| PATHWAY OF GLYCOGENOLYSIS IN LIVER
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As with most metabolic pathways, separate enzymes, sometimes in separate subcellular compartments, are required for the forward and reverse pathways. The pathway of glycogenolysis (Fig. 12.3B) begins with removal of the abundant, external α1→4 -linked glucose residues in glycogen. This is accomplished not by a hydrolase, but by glycogen phosphorylase, an enzyme that uses cytosolic phosphate and releases glucose from glycogen in the form of Glc-1-P, which is converted into Glc-6-P by phosphoglucomutase. In liver the glucose is released from Glc-6-P by glucose-6-phosphatase (Glc-6-Pase), and the glucose exits via the GLUT-2 transporter into blood. The rate-limiting, regulatory step in glycogenolysis is catalyzed by phosphorylase, the first enzyme in the pathway.
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Table 12-2.
Hormones involved in control of glycogenolysis. |
| Body_ID: None |
| Hormonal control of glycogenolysis |
| Body_ID: T012002.50 |
| Hormone | Source | Initiator | Effect on glycogenolysis |
| Body_ID: T012002.100 |
| glucagon | pancreatic α-cells | hypoglycemia | rapid activation |
| Body_ID: T012002.150 |
| epinephrine | adrenal medulla | acute stress, hypoglycemia | rapid activation |
| Body_ID: T012002.200 |
| cortisol | adrenal cortex | chronic stress | chronic activation |
| Body_ID: T012002.250 |
| insulin | pancreatic β-cells | hyperglycemia | inhibition |
| Body_ID: T012002.300 |
| Phosphorylase is specific for α1→4 glycosidic linkages; it cannot cleave α1→6 linkages. Further, this enzyme cannot approach the branching glucose residues efficiently. Thus, as shown in Figure 12.3B, phosphorylase cleaves the external glucose residues until the branches are three or four residues long, then debranching enzyme, which has both transglycosylase and glucosidase activity, moves a short segment of glucose residues bound to the α1→6 branch to the end of an
adjacent α1→4 chain, leaving a single glucose residue at the branch point. This glucose is then removed by the exo-1,6-glucosidase activity of branching enzyme, allowing glycogen phosphorylase to proceed with degradation of the α1→4 chain until another branch point is approached, setting the stage for a repeat of the transglycosylase and glucosidase reactions. About 90% of the glucose is released from glycogen as Glc-1-P, and the remainder, derived from the α1→6 branching residues, as free glucose.
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