PATHWAYS: GLYCOGEN & GLUCOSE ¹

Carbohydrate Glycogen   Glycogen Synthesis   Glycogenolysis   Structure Regulation   Disorders Glycolysis Glucose to Pyruvate   Animation Polyglucosan Also see   Lipid metabolism

From: R Brian Sommerville

Also see: MedicalBiochemistry

Progressive changes Glycolysis of glucose to pyruvate. = Adenosine = Phosphate From University of Virginia

Glycogen: Synthesis & Degradation Pathways & Structure

• Disorders
• Synthesis: Enzyme Components
  • Glycogenin-1 (GYG): Autoglycosylation
    • Forms initial linear (1→4)-α glycosidic glucan chain: ~ 10-20 Glucose residues
  • Glycogen Synthase (GS)
    • Elongates glucan chain by adding glucose residues to non-reducing end
  • Glycogen Branching Enzyme (GBE)
    • Transfers 6-8 glucose residues
      • From: Nonreducing end of glucan chain
      • To: Carbon-6 atom of glucose residue in another chain
    • Creates branched (1→6)-α glycosidic linkage
• Degradation: Glycogenolysis Pathway

  Cytoplasm Glycogen Phosphorylase (PYGM; GP) Removes glucose residues from α-(1,4)-linkages Location: Glycogen carbohydrate straight chains Activity ceases 4 glucose residues away from an (1→6)-α glycosidic branch point Product of reaction: Glucose-1-phosphate Debrancher enzyme (GDE) Removes glucose from branch points (α-(1→6)-linkages) within glycogen Transferring 3 glucose residues to another non-reducing end of a glycogen chain Hydrolyzes 4th glucose residue at branch point: Releases free glucose Lysosomal: Acid α-glucosidase (GAA) Hydrolyzes α-(1→4) glycosidic bonds Releases: Glucose-1-phosphate Later steps Phosphoglucomutase Converts glucose-1-phosphate to glucose-6-phosphate Skeletal muscle: Glucose-6-phosphate is metabolized by the glycolytic pathway Diseases: CDG1t; GSD14 Phosphorylase b kinase Reactivates Phosphorylase: Via Phosphorylation Hexokinase Phosphorylates glucose Phosphorylated glucose: Enters glycolytic pathway

  Glycogenolysis: Cytoplasmic PYGM removes glucose-1-P from α-(1→4) glycogen straight chains

• Glycogen: Structure
  • General
    • Glycogen forms: Globular & Branched
    • Optimizes: Storage & Utility
  • Covalent bonds between glucose residues
    • (1→4)-α linkages: Join glucose molecules linearly
    • (1→6)-α linkages: Introduce a tree-like branching pattern
  • Linear chains of glycogen contain
    • ~10-14 glucose units with ≤ 2 branch points
    • Branch points: Separated by ≥ 4 monomer units
  • Macromolecules (β particles)
    • Contain: 50,000 glucose residues
    • Shapes: Irregular, Globular, Diameters 20 - 40 nm
    • Core: Spherical
    • Periphery: Less dense; Dispersed branches at edges
  • α particles: Large composite molecules
    • Formed by bound aggregation of multiple β particles
    • Diameter: 200 nm in diameter
    • Structure: Rosette-like
  • Protein core
    • Contents: Glycogenin & other glycogen synthetic molecules
    • Glycogenin: May form linkage for formation of α particles
  • Phosphate
    • 1 moiety/500 to 2500 glucose units in glycogen
    • Monoesters
    • Attached to: C2, C3 and C6 hydroxyls of glucose moieties
    • Higher concentration of phosphates in glycogen inner core
    • Phosphorylation: Increases glycogen solubility
• Structure regulation
  • Laforin
    • Regulates glucan chain length & Phosphorylation levels
    • Glycan phosphatase
    • Dependent on malin
    • Lafora disease: Poorly soluble glycogen
  • Malin
    • E3 ubiquitin ligase
    • Marks proteins for proteasomal degradation
    • Ubiquitination effect: Depends on laforin
    • Ubiquitiated proteins: GS, GDE, PP1 R5/PTG, R6
  • Other associated molecules
    • Starch-binding domain-containing protein 1 (STBD1)
    • AMP-activated protein kinase (AMPK)
    • Phosphorylase kinase (PhK)
    • Protein phosphatase 1 (PP1)