoisomerase was blocked by human immunodeficiency virus (HIV-1) and peptides from HIV-1 envelope glycoprotein. |journal=J. Neurosci. Res. |volume=23 |issue= 2 |pages= 217–24 |year= 1989 |pmid= 2547084 |doi= 10.1002/jnr.490230212 }}
*{{cite journal |vauthors=Gurney ME, Apatoff BR, Spear GT, etal |title=Neuroleukin: a lymphokine product of lectin-stimulated T cells. |journal=Science |volume=234 |issue= 4776 |pages= 574–81 |year= 1986 |pmid= 3020690 |doi=10.1126/science.3020690 }}
*{{cite journal |vauthors=Faik P, Walker JI, Redmill AA, Morgan MJ |title=Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences. |journal=Nature |volume=332 |issue= 6163 |pages= 455–7 |year= 1988 |pmid= 3352745 |doi= 10.1038/332455a0 }}
*{{cite journal |vauthors=Zanella A, Izzo C, Rebulla P, etal |title=The first stable variant of erythrocyte glucose-phosphate isomerase associated with severe hemolytic anemia. |journal=Am. J. Hematol. |volume=9 |issue= 1 |pages= 1–11 |year= 1981 |pmid= 7435496 |doi=10.1002/ajh.2830090102 }}
*{{cite journal |vauthors=Faik P, Walker JI, Morgan MJ |title=Identification of a novel tandemly repeated sequence present in an intron of the glucose phosphate isomerase (GPI) gene in mouse and man. |journal=Genomics |volume=21 |issue= 1 |pages= 122–7 |year= 1994 |pmid= 7545951 |doi= 10.1006/geno.1994.1233 }}
*{{cite journal |vauthors=Xu W, Beutler E |title=The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia. |journal=J. Clin. Invest. |volume=94 |issue= 6 |pages= 2326–9 |year= 1995 |pmid= 7989588 |doi=10.1172/JCI117597 | pmc=330061 }}
*{{cite journal |vauthors=Xu W, Lee P, Beutler E |title=Human glucose phosphate isomerase: exon mapping and gene structure. |journal=Genomics |volume=29 |issue= 3 |pages= 732–9 |year= 1996 |pmid= 8575767 |doi= 10.1006/geno.1995.9944 }}
*{{cite journal |vauthors=Baronciani L, Zanella A, Bianchi P, etal |title=Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia. |journal=Blood |volume=88 |issue= 6 |pages= 2306–10 |year= 1996 |pmid= 8822952 |doi= }}
*{{cite journal |vauthors=Beutler E, West C, Britton HA, etal |title=Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA). |journal=Blood Cells Mol. Dis. |volume=23 |issue= 3 |pages= 402–9 |year= 1998 |pmid= 9446754 |doi= 10.1006/bcmd.1997.0157 }}
*{{cite journal |vauthors=Kanno H, Fujii H, Miwa S |title=Expression and enzymatic characterization of human glucose phosphate isomerase (GPI) variants accounting for GPI deficiency. |journal=Blood Cells Mol. Dis. |volume=24 |issue= 1 |pages= 54–61 |year= 1998 |pmid= 9616041 |doi= 10.1006/bcmd.1998.0170 }}
*{{cite journal |vauthors=Kugler W, Breme K, Laspe P, etal |title=Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency. |journal=Hum. Genet. |volume=103 |issue= 4 |pages= 450–4 |year= 1998 |pmid= 9856489 |doi=10.1007/s004390050849 }}
*{{cite journal |vauthors=Belyaeva OV, Balanovsky OP, Ashworth LK, etal |title=Fine mapping of a polymorphic CA repeat marker on human chromosome 19 and its use in population studies. |journal=Gene |volume=230 |issue= 2 |pages= 259–66 |year= 1999 |pmid= 10216265 |doi=10.1016/S0378-1119(99)00056-6 }}
*{{cite journal |vauthors=Yakirevich E, Naot Y |title=Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination. |journal=Biol. Reprod. |volume=62 |issue= 4 |pages= 1016–23 |year= 2000 |pmid= 10727272 |doi=10.1095/biolreprod62.4.1016 }}
*{{cite journal |vauthors=Haga A, Niinaka Y, Raz A |title=Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein. |journal=Biochim. Biophys. Acta |volume=1480 |issue= 1–2 |pages= 235–44 |year= 2000 |pmid= 11004567 |doi= 10.1016/s0167-4838(00)00075-3}}
{{Refend}}

==External links==
* [http://www.expasy.org/prosite/PDOC00157 Glucose-6-phosphate isomerase] in [[PROSITE]]
* [http://biology.kenyon.edu/BMB/Chime2/2001/phosphoglucose%20isomerase/FRAMES/text.htm Phosphoglucose Isomerase]
* [http://www.gpideficiency.org Glucose phosphate isomerase deficiency]

{{InterPro content|IPR019490}}
{{PDB Gallery|geneid=2821}}
{{glycolysis}}
{{Gluconeogenesis}}
{{Intramolecular oxidoreductases}}
{{Enzymes}}
{{Growth factor receptor modulators}}
{{Portal bar|Molecular and Cellular Biology|Mitochondria|Gene Wiki|border=no}}

[[Category:Protein domains]]
[[Category:EC 5.3.1]]
[[Category:Tumor markers]]

wikidoc - User contributions [en]

Glucose-6-phosphate isomerase