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. Activation of phosphofructokinase-1 and pyruvate kinase, both of which are enzymes involved in activation of the glycolytic pathway. 3. It acts as a coenzyme for phosphoglucomutase in glycolysis and gluconeogenesis. 4. It acts as a cofactor for phosphopentomutase, which produces D-ribose-5-phosphate. 5. acts as a phosphate donor molecule for unknown nonmetabolic effector proteins. 6. It increases in concentration during skeletal muscle contraction. 7. Its dephosphorylation yields glucose-6-phosphate, which is an important precursor molecule in glycolysis and the pentose phosphate pathway. 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. This reactant can also form D-glucose-6-phosphate, 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 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 and one of the products are intermediates in the 'payoff' phase of glycolysis. In other words, two molecules involved with glucose-1,6-bisphosphate synthase are able to be both created and recycled in the glycolytic pathway. 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, fructose-1,6-bisphosphate, 3-phosphoglycerate, citrate, lithium, phosphoenolpyruvate, and acetyl CoA. The inhibition of the enzyme by fructose-1,6-bisphosphate is most likely a feedback inhibition due to the product of the enzyme activation of PFK-1. When too much fructose-1,6-bisphosphate is produced, it inhibited the production of more PFK-1 activator. The enzyme is also inhibited by PEP, which is a reagent of pyruvate kinase. The product of glucose-1,6-bisphosphate synthase activates pyruvate kinase. Glucose-1,6-bisphosphate synthase appears to be activated by the presence of one of its substrates: 1,3-bisphosphoglycerate.
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 phosphoglucomutase. Both enzymes contain serine linked phosphates in their active sites, both have the same molecular weights, and both require a metal ion cofactor. Perhaps most importantly, both enzymes produce glucose-1,6-bisphosphate as either a product or an intermediate.
Relevant links
KEGG: starch and sucrose metabolism with glucose-1,6-bisphosphate synthase
http://www.genome.jp/dbget-bin/show_pathway?map00500+2.7.1.106 BRENDA enzyme database link for glucose-1,6-bisphosphate synthase
http://www.brenda.uni-koeln.de/php/result_flat.php4?ecno=2.7.1.106 Structure of phosphoglucomutase in the protein data bank
