Monday, August 12, 2013

GPLase

Glycogen - Glycogen Catabolism

Allosteric enzyme cleaves Glycogen by acctacking GLC in the non reducing ends

Glycogen, Glucose

Fundamentals:

  • Regulation by several allosteric affectors
  • Reversible phosphorylation responsive to Hormones: Insulin, Epinephrine and Glucagon
  • Different structure and regulation but similar funcitons in distinct tissues

LOC:

Structures:

  • Phosphorylate a - R state (relaxed) ACTIVE
  • Phosphorylate a - T state (tense) INACTIVE
  • Phosphorylate b - R state (relaxed) ACTIVE
  • Phosphorylate b - T state (tense) INACTIVE

Isozymes:

  • Liver - GLC sensitive, AMP insensitive
  • Phosphorylase a is sensitive to GLC
    • Phosphorylase a is most responsive to R-T transition
      • GLC binding shifts equilibrium Phosphorylase a R into the T state
  • Skeletal Muscle - dimer, Intracelllar Energy Charge
  • R and T states (not discrete but usually active/inactive)
  • Phosphorylase a equilibrium favors R
  • Phosphorylase b equilibrium favors T
Regulation - hormones, AMP/ATP sensitive
Reguation - muscle contraction
  • Active during INC AMP concentrations/LOW energy charge
    • AMP binds to nucelotide binding sites to stabilize actie site
  • G-6P stabilizes the less active T state - Negative Feedback
  • ATP acts negative allosteric effector
  • Glucose 6-phosphatase absence = NO GLUCONEOGENESIS

Concepts:

Terminology: