Glycogen Debranching Enzyme - Function

Function

Together with phosphorylase, glycogen debranching enzymes function in glycogen breakdown and glucose mobilization. When phosphorylase has digested a glycogen branch down to four glucose residues, it will not remove further residues. Glycogen debranching enzymes assist phosphorylase, the primary enzyme involved in glycogen breakdown, mobilize glycogen stores. Phosphorylase can only cleave α-1,4- glycosidic bond between adjacent glucose molecules in glycogen but branches exist as α-1,6 linkages. When phosphorylase reaches four residues from a branching point it stops cleaving; because 1 in 10 residues is branched cleavage by phosphorylase alone would not be sufficient in mobilizing glycogen stores. Before phosphorylase can resume catabolism, debranching enzymes perform two functions:

• 4-α-D-glucanotransferase (EC 2.4.1.25), or glucosyltransferase, transfers three glucose residues from the four-residue glycogen branch to a nearby branch. This exposes a single glucose residue joined to the glucose chain though an α -1,6 glycosidic linkage

• Amylo-α-1,6-glucosidase (EC 3.2.1.33), or glucosidase, cleaves the remaining alpha-1,6 linkage, producing glucose and a linear chain of glycogen. The mechanism by which the glucosidase cleaves the α -1,6-linkage is not fully known because the amino acids in the active site have not yet been identified. It is thought to proceed through a two step acid base assistance type mechanism, with a oxocarbenium ion intermediate, and retention of configuration in glucose. This is a common method through which to cleave bonds, with an acid below the site of hydrolysis to lend a proton and a base above to deprotinate a water which can then act as a nucleophile. These acids and bases are amino acid side chains in the active site of the enzyme. A scheme for the mechanism is shown in the figure below.

Thus the debranching enzymes, transferase and α-1,6- glucosidase converts the branched glycogen structure into a linear one, paving the way for further cleavage by phosphorylase.