Glycogenesis and Glycogenolysis
High-Yield Summary
- The pyruvate dehydrogenase complex irreversibly converts pyruvate → acetyl-CoA + NADH + CO2 in the mitochondrial matrix; stimulated by insulin, inhibited by acetyl-CoA. Acetyl-CoA then enters the citric acid cycle or is diverted to fatty acid synthesis.
- Glycogenesis (liver, muscle): glucose-6-P → glucose-1-P → UDP-glucose (activated form) → glycogen synthase adds alpha-1,4 bonds to the chain → branching enzyme adds alpha-1,6 branch points.
- Glycogenolysis: glycogen phosphorylase (rate-limiting) cleaves alpha-1,4 bonds, releasing glucose-1-phosphate (NOT free glucose); debranching enzyme handles alpha-1,6 branch points (transferase activity + alpha-1,6-glucosidase activity, releasing a small amount of free glucose).
- Released glucose-6-phosphate: in muscle → glycolysis for local ATP; in liver → dephosphorylated and released into blood (liver has glucose-6-phosphatase, muscle does not).
Key Terms
- UDP-glucose
- Activated form of glucose used by glycogen synthase to extend the glycogen chain.
- Glycogen synthase
- Rate-limiting enzyme of glycogenesis; forms alpha-1,4 glycosidic bonds.
- Glycogen phosphorylase
- Rate-limiting enzyme of glycogenolysis; cleaves alpha-1,4 bonds, releasing glucose-1-phosphate.
- Debranching enzyme
- Has transferase activity (moves glucose residues to expose a branch point) and alpha-1,6-glucosidase activity (releases free glucose at the branch point).
Glycogenesis Sequence
- 1Glucose-6-phosphate → glucose-1-phosphate (phosphoglucomutase)
- 2Glucose-1-phosphate + UTP → UDP-glucose (UDP-glucose pyrophosphorylase)
- 3Glycogen synthase adds glucose from UDP-glucose to the chain (alpha-1,4 bonds)
- 4Branching enzyme introduces alpha-1,6 bonds, creating branch points
Glycogenolysis Sequence
- 1Glycogen phosphorylase cleaves alpha-1,4 bonds at outer branches → glucose-1-phosphate
- 2Near a branch point, debranching enzyme transfers residues to expose the alpha-1,6 linkage (transferase activity)
- 3Debranching enzyme hydrolyzes the alpha-1,6 bond, releasing free glucose (alpha-1,6-glucosidase activity)
- 4Glucose-1-phosphate → glucose-6-phosphate → glycolysis (muscle) or blood glucose (liver, via glucose-6-phosphatase)
Glycogenesis vs. Glycogenolysis
| Feature | Glycogenesis vs. Glycogenolysis |
|---|---|
| Direction | Glucose → glycogen (storage) / Glycogen → glucose (mobilization) |
| Rate-limiting enzyme | Glycogen synthase / Glycogen phosphorylase |
| Activated intermediate | UDP-glucose / — |
| Main product released | Glycogen / Mostly glucose-1-phosphate, some free glucose at branches |
Common MCAT Trap
- Glycogen phosphorylase releases glucose-1-phosphate, NOT free glucose — only the debranching enzyme's glucosidase activity releases a small amount of free glucose.
- Muscle lacks glucose-6-phosphatase, so muscle glycogen can never raise blood glucose — only liver glycogen can.
- PDC (pyruvate → acetyl-CoA) is irreversible — once carbon becomes acetyl-CoA it cannot re-form glucose.
Quick Recall
What activated intermediate does glycogen synthase use?
What does glycogen phosphorylase release when it cleaves glycogen?
Why can't muscle release glucose into the blood?
What are PDC's two regulators?