Function

Glucose 6-phosphate isomerase or Phosphoglucose isomerase (PGI) is a multifunctional enzyme. 

In glycolysis, the enzyme carries out the second step of the pathway.  It isomerizes glucose 6-phosphate, an aldose,  into fructose 6-phosphate, a ketose.  Thus, PGI is classified as an isomerase. 

Converting glucose 6-phosphate into fructose 6-phosphate occurs in three steps: opening the sugar ring, a base-catalyzed proton transfer, and ring closure.  The glucose pyranose ring is formed between by the connection of C1 to C5 and the fructose furanose ring is through C2 to C5.  The isomerization process initially breaks the C1 to C5 bond.  The opened sugar with an aldehyde group on C1 is converted into a ketose with the carbonyl group on C2.  The proposed catalytic mechanism is thought to form a cis-enediol intermediate.  In this mechanism, a proton is transferred from C2 to the oxygen of the aldehyde group on C1and a double bond is formed between C1 and C2 resulting in the cis-enediol formation.  A proton transfer from the hydroxyl group on C2 to C1 completes the ketose formation.  The last step is the arrangement of the fructose furanose ring by the connection of C2 to C5.  PGI isomerization requires 1.7 kj/mol to commence and the net free energy change is -2.5 kj/mol, meaning the conversion of glucose 6-phosphate to fructose 6-phosphate is thermodynamically favored.

During gluconeogenesis, which is the formation of glucose from noncarbohydrate sources, PGI carries out the reverse function.  Fructose 6-phosphate is converted into glucose 6-phosphate and as expected from the free energy change for the reverse, it requires an input of energy.

PGI is specifically inhibited by 6-phosphogluconic acid and erythrose 4-phosphate. Both are thought to be competitive inhibitors.

PGI monomers are almost structurally identical to autocrine motility factor (AMF) and neuorleukin (NLK) in mammals.  AMF is a type of cytokine that controls cell differentiation  and growth in embryogenesis, immunity and inflammation.  Acting in an autocrine or paracrine manner, AMF's effect are mediated through cell receptor signal transduction.  NLK is a neurotrophic growth factor involved in motor neuron regeneration in vivo.  It also influences B cell Ig synthesis and promotes the growth of central nervous system and peripheral nervous system neurons in vitro.  Recent studies postulate that the highly acidic region on the upper surface of the large domain and the extended loop are involved in the biologic activity of NLK.