Glycogenesis (Glycogen Synthesis)
| Rate-Limiting Enzyme: | Glycogen Synthase |
| Activated Substrate: | UDP-Glucose (Synthesized by UDP-Glucose Pyrophosphorylase) |
| Branch-Forming Enzyme: | Branching Enzyme (α(1→4) to α(1→6) transglucosidase) |
| Cellular Location: | Cytosol (Mainly liver and skeletal muscle) |
High-Yield Core Realities:
- The Primer Requirement: Glycogen synthase cannot start a chain from scratch. It requires Glycogenin, a self-glycosylating core protein that attaches the initial short tyrosine-linked glucose primer chain.
- Covalent Regulation Inverse Rule: Unlike breakdown enzymes, Glycogen Synthase is ACTIVE when DEPHOSPHORYLATED (Synthase a) and INACTIVE when PHOSPHORYLATED (Synthase b).
- Hormonal Activation (Insulin): Insulin activates Protein Phosphatase 1 (PP1), which strips the phosphate groups off Glycogen Synthase, rapidly turning synthesis ON in the well-fed state.
- Hormonal Inactivation (Glucagon/Epinephrine): Act via cAMP and Protein Kinase A (PKA) to phosphorylate Glycogen Synthase, shutting synthesis OFF during fasting or stress.
- GSD Type IV (Andersen Disease): Genetic deficiency of the Branching Enzyme. Results in the synthesis of abnormal, long, unbranched outer glycogen chains (called polyglucosan bodies) that act like foreign objects, triggering a severe immune response, progressive cirrhosis, hepatosplenomegaly, and death in early childhood.