Glucose-6-phosphate isomerase

Bacterial phosphoglucose 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
CDD	cd05016
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Glucose-6-phosphate isomerase (GPI), alternatively known as phosphoglucose isomerase/phosphoglucoisomerase (PGI) or phosphohexose isomerase (PHI), is an enzyme ( EC 5.3.1.9) that in humans is encoded by the GPI gene on chromosome 19.^[4] 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

Functional GPI is a 64-kDa dimer composed of two identical monomers.[6]^[7] 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.^[6]

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.

It is hypothesized that serine phosphorylation of this protein induces a conformational change to its secretory form.[7]

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.^[10]

Isomerization of glucose

D-Glucose	Phosphoglucose isomerase		D-Fructose
	Phosphoglucose isomerase

α-D-Glucose 6-phosphate	Phosphoglucose isomerase		α-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.

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-

When going from fructose-6-phosphate toward glucose-6-phosphate, the result could be mannose-6-phosphate if carbon C2 is given the wrong chirality, but the enzyme does not permit that result except at a very low, non-physiological, rate.^[11]

Function

This gene belongs to the GPI family.^[5] The protein encoded by this gene is a dimeric enzyme that catalyzes the reversible isomerization of G6P and F6P.^[12][13] Since the reaction is reversible, its direction is determined by G6P and F6P concentrations.^[9]

glucose 6-phosphate ↔ fructose 6-phosphate

The protein has different functions inside and outside the cell. In the

A deficiency of GPI is responsible for 4% of the hemolytic anemias due to glycolytic enzyme deficiencies.^{[12][13][25][26]} Several cases of GPI deficiency have recently been identified.^[27]

Elevated serum GPI levels have been used as a prognostic

Human GPI is capable of inducing arthritis in mice with varied genetic backgrounds via intradermal injection.[29]^[30]

See also

• Fructose-1-phosphate-aldolase enzyme, which converts fructose to glucose

Interactions

GPI is known to

• AMFR,^[21][23] and
• HER2.^[23]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Glycolysis and Gluconeogenesis edit]]

Glycolysis and Gluconeogenesis edit

1. ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

References