Glycogen & HMP Shunt

Question 1

Structure of glycogen

Answer 1

• Highly branched polymer of glucose monomers

Question 2

Locations of glycogen in body

Answer 2

• Liver
  
  • 20%, 100g
• Muscle
  
  • 80%, 400g

Question 3

Importance of glycogen structure

Answer 3

• Represents pool of stored glucose that can be rapidly mobilized
• Increases amount of glucose available between meals

Question 4

Location of glycogen synthesis in body

Answer 4

• Most prominent in:
  
  • Liver
  • Skeletal muscles

Question 5

Glycogen synthesis pathway

Answer 5

• Utilizes uridine diphosphate (UDP-glucose)
  
  • Activated form of glucose
  • Synthesized from G1P and UTP
  • Not G6P or G1P
• First step: conversion of G6P to G1P
  
  • Enzyme: phosphoglucomutase
• Glycogen synthase catalyzes transfer of UDP-glucose to growing chain: IMPORTANT REACTION
  
  • Key regulated enzyme in glycogen synthesis
  • Can add glucose residues only if polysaccharide chain has been initiated and already contains more than 4 glucose residues
• Branching enzyme forms a-1,6-linkages
  
  • Glycogen synthase adds glucose until 11 units are reached
  • Then branching occurs - 6-7 glucose residues transferred to internal site
  • Increases the solubility of glycogen
  • Effectively increases rate of synthesis and breakdown

Question 6

Glycogen breakdown pathway (glycogenolysis)

Answer 6

3 steps:

• 1. Release of glucose-1-phosphate from glycogen.
• 2. Remodeling of glycogen substrate to permit further degradation.
• 3. Conversion of glucose-1-phosphate into glucose-6-phosphate for further degradation

3 enzymes:

• Glycogen phosphorylase** - key regulated enzyme in glycogenolysis
• Debranching enzyme
• Phosphoglucomutase

Question 7

Reactions catalyzed by glycogen phosphorylase

Answer 7

• Catalyzes phosphorolytic cleavage of glycogen into glucose-1-phosphate.
• Phosphorylase is key regulatory enzyme in glycogenolysis.
• Key reaction:
  
  • Glycogen (n residues) + Pi –> Glucose-1-phosphate + Glycogen (n-1 residues)

Question 8

Reactions catalyzed by glycogen synthase

Answer 8

• Catalyzes transfer of glucose from UDP-glucose to growing glycogen chain.
• Activated UDP-glucose transferred to hydroxyl group at C-4 terminus of glycogen to form a-1,4 glycosidic linkage.
• Key regulated enzyme in glycogen synthesis.
• Can add glucose residues ony if polysaccharide chain has been initiated and already contains more than 4 glucose residues

Question 9

Coordinate regulation of glycogenesis/glycogenolysis

Answer 9

• Both regulated by hormones: insulin and glucagon
• Regulate the activity of key enzymes through reversible phosphorylation

Question 10

Metabolic conditions favoring glycogen synthesis

Answer 10

• When substrate availability and energy levels are high
• Occurs in liver when body is well fed
• Occurs in skeletal muscle as soon as muscle is at rest

Question 11

Metabolic conditions favoring glycogenolysis

Answer 11

• When energy levels and glucose supplies are low
• Occurs in liver during periods of fasting
• Occurs in skeletal muscle during active exercise

Question 12

Stimuli of glycogenolysis

Answer 12

• Glucagon or epinephrine binding to receptors signals need for glycogen to be degraded to either elevate blood glucose or provide energy for exercising muscle
• Calcium release in cell during muscle contraction
• AMP

Question 13

Stimuli of glycogen synthesis

Answer 13

• Glycogen synthase = crucial.
• When phosphorylated by glycogen synthase kinase (GSK) it is deactivated.
• Likewise when dephosphorylated it is activated.
• Enzyme managing dephosphorylation of glycogen synthase = protein phosphatase 1 (PP1).
• G6P allosterically activates glycogen synthase when inactivated, making it a better substrate for PP1.
• Insulin stimulates glycogen synthesis by dephosphorylating (and activating) PP1 which allows PP1 to dephosphorylate (and activate) glycogen synthase.
• Insulin also inactivates GSK