Chapter 15 Principles of Metabolic Regulation: Glucose and Glycogen

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Chapter 15Principles of Metabolic
RegulationGlucose and Glycogen
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Glycogen

• Polymeric form of glucose in animals
• (?1-4)Glc, branched (?1-6)Glc every 8-12 residues
• ? 50,000 subunits
• Muscle stores contain lt1 hour (rigorous exercise)
• Liver stores contain 12-24 hours
• Energy in FAT gtgt Energy in glycogen, but animals
  CAN ONLY convert fat into acetyl-CoA

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Reactions

• Glycogen phosphorylase

Pyridoxal phosphate is coenzyme for glycogen
phosphorylase
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Reactions of glycogen metabolism

• GP reactions continue (at non-reducing end) until
  it reaches 4 glucose units from branch
• De-branching enzyme catalyzes 2 sequential
  reactions
• Transfer of 3 glucose units to non-reducing end
  of chain
• Glucosyl residue at branch (?1-6) is hydrolyzed
  to glucose
• GP continues
• G-1-P is mutated by phosphoglucomutase to G-6-P
• In Liver, glucose from glycogen replenishes blood
  glucose in other tissues, glucose is oxidized in
  glycolytic pathway for energy
• Glycogen is synthesized from UDP-glucose as the
  sugar carrier

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Glycogen Breakdown
NEW SLIDE
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Glycogen SynthesisNT-glucose is sugar carrier
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??G -19.2 kJ mol-1
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Glycogen Synthesis
NEW SLIDE
New glycogen molecules (de novo synthesis) are
produced by priming protein glycogenin.
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Flux
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Potential Modes of Regulation
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Summary

• Flux of metabolites through a pathway is
  constant flux through R.D. step determines rates
  of subsequent steps
• Regulation maintains ?constant concentrations of
  important metabolites, but changes when needed
• Some reactions (e.g., in glycolysis) are near
  equilibrium others are not and are highly
  exergonic. These are OFTEN sites of enzyme
  regulation.
• Several modes exist for enzyme regulation
• Allosteric regulation is used for fast control of
  metabolites hormones and other extracellular
  signals are for slower control

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Regulation of Hexokinase IV
When glucose is high, HK-IV is allowed into
cytosol (active) When F-6-P is high, HK-IV is
sequestered in nucleus (inactive)
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F-6-P ? F-1,6-BPby PFK-1 is1st committed step
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Pyruvate kinase regulation
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Gluconeogenesis Regulation
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Up-regulates glycolysisDown-regulates
gluconeogenesisFormed by PFK-2 degraded by
FBPase-2 (Same enzyme!)
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