Enzyme - Glucose-6-phosphate isomerase

Alternative Name(s)
  • Hexosephosphate isomerase.
  • Phosphohexomutase.
  • Oxoisomerase.
  • Phosphohexose isomerase.
  • Phosphohexoisomerase.
  • Phosphoglucoisomerase.
  • Hexose monophosphate isomerase.
  • Phosphoglucose isomerase.
  • Phosphosaccharomutase.

Catalytic Activity

ldehydo-D-glucose 6-phosphate = keto-D-fructose 6-phosphate


There are no Cofactors for this Enzyme

Reaction Mechanism

    Phosphoglucose isomerase (EC: (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].

    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,


    The products of the reaction.

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

Associated Proteins

Protein name Organism
Glucose-6-phosphate isomerase 1 Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
Glucose-6-phosphate isomerase, cytosolic B Rice
Glucose-6-phosphate isomerase Human
Glucose-6-phosphate isomerase, cytosolic A Rice
Glucose-6-phosphate isomerase 1, chloroplastic Mouse-ear cress