Overview
This lecture covers glycogen metabolism, including glycogenesis, glycogenolysis, their regulation, and associated disorders, focusing on pathways, enzymes, and differences between liver and muscle.
Glycogenesis (Glycogen Synthesis)
- Glycogenesis is the synthesis of glycogen from glucose, occurring in the cytosol of liver and muscle cells.
- Glycogen is a homopolymer of glucose with α-1,4 glycosidic bonds (linear) and α-1,6 at branch points (branching).
- Steps: glucose → glucose 6-phosphate (via glucokinase) → glucose 1-phosphate (via mutase) → UDP-glucose (with UTP).
- UDP-glucose is the activated form used for glycogen synthesis.
- A glycogen primer or glycogenin protein is needed to start synthesis if no preexisting glycogen is present.
- Glycogen synthase adds glucose residues from UDP-glucose to the primer, elongating the chain.
- Once the chain reaches 11-12 glucose units, the branching enzyme transfers 6-8 residues, creating α-1,6 branches.
- Elongation and branching alternate until mature glycogen is formed.
- Glycogen synthase is most active in the dephosphorylated state.
Glycogenolysis (Glycogen Breakdown)
- Glycogenolysis is the breakdown of glycogen to produce glucose, happening in the cytosol of liver and muscle.
- In liver, glycogenolysis releases free glucose for blood; in muscle, it provides glucose 6-phosphate for energy.
- Glycogen phosphorylase, aided by pyridoxal phosphate (PLP), removes glucose units as glucose 1-phosphate until reaching limit dextrin (four glucose units near a branch).
- The debranching enzyme has transferase activity (moves trisaccharide units to linear chains) and glucosidase activity (removes remaining glucose at branch, releasing free glucose).
- The process continues with further phosphorylase action until glycogen is fully degraded.
- Glucose 1-phosphate is converted to glucose 6-phosphate; in liver, it is then converted to free glucose, but in muscle, it enters glycolysis.
Regulation of Glycogen Metabolism
- Insulin and glucagon regulate glycogen metabolism via phosphorylation and dephosphorylation of glycogen synthase (activation/inactivation states).
- Glycogen synthase is active when dephosphorylated; glycogen phosphorylase is active when phosphorylated.
Key Terms & Definitions
- Glycogenesis — synthesis of glycogen from glucose.
- Glycogenolysis — breakdown of glycogen to release glucose.
- Glycogenin — protein that acts as a primer for glycogen synthesis.
- Glycogen synthase — key enzyme for elongating glycogen chains.
- Branching enzyme — creates α-1,6 branches in glycogen.
- Glycogen phosphorylase — enzyme that removes glucose units from glycogen.
- Debranching enzyme — enzyme with transferase and glucosidase activities for branch removal.
- Limit dextrin — structure with four glucose units left at a branch point after phosphorylase action.
- UDP-glucose — activated glucose donor in glycogen synthesis.
Action Items / Next Steps
- Review the steps of glycogenesis and glycogenolysis.
- Familiarize yourself with key enzymes and their regulatory states.
- Prepare to study glycogen storage disorders in detail.