Glucose-1,6-bisphosphate

This enzyme [EC 5A.22], also known as glucose phos-phomutase, catalyzes the interconversion of a-o-glucose 1-phosphate and a-o-glucose 6-phosphate. For this reaction to occur, a-D-glucose 1,6-bisphosphate must be present. This bisphosphate is an intermediate in the reaction, being formed by the transfer of a phosphate residue from the enzyme to the substrate. However, the dissociation of bisphosphate from the enzyme complex is much slower than the overall isomerization. 

This enzyme [EC 5.4.2.7], also known as phosphodeoxy-ribomutase, catalyzes the interconversion of D-ribose 1-phosphate and D-ribose 5-phosphate. This enzyme will also catalyze the interconversion of 2-deoxy-D-ribose 1-phosphate and 2-deoxy-D-ribose 5-phosphate. The bisphosphate compound is the cofactor thus, D-ribose 1,5-bisphosphate, 2-deoxy-D-ribose 1,5-bisphosphate, or even a-D-glucose 1,6-bisphosphate. 

The phosphoryl donor is glucose 1,6-bisphosphate, which is formed from glucose 1-phosphate and ATP in a reaction catalyzed by phosphoglucokinase. 

The second step in glycogenesis is conversion of glucose-6-phosphate to glucose-1-phosphate by phosphoglucomutase in a reaction similar to that catalyzed by phospho-glyceromutase. The phosphoryl group of the enzyme participates in this reversible reaction in which glucose-1,6-bisphosphate serves as an intermediate ... 

The enzyme s phosphoryl group is transferred to glucose-6-phosphate, forming glucose-1,6-bisphosphate. As glucose-l-phosphate forms, the phosphoryl group attached to C-6 is transferred to the enzyme s serine residue. 

The biosynthesis of glycogen occurs from glucose-6-phosphate. As indicated earlier, this is one of several alternative fates of glucose-6-phosphate in addition to glycolysis. Glucose-6-phosphate via phosphoglucomutase and glucose-1,6-bisphosphate can be reversibly... 

The PMM/PGM is activated by glucose 1,6-bisphosphate, and exhibits substrate inhibition in steady-state kinetic assays. The substrate inhibition can be relieved by increased concentrations of glucose 1,6-bisphosphate, which is, of course, the intermediate in the reaction with phosphoglucose. Presumably, mannose 1,6-bisphosphate activates PMM/PGM as well, but this has not been tested. The substrate inhibition and its relief by the intermediate provide strong evidence for the proposed chemical mechanism. The inhibition arises when the bisphosphorylated intermediate dissociates prematurely from the enzyme during the catalytic cycle, and substrate binding to the unphosphorylated enzyme creates a dead-end complex. 

Mg " <1, 4> (<1> activation of forward reaction, optimal concentration 1 mM, inhibition of reverse reaction, Mg " forms a complex with the product glucose-1,6-bisphosphate [1] <4> MgCh as cofactor, optimal concentration 10-15 mM [3]) [1, 3]... 

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