Overview
This lecture explains the process of glycogenesis, the synthesis of glycogen from glucose, highlighting key organs, steps, enzymes, and the formation of glycosidic bonds.
Key Organs and Glycogen Storage
- Glycogenesis mainly occurs in the liver (stores ~100g glycogen) and muscles (store ~300-400g glycogen).
- Glycogen metabolism in these organs regulates glucose storage and availability.
Triggers and Regulation
- Glycogenesis occurs during the fed (absorptive) state when blood glucose is high (post-meal, mild hyperglycemia).
- Insulin, a hormone from pancreatic beta cells, stimulates glycogenesis.
Glucose Uptake and Initial Steps
- Glucose enters liver cells via GLUT2 transporters; in muscle, via GLUT4.
- In the liver, glucose is phosphorylated by glucokinase (in muscle, by hexokinase) to form glucose 6-phosphate (G6P) using ATP.
Glucose Preparation for Glycogenesis
- Glucose 6-phosphate is converted to glucose 1-phosphate by the enzyme phosphoglucomutase (reversible reaction).
- Glucose 1-phosphate reacts with uridine triphosphate (UTP) to form UDP-glucose and pyrophosphate (PPi), catalyzed by UDP-glucose pyrophosphorylase.
- Pyrophosphate is rapidly hydrolyzed by pyrophosphatase, driving the reaction forward.
Glycogen Primer Formation
- UDP-glucose molecules are added to a protein called glycogenin, specifically to its tyrosine residues (autoglycosylation, no external enzyme needed initially).
- The first few glucose molecules are linked to glycogenin to form the primer.
Glycogen Chain Elongation and Branching
- Glycogen synthase adds more UDP-glucose units to the growing chain via α-1,4 glycosidic bonds.
- Branching enzyme (glycosyl (4→6) transferase) introduces α-1,6 glycosidic branches by transferring a chain segment to a different position.
- This branching increases solubility and storage capacity of glycogen.
Summary of Glycogen Structure
- Glycogen is a branched glucose polymer with α-1,4 and α-1,6 glycosidic bonds.
- The interplay between glycogen synthase (elongation) and branching enzyme (branch formation) builds the final glycogen molecule.
Key Terms & Definitions
- Glycogenesis — The process of synthesizing glycogen from glucose.
- Glycogenin — Protein primer for glycogen synthesis.
- UDP-glucose — Activated glucose donor for glycogen synthesis.
- Glycogen synthase — Enzyme catalyzing α-1,4 glycosidic bond formation.
- Branching enzyme — Enzyme creating α-1,6 glycosidic bonds in glycogen.
- α-1,4 glycosidic bond — Link between C1 of one glucose and C4 of another.
- α-1,6 glycosidic bond — Link between C1 of one glucose and C6 of another for branching.
Action Items / Next Steps
- Review the structure and function of key enzymes in glycogenesis.
- Prepare for the next lecture on glycogenolysis (glycogen breakdown).