Explain regulation of glycogen metabolism and influence of hormones.
Structure of Glycogen
Storage form of glucose:
Glycogen is a branched polymer of glucose.
Comprised of multiple -(D-glucose) units linked by α–(1,4) glycosidic bonds.
Branches formed every 12 or 14 glucose residues via α-(1,6) bonds.
Advantages of branching:
Increased packing of glucose units.
Prevention of crystallization.
Non-reducing ends exist on each branch; only one reducing end capped by glycogenin.
Glycogenesis (Synthesis of Glycogen)
Process Overview:
Anabolic pathway.
Converts α-D-glucose to glycogen, primarily stored in liver and skeletal muscle.
Roles:
Liver Glycogen: Maintains blood glucose during well-fed state; decreases in starvation.
Muscle Glycogen: Provides fuel for ATP synthesis during exertion.
Steps in Glycogenesis
Conversion of glucose 6-phosphate to glucose 1-phosphate by Phosphoglucomutase.
Synthesis of UDP-glucose using UDP-glucose pyrophosphorylase.
Initiating a primer using glycogenin.
Chain elongation through glycogen synthase.
Formation of branches via 4:6 transferase (branching enzyme).
Detailed Process of Glycogenesis
Step 1: Glucose 6-phosphate to Glucose 1-phosphate:
Interconverted by Phosphoglucomutase.
Step 2: UDP-glucose Synthesis:
UDP-glucose created from glucose 1-phosphate and UTP.
Step 3: Primer Synthesis:
Glycogenin acts as a primer, accepting glucose residues.
Step 4: Chain Elongation:
Glycogen synthase extends chains by linking glucose units via α-(1,4) bonds.
Step 5: Branching:
Enzyme transfers 5-8 residues from a non-reducing end to create branches via α-(1,6) linkages.
Glycogenolysis (Breakdown of Glycogen)
Definition: Breakdown of glycogen to release glucose 1-phosphate and α-D-glucose.
Economics of Glycogenolysis:
A catabolic pathway; different enzymes than in glycogenesis.
Not a direct reversal process.
Steps in Glycogenolysis
Shortening of chains by Glycogen phosphorylase.
Debranching (move 3 residues) via 4:4 transferase.
Debranching (remove 1 glucose) using 1:6 glucosidase.
Conversion of glucose 1-phosphate to glucose 6-phosphate via Phosphoglucomutase.
Detailed Process of Glycogenolysis
Step 1: Glycogen phosphorylase cleaves α-(1,4)-linkages to release glucose 1-phosphate, ceasing 4 residues from any branch point (limit dextrin).
Step 2: 4:4 transferase removes three glucosyl units for re-attachment.
Step 3: Amylo-α-(1,6) glucosidase removes one glucose residue attached by α-(1,6) bond.
Step 4: Conversion of glucose 1-phosphate to glucose 6-phosphate occurs in liver for blood glucose release; muscle cells utilize for energy via glycolysis.
Regulation of Glycogen Metabolism
Regulated tightly to maintain glucose levels:
In liver: Glycogenesis increases in fed state, glycogenolysis in fasting.
In muscle: Glycogenolysis accelerates during exercise, glycogenesis at rest.
Hormonal Regulation
Insulin promotes glycogenesis, opposing glucagon and epinephrine, which stimulate glycogenolysis.
Active forms:
Glycogen synthase a (active) / Glycogen synthase b (inactive).
Glycogen phosphorylase a (active) / Glycogen phosphorylase b (inactive).
Mechanisms of Hormonal Regulation
Insulin activates signaling pathways to increase glycogen synthesis.