Glycogen is a branched polymer of glucose with 1,4 and 1,6 linkages.
Stored in liver (100 g), muscle (400 g), and brain (minimal supply).
Glycogen synthesis occurs when excess glucose is available.
Glycogen Synthesis (Glycogenesis)
Triggered by raised blood glucose levels (BGL) leading to increased insulin levels.
Insulin promotes glucose entry in muscle and stimulates glycogen synthetase for glycogen formation.
Glucose entry in the liver is insulin-independent but glucose concentration dependent.
Initiation of Glycogen Synthesis
Begins with protein glycogenin acting as a primer for polymerization.
Glycogenin undergoes auto-glucosylation using UDP-Glc.
Glycogenin forms a dimer and polymerizes glucose residues to form a short -(1,4)-Glc chain.
Elongation and Branching
Elongation by glycogen synthase isoforms (Gsy1p or Gsy2p) adding Glc in an -(1,4)-linkage.
Branching by Glc3p enzyme forming -(1,6)-linkages.
Regulation of Glycogen Synthesis
Glycogen synthase is regulated through phosphorylation (inactive) and dephosphorylation (active).
Insulin increases the active form of glycogen synthase.
High glucose 6-phosphate levels also stimulate glycogen synthesis.
Energy Considerations
Substantial glycogen synthesis requires sufficient energy and insulin.
Processes involving high energy phosphates are inhibited during energy depletion.
Glycogen Breakdown (Glycogenolysis)
Occurs during glucose deficiency, stimulated by glucagon and adrenaline.
Glycogen phosphorylase breaks down glycogen to glucose-6-phosphate (G6P).
Liver converts G6P to glucose; muscle/brain use G6P locally.
Enzyme Systems in Glycogen Metabolism
Separate enzyme systems for glycogen synthesis and breakdown.
Glycogen synthase and glycogen phosphorylase are the chief enzymes, regulated by hormones like insulin, glucagon, and epinephrine.
Clinical Connections
Deficiency in glycogenin or glycogen synthase leads to metabolic abnormalities.
Glycogenin-1 deficiency can cause glycogen depletion in muscle and cardiac tissues, leading to symptoms such as dizziness and cardiac problems.
Conclusion
Glycogen serves as a critical energy store regulated by complex hormonal and enzymatic interactions.
Understanding the synthesis, regulation, and breakdown of glycogen has implications for managing metabolic disorders and understanding energy utilization in tissues.