Glucose-6-phosphate isomerase

Not to be confused with D-xylose isomerase.
Glucose-6-phosphate isomerase
Identifiers
EC number 5.3.1.9
CAS number 9001-41-6
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
Bacterial phospho-glucose isomerase C-terminal region
crystal structure of phosphoglucose/phosphomannose isomerase from pyrobaculum aerophilum in complex with fructose 6-phosphate
Identifiers
Symbol bact-PGI_C
Pfam PF10432
InterPro IPR019490
Phosphoglucose isomeras
Identifiers
Symbol PGI
Pfam PF00342
SCOP 1pgi
Glucose-6-phosphate isomerase

PDB rendering based on 1dqr.
Identifiers
Symbols GPI; AMF; DKFZp686C13233; GNPI; NLK; PGI; PHI; SA-36; SA36
External IDs OMIM: 172400 MGI: 95797 HomoloGene: 145 GeneCards: GPI Gene
EC number 5.3.1.9
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 2821 14751
Ensembl ENSG00000105220 ENSMUSG00000036427
UniProt P06744 n/a
RefSeq (mRNA) NM_000175.3 NM_008155.3
RefSeq (protein) NP_000166.2 NP_032181.2
Location (UCSC) Chr 19:
34.86 – 34.89 Mb		 Chr 7:
34.99 – 35.02 Mb
PubMed search [1] [2]

Glucose-6-phosphate isomerase, (alternatively known as phosphoglucose isomerase or phosphohexose isomerase), is an enzyme that catalyzes the conversion of glucose-6-phosphate into fructose 6-phosphate in the second step of glycolysis.

The human variant of this enzyme is encoded by the GPI gene.[1]

Contents

Function

This gene belongs to the GPI family whose members encode multifunctional phosphoglucose isomerase proteins involved in energy pathways. The protein encoded by this gene is a dimeric enzyme that catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate.

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, while outside the cell it functions as a neurotrophic factor for spinal and sensory neurons. The same protein is also secreted by cancer cells, where it is called autocrine motility factor[2] and stimulates metastasis.[3] 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.[1]

In glycolysis

α-D-Glucose 6-phosphate Phosphoglucose isomerase β-D-Fructose 6-phosphate
 
 
  Phosphoglucose isomerase

Compound C00668 at KEGG Pathway Database. Enzyme 5.3.1.9 at KEGG Pathway Database. Compound C05345 at KEGG Pathway Database. Reaction R00771 at KEGG Pathway Database.

As a glucose isomerase

D-Glucose Phosphoglucose isomerase D-Fructose
 
 
  Phosphoglucose isomerase

Other functions

There is evidence that phosphoglucose isomerase acts as a molecular messenger. It is produced and secreted by white blood cells, and acts to regulate the growth of several different cell types.

Pathology

A deficiency of phosphoglucose isomerase is responsible for 4% of the hemolytic anemias due to glycolytic enzyme deficiencies.

Prokaryotic bifunctional glucose-6-phosphate isomerase

In some archaea and bacteria glucose-6-phosphate isomerase (PGI) activity occurs via a bifunctional enzyme that also exhibits phosphomannose isomerase (PMI) activity. Though not closely related to eukaryotic PGIs, the bifunctional enzyme is similar enough that the sequence includes the cluster of threonines and serines that forms the sugar phosphate-binding site in conventional PGI. The enzyme is thought to use the same catalytic mechanisms for both glucose ring-opening and isomerisation for the interconversion of glucose 6-phosphate to fructose 6-phosphate.[4]

References

  1. ^ a b "Entrez Gene: GPI glucose phosphate isomerase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2821. 
  2. ^ Dobashi Y, Watanabe H, Sato Y, et al. (December 2006). "Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas". J. Pathol. 210 (4): 431–40. doi:10.1002/path.2069. PMID 17029220. 
  3. ^ Watanabe H, Takehana K, Date M, Shinozaki T, Raz A (1 July 1996). "Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide". Cancer Res. 56 (13): 2960–3. PMID 8674049. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=8674049. 
  4. ^ Swan MK, Hansen T, Schonheit P, Davies C (September 2004). "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". J. Biol. Chem. 279 (38): 39838–45. doi:10.1074/jbc.M406855200. PMID 15252053. 

Further reading

  • Kugler W, Lakomek M (2000). "Glucose-6-phosphate isomerase deficiency.". Baillieres Best Pract. Res. Clin. Haematol. 13 (1): 89–101. PMID 10916680. 
  • Walker JI, Faik P, Morgan MJ (1990). "Characterization of the 5' end of the gene for human glucose phosphate isomerase (GPI).". Genomics 7 (4): 638–43. doi:10.1016/0888-7543(90)90212-D. PMID 2387591. 
  • Brownstein BH, Silverman GA, Little RD, et al. (1989). "Isolation of single-copy human genes from a library of yeast artificial chromosome clones.". Science 244 (4910): 1348–51. doi:10.1126/science.2544027. PMID 2544027. 
  • Mizrachi Y (1989). "Neurotrophic activity of monomeric glucophosphoisomerase was blocked by human immunodeficiency virus (HIV-1) and peptides from HIV-1 envelope glycoprotein.". J. Neurosci. Res. 23 (2): 217–24. doi:10.1002/jnr.490230212. PMID 2547084. 
  • Gurney ME, Apatoff BR, Spear GT, et al. (1986). "Neuroleukin: a lymphokine product of lectin-stimulated T cells.". Science 234 (4776): 574–81. doi:10.1126/science.3020690. PMID 3020690. 
  • Faik P, Walker JI, Redmill AA, Morgan MJ (1988). "Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences.". Nature 332 (6163): 455–7. doi:10.1038/332455a0. PMID 3352745. 
  • Zanella A, Izzo C, Rebulla P, et al. (1981). "The first stable variant of erythrocyte glucose-phosphate isomerase associated with severe hemolytic anemia.". Am. J. Hematol. 9 (1): 1–11. doi:10.1002/ajh.2830090102. PMID 7435496. 
  • Faik P, Walker JI, Morgan MJ (1994). "Identification of a novel tandemly repeated sequence present in an intron of the glucose phosphate isomerase (GPI) gene in mouse and man.". Genomics 21 (1): 122–7. doi:10.1006/geno.1994.1233. PMID 7545951. 
  • Xu W, Beutler E (1995). "The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia.". J. Clin. Invest. 94 (6): 2326–9. doi:10.1172/JCI117597. PMC 330061. PMID 7989588. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=330061. 
  • Walker JI, Layton DM, Bellingham AJ, et al. (1993). "DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency.". Hum. Mol. Genet. 2 (3): 327–9. doi:10.1093/hmg/2.3.327. PMID 8499925. 
  • Xu W, Lee P, Beutler E (1996). "Human glucose phosphate isomerase: exon mapping and gene structure.". Genomics 29 (3): 732–9. doi:10.1006/geno.1995.9944. PMID 8575767. 
  • Baronciani L, Zanella A, Bianchi P, et al. (1996). "Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia.". Blood 88 (6): 2306–10. PMID 8822952. 
  • Kanno H, Fujii H, Hirono A, et al. (1996). "Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia.". Blood 88 (6): 2321–5. PMID 8822954. 
  • Beutler E, West C, Britton HA, et al. (1998). "Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA).". Blood Cells Mol. Dis. 23 (3): 402–9. doi:10.1006/bcmd.1997.0157. PMID 9446754. 
  • Kanno H, Fujii H, Miwa S (1998). "Expression and enzymatic characterization of human glucose phosphate isomerase (GPI) variants accounting for GPI deficiency.". Blood Cells Mol. Dis. 24 (1): 54–61. doi:10.1006/bcmd.1998.0170. PMID 9616041. 
  • Kugler W, Breme K, Laspe P, et al. (1998). "Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency.". Hum. Genet. 103 (4): 450–4. doi:10.1007/s004390050849. PMID 9856489. 
  • Belyaeva OV, Balanovsky OP, Ashworth LK, et al. (1999). "Fine mapping of a polymorphic CA repeat marker on human chromosome 19 and its use in population studies.". Gene 230 (2): 259–66. doi:10.1016/S0378-1119(99)00056-6. PMID 10216265. 
  • Yakirevich E, Naot Y (2000). "Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination.". Biol. Reprod. 62 (4): 1016–23. doi:10.1095/biolreprod62.4.1016. PMID 10727272. 
  • Haga A, Niinaka Y, Raz A (2000). "Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein.". Biochim. Biophys. Acta 1480 (1-2): 235–44. PMID 11004567. 

External links

Glucose Hexokinase Glucose 6-phosphate Glucose-6-phosphate isomerase Fructose 6-phosphate phosphofructokinase-1 Fructose 1,6-bisphosphate Fructose bisphosphate aldolase
ATP ADP ATP ADP
Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Triosephosphate isomerase Glyceraldehyde 3-phosphate Glyceraldehyde-3-phosphate dehydrogenase 1,3-Bisphosphoglycerate
NAD+ + Pi NADH + H+
+ 2 2
Phosphoglycerate kinase 3-Phosphoglycerate Phosphoglycerate mutase 2-Phosphoglycerate Phosphopyruvate hydratase(Enolase) Phosphoenolpyruvate Pyruvate kinase Pyruvate
ADP ATP H2O ADP ATP
2 2 2 2

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
Glycolysis
Gluconeogenesis only
Regulatory

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
Isomerases: intramolecular oxidoreductases (EC 5.3)
5.3.1: Aldoses/Ketoses
5.3.2: Keto/Enol
5.3.3: C=C
5.3.4: S-S
5.3.99: other
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

This article incorporates text from the public domain Pfam and InterPro IPR019490