Glucose-1,6-bisphosphate synthase
Glucose-1,6-bisphosphate synthase | |||||||||
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ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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Glucose-1,6-bisphosphate synthase is a type of enzyme called a
(image courtesy of the BRENDA enzyme database)
The enzyme requires a divalent metal ion cofactor. Zinc (Zn2+), Magnesium (Mg2+), Manganese (Mn2+), Calcium (Ca2+), Nickel (Ni2+), Copper (Cu2+), Cadmium (Cd2+) are all proven effective cofactors in vitro. Additionally, the enzyme appears to function optimally in a pH range from 7.3–8.7 and at a temperature of 25 °C.[1]
Metabolic significance of the catalyzed reaction
The main product, glucose-1,6-bisphosphate, appears to have several functions:
1. Inhibition of hexokinase, an enzyme used in the first step of glycolysis.[2]
2. Activation of
3. It acts as a
4. It acts as a cofactor for phosphopentomutase, which produces D-
6. It increases in concentration during skeletal muscle contraction.[6]
7. Its dephosphorylation yields
Glucose-1,6-bisphosphate is most likely used in correlation with gluconeolysis. The product’s inhibition of hexokinase and activation of PFK-1 and pyruvate kinase is indicative of its role in glycolysis. Glucose-1,6-bisphosphate inhibit hexokinase stopping the production glucose-6-phosphate from D-glucose. Its activation of PFK-1 and pyruvate kinase shows that glycolysis still continues without the production of glucose-6-phosphate from D-glucose. This means that the glucose-6-phosphate needed for glycolysis most likely comes from gluconeolysis.
The reactant glucose-1-phosphate is produced by gluconeolysis.[7] This reactant can also form D-glucose-6-phosphate,[8] which is needed for glycolysis. It can therefore be inferred that it is possible when glucose-1-phosphate is produced, it makes glucose-1,6-bisphosphate (with glucose-1,6-bisophosphate synthase) and glucose-6-phosphate. The glucose-1,6-bisphosphate increase the activity of glycolysis, of which glucose-6-phosphate is a reagent.
In addition, one of the reactants (
The reactant glucose 1-phosphate is an important precursor molecule in many different pathways, including glycolysis, gluconeogenesis and the pentose phosphate pathway.
Regulation of the enzyme
Glucose-1,6-bisphosphate synthase is allosterically inhibited by inorganic phosphate,
The inhibition of the enzyme by fructose-1,6-bisphosphate is most likely a
The enzyme is also inhibited by PEP, which is a reagent of pyruvate kinase. The product of glucose-1,6-bisphosphate synthase (glucose-1,6-bisphosphate) activates pyruvate kinase.
Glucose-1,6-bisphosphate synthase appears to be activated by the presence of one of its substrates: 1,3-bisphosphoglycerate (glycerate-1,3-bisphosphate).[6]
Enzyme structure
No structure determination of glucose-1,6-bisphosphate synthase has been documented to date. Nevertheless, studies have shown that its structure appears to be markedly similar to a related enzyme called
Relevant links
KEGG: starch and sucrose metabolism with glucose-1,6-bisphosphate synthase (EC# 2.7.1.106)
http://www.genome.jp/dbget-bin/show_pathway?map00500+2.7.1.106
BRENDA enzyme database link for glucose-1,6-bisphosphate synthase (EC# 2.7.1.106)
http://www.brenda.uni-koeln.de/php/result_flat.php4?ecno=2.7.1.106
Structure of phosphoglucomutase in the protein data bank
http://www.rcsb.org/pdb/explore.do?structureId=1LXT