Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

glucose-6-phosphate isomerase By Reference

Phosphoglucose isomerase (EC:5.3.1.9) (PGI) [PMID:1593646] is a dimeric enzyme that catalyses the reversible isomerisation of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. The multifunctional protein, PGI, is also known as neuroleukin (a neurotrophic factor that mediates the differentiation of neurons), autocrine motility factor (a tumour-secreted cytokine that regulates cell motility), differentiation and maturation mediator and myofibril-bound serine proteinase inhibitor, and has different roles inside and outside the cell. In the cytoplasm, it catalyses the second step in glycolysis, while outside the cell it serves as a nerve growth factor and cytokine [PMID:10653639].




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Products

The proposed mechanism for sugar isomerisation involves several steps and is thought to occur via general acid/base catalysis. Since glucose 6-phosphate and fructose 6-phosphate exist predominantly in their cyclic forms, PGI is believed to catalyse first the opening of the hexose ring to yield the straight chain form of the substrates. Glucose 6-phosphate and fructose 6-phosphate then undergo isomerisation via formation of a cis-enediol intermediate with the double bond located between C-1 and C-2. The intermediate then undergoes a second keto-enol tautomerisation with reprotonation of the substrate occuring at C1. This is then followed by ring closure.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Gly	Q9N1E2	272	1dqr	271
Lys	Q9N1E2	211	1dqr	210
Glu	Q9N1E2	217	1dqr	216
Arg	Q9N1E2	273	1dqr	272
Glu	Q9N1E2	358	1dqr	357
Lys	Q9N1E2	519	1dqr	518
His	Q9N1E2	389	1dqr	388

Step Components

decyclisation, assisted keto-enol tautomerisation, intramolecular nucleophilic addition, proton transfer, intramolecular elimination, native state of enzyme regenerated, cyclisation, overall reactant used



Step 1.

Ring opening step. His388 abstracts a proton from substrate, breaking the C-O bond and forming the open sugar ring.



Step 2.

Glu357 abstracts a proton from the C2 position of the open chain form of the substrate, resulting in the cis-enediol(ate) intermediate. His398 is inferred to act as the general acid in this step due to its proximity.



Step 3.

The protonated Glu357 side chain then transfers the same proton to the C-1 position of the intermediate, yielding the open chain form of d-fructose-6-phosphate



Step 4.

Lys518 initiates the catalytic ring closure reaction to form the final product,



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

• Kinetic Parameters

  Organism	KM Value [mM]	Substrate	Comment
  Archaeoglobus fulgidus	0.02	D-fructose 6-phosphate	pH 7.4, 70°C, mutant enzyme E93D
  Thermococcus kodakarensis	2.27	D-fructose 6-phosphate	at pH 6.0 and 37°C
  Homo sapiens	2.7	D-glucose 6-phosphate	mutant enzyme H100L, at 21°C in 20 mM HEPES buffer (pH 7.5)
  Pyrococcus furiosus	3.58	L-talose	pH 7.0, 95°C
  Acetivibrio thermocellus	489	D-glucose 6-phosphate	free enzyme, in 100 mM HEPES, 10 mM Mg2+ and 0.5 mM Mn2+, pH 7.5, 37°C

• Temperature

  Organism	Temperature Range	Comment
  Oryctolagus cuniculus	30 - 60	30°C: about 45% of maximal activity of immobilized enzyme, about 35% of maximal activity of soluble enzyme, 60°C: about 60% of maximal activity of immobilized enzyme, about 65% of maximal activity of immobilized enzyme
  Pyrococcus furiosus	40 - 98	temperature profile, overview
  Acetivibrio thermocellus	50 - 70	free and immobilized enzymes retain about 90% of their maximum activity at 50°C and 70°C, but only about 40% of optimum activity is exhibited at 30°C
  Methanocaldococcus jannaschii	60 - 95	60°C: about 30% of maximal activity, 95°C: about 30% of maximal activity

• pH

  Organism	pH Range	Comment
  Methanocaldococcus jannaschii	5.3 - 7	50% of maximal activity at pH 6.3 and pH 7.0
  Pyrococcus furiosus	6 - 8	about 50% of maximal activity above pH 6.0 and below pH 8.0
  Oryctolagus cuniculus	6 - 10	pH 6.0: about 70% of maximal activity of soluble enzyme, about 30% of maximal activity of immobilized enzyme
  Pyrobaculum aerophilum	6.3 - 8.8	more than 50% of maximum activity in this range
  Acetivibrio thermocellus	7 - 9	free and immobilized enzymes have approximately 75% and 40% of their maximum activity at pH 7.0 and pH 9.0

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Associated Proteins

Citations

• High-resolution melting (HRM)-based detection of polymorphisms in the malic enzyme and glucose-6-phosphate isomerase genes for Leishmania infantum genotyping.
• Preparation of mesoporous silica nanocarriers targeting glucose-6-phosphate isomerase inhibition and application in the treatment of rheumatoid arthritis.
• Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage.
• Exploring the chondroprotective effect of Chaenomeles speciosa on Glucose-6-Phosphate Isomerase model mice using an integrated approach of network pharmacology and experimental validation.
• A Novel Glucose-6-Phosphate Isomerase Exists in Chicken Breast Meat: A Selenium-Containing Enzyme that Should Be Re-recognized Through New Eyes.
• Glucose 6 Phosphate Isomerase Deficiency, a Rare Hemolytic Anemia Misdiagnosed as Hereditary Spherocytosis.
• Case report: Glucose 6-phosphate-isomerase deficiency combine with avascular necrosis of bilateral femoral head.
• Hereditary nonspherocytic hemolytic anemia caused by glucose-6-phosphate isomerase (GPI) deficiency in a Chinese patient: a case report.
• The Metabolite Saccharopine Impairs Neuronal Development by Inhibiting the Neurotrophic Function of Glucose-6-Phosphate Isomerase.
• Elevated Serum Glucose-6-Phosphate Isomerase Level in Patients with Knee Osteoarthritis.
• Attenuation of Hemolysis Due to Glucose-6-Phosphate Isomerase Deficiency With Ketogenic Diet - A Case Report.