Glucose-1,6-bisphosphate synthase
Glucose-1,6-bisphosphate synthase is a type of enzyme called a phosphotransferase and is involved in mammalian starch and sucrose metabolism (KEGG, 2.7.1.106). It catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to glucose-1-phosphate, yielding 3-phosphoglycerate and glucose-1,6-bisphosphate. The enzyme requires a divalent metal ion cofactor. Zinc (Zn), Magnesium (Mg), Manganese (Mn), Calcium (Ca), Nickel (Ni), Copper (Cu), Cadmium (Cd) 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. 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. Activation of phosphofructokinase-1 (PFK-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 (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 (1,3-bisphosphoglycerate) and one of the products (3-phosphoglycerate) 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 (a product), citrate, lithium, phosphoenolpyruvate (PEP), 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 (glucose-1,6-bisphosphate) activation of PFK-1 (the enzyme which produces fructose-1,6-bisphosphate). 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 (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). 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 (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