Glycogen Metabolism and Gluconeogenesis

Study Notes

Goal: Understand glycogen metabolism and gluconeogenesis.
Objectives:
- Explain glycogenesis and glycogenolysis.
- Explain gluconeogenesis.
- Explain the regulation of these processes.
- Apply knowledge to real-world or clinical scenarios.
Keywords: glycogenesis, glycogenolysis, gluconeogenesis.
Reading: Essential Cell Biology, Alberts, Chapters 13 and 14, or any biochemistry textbook.

Glycogen: Storage form of glucose.
Structure: Polysaccharide.
Storage: Stored in liver and muscle; storage is limited. Once stores are full, no more glucose can be stored as glycogen.
Process: Glucose → glucose-6-phosphate (by hexokinase/glucokinase) → glucose-1-phosphate → uridine diphosphate glucose → glycogen.
Rate-limiting enzyme: Glycogen synthase.

Process: Glycogen → glucose-1-phosphate (by glycogen phosphorylase) → glucose-6-phosphate.
Liver: Glucose-6-phosphate → glucose (by glucose-6-phosphatase). Released into the blood for other tissues (especially brain).
Muscle: No glucose-6-phosphatase. Glucose-6-phosphate enters the glycolytic pathway.

Definition: Formation of glucose from non-carbohydrate sources.
Sources: Certain amino acids, lactate, glycerol, and Krebs cycle intermediates (e.g., oxaloacetate).
Location: Primarily in the liver and kidneys
Mechanism: Lactate and certain amino acids are converted to pyruvate, which is then converted to glucose via reverse glycolysis. Glycerol is converted to glyceraldehydes-3-phosphate, then glucose via reverse glycolysis.

Glycogenolysis Regulation:
- Rate-limiting enzyme: Glycogen phosphorylase.
- Stimulated by: AMP, glucagon (liver only), epinephrine.
- Inhibited by: ATP, insulin.
Glycogenesis Regulation:
- Rate-limiting enzyme: Glycogen synthase.
- Stimulated by: Insulin.
- Inhibited by: Glucagon, epinephrine.
Gluconeogenesis Regulation:
- Stimulated by: Glucagon.
- Inhibited by: Insulin.
Brain Glucose Uptake: Insulin is not required for the brain to take up glucose. Glucagon does not inhibit glycolysis in the brain. High glucagon, low insulin (e.g., starvation), allows the brain to use glucose from gluconeogenesis and glycogenolysis.