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Glycogen Metabolism and Regulation of Metabolic Pathways

Glycogen Metabolism Overview

  • Glycogen is a major form of carbohydrate storage in animal cells.
  • It is made of glucose monomers linked by glycosidic bonds, primarily in the liver and muscle.
  • Composed of two types of glucose polymers: amylopectin (branched) and amylose (linear).

Key Definitions and Concepts

  • Polysaccharides: Long chains of monosaccharides; important for energy storage (starch, glycogen) and structure (cellulose).
    • Glycogen: Homopolymer of glucose (α1-4 linkages with α1-6 branches).
    • Starch: Main energy store in plants; consists of amylopectin and amylose.
    • Cellulose: Structural polysaccharide in plants, made up of β1-4 linked glucose, which humans cannot digest.

Glycogen Structure

  • Glycogen Granules: Structure contains Glycogenin (core protein), with glucose chains radiating outward.
  • Branching: Glycogen branches every 8-12 glucose units, enhancing solubility and mobilization.

Glycogen Storage

  • Major storage sites are the liver (regulates blood glucose) and muscles (used during muscle activity).
  • Storing glucose as glycogen prevents osmotic imbalance in cells.

Glycogen Metabolism

  • Glycogenolysis: Breakdown of glycogen into glucose-1-phosphate (G1P).
    • Key Enzymes:
    • Glycogen Phosphorylase: cleaves glucose from glycogen.
    • Phosphoglucomutase: converts G1P to glucose-6-phosphate (G6P).
    • Glucose-6-Phosphatase: converts G6P to glucose in liver (not present in muscle).
    • Debranching Enzyme: removes branch points in glycogen.

Glycogen Synthesis (Glycogenesis)

  • Glycogen Synthase: Enzyme that adds glucose units to the glycogen chain.
    • Enzymatic Reactions in Glycogenesis:
    • Hexokinase converts glucose to G6P.
    • Phosphoglucomutase converts G6P to glucose-1-phosphate (G1P).
    • UDP-glucose pyrophosphorylase converts G1P to UDP-glucose.
  • Branching Enzyme: Forms α1-6 bonds and creates branches in glycogen.

Regulation of Glycogen Metabolism

  • Hormonal Regulation:
    • Insulin: Promotes glycogen synthesis and inhibits glycogenolysis (lowers blood sugar).
    • Glucagon and Epinephrine: Stimulates glycogen breakdown (raises blood sugar).
  • Allosteric Regulation:
    • ATP/G6P inhibit phosphorylase (inactive), while AMP activates it.
  • Covalent Modification:
    • Glycogen phosphorylase is activated by phosphorylation and are inhibited when dephosphorylated.
    • Glycogen synthase is inactivated by phosphorylation and activated in its dephosphorylated state.

Glycogenolysis Detailed Process

  • Glycogen Phosphorylase: Catalyzes the release of glucose-1-phosphate from glycogen.
  • Debranching Enzyme: Has two activities—transferring glucosyl residues and removing the last glucose residue as free glucose.
  • Phosphoglucomutase: Necessary for converting G1P to G6P, which enters glycolysis or is converted back to glucose.

Glycogenesis Detailed Process

  • Features of UDP-Glucose in glycogen synthesis:
    • Acts as a donor of glucose to glycogen chains.
  • Branching Enzyme introduces branches using a UDP-Glucose substrate.

Metabolic Pathways

  • Glycogenolysis pathway leads to glucose-6-phosphate which can enter glycolysis.
  • Glycogenesis pathway starts with glucose uptake via GLUT4 transporters, important in muscle cells during insulin signaling.