The Metabolism of Glycogen in Animals: -Glycogen Breakdown Is Catalyzed by Glycogen Phosphorylase
In skeletal muscle and liver, the glucose units of the outer branches of glycogen enter the glycolytic pathway through the action of three enzymes: glycogen phos phorylase, glycogen debranching enzyme, and phosphoglucomutase. Glycogen phosphorylase catalyzes the reaction in which an (α1→4) glycosidic linkage between two glucose residues at a nonreducing end of glycogen undergoes attack by inorganic phosphate (Pi), removing the terminal glucose residue as -D-glucose 1-phosphate (Fig. 15–3). This phosphorolysis reaction is different from the hydrolysis of glycosidic bonds by amylase during intestinal degradation of dietary glycogen and starch. In phosphorolysis, some of the energy of the glycosidic bond is preserved in the formation of the phosphate ester, glucose 1-phosphate. Pyridoxal phosphate is an essential cofactor in the glycogen phosphorylase reaction; its phosphate group acts as a general acid catalyst, promoting attack by Pi on the glycosidic bond. (This is an unusual role for this cofactor; its more typical role is as a cofactor in amino acid metabolism; see Fig. 18–6.) Glycogen phosphorylase acts repetitively on the nonreducing ends of glycogen branches until it reaches a point four glucose residues away from an (α1→6) branch point (see Fig. 7–15), where its action stops. Further degradation by glycogen phosphorylase can occur only after the debranching enzyme, formally known as oligo (α1→6) to (α1→4) glucantrans ferase, catalyzes two successive reactions that transfer branches (Fig. 15–4). Once these branches are trans ferred and the glucosyl residue at C-6 is hydrolyzed, glycogen phosphorylase activity can continue.
FIGURE 15–3 Removal of a terminal glucose residue from the nonreducing end of a glycogen chain by glycogen phosphorylase. This process is repetitive; the enzyme removes successive glucose residues until it reaches the fourth glucose unit from a branch point (see Fig. 15–4).
FIGURE 15–4 Glycogen breakdown near an (α1→6) branch point. Following sequential removal of terminal glucose residues by glycogen phosphorylase (see Fig. 15–3), glucose residues near a branch are removed in a two-step process that requires a bifunctional “de branching enzyme.” First, the transferase activity of the enzyme shifts a block of three glucose residues from the branch to a nearby nonreducing end, to which they are reattached in (α1→4) linkage. The single glucose residue remaining at the branch point, in (α1→6) linkage, is then released as free glucose by the enzyme’s (α1→6) glucosidase activity. The glucose residues are shown in shorthand form, which omits the -H, -OH, and -CH2OH groups from the pyranose rings.
