10 - Glycogenolysis + Glycolysis 1

• How is the branching structure of glycogen useful in its breakdown?

  Can be broken down rapidly as multiple branches can be worked on at once
• Describe the first step of glycogen degradation

  Glycogen Phosphorylase cleaves it's substrate by the addition of an inorganic phosphate, yielding Glucose-1-Phosphate. This is carried out sequentially down the chain
• How is Debranching carried out?

  - Phosphorylase cleaves to within 4 glucose residues of the branch point, and then oligo(a1,4>a1,4)glycantranserase, or debranching enzyme, transfers the 3 end residues to the end of another branch

  - The single remaining glucose at the branch point is removed by a(1,6)glucosidase
• What enzyme catalyses the conversion of Glucose-1-phosphate to Glucose-6-Phosphate?

  Phosphoglucomutase (reversible reaction)
• What can the Glucose-6-phosphate be used in?

  Glycolysis, or in the liver and kidney, it can be converted back to glucose and released into the blood
• What enzyme carries this out?

  Glucose-6-Phosphatase
• Why can the liver and kidney carry out this function?

  - Liver for glucose homeostasis

  - Kidney for the Reabsorption of Glucose
• How are glycogenesis and Glycogenolysis controlled?

  Allosterically by Glucose-6-Phosphate
• Describe this control


  - Glucose-6-Phosphate inhibits and reduces the activity of glycogen phosphorylase

  - Glucose-6-Phosphate increases the activity of Glycogen synthase

  - When G6P is high, glycogen synthesis is encouraged and glycogen breakdown is inhibited
• What is this a good example of?

  Reciprocal control
• What does this control prevent ?

  Prevents a futile cycle and energy waste, whilst one enzyme is active, another is inactive
• What are insulin and glucagon?

  Peptide hormones secreted from the pancreas. Insulin is secreted when blood glucose is high and glucagon is secreted when blood glucose is low.
• Where are they secreted from?

  The pancreas contains clusters of endocrine cells called islets of langerhans

  - Insulin is secreted by B cells

  - Glucagon is secreted by a cells
• When is insulin secretion stimulated?

  When glucose levels rise above 5mmol/L
• What does insulin stimulate?

  - Glycogen synthesis

  - Glycolysis
• What is Glucagon suppressed by?

  A rise in glucose levels
• How is Glycogen synthase regulated by insulin?

  - Insulin binds to receptor

  - Protein phosphatase is activated

  - Protein phosphatase desphosphorylateds glycogen synthase, activating it
• How is Glycogen synthase regulated by glucagon and adrenaline

  - Glucagon and adrenaline bind to receptors

  - A rise is cAMP activates a protein kinase

  - Glycogen synthase is phosphorylated, inhibiting it
• How is Glycogen Phosphorylase regulated by insulin

  - Insulin binds to receptor and activates proetin phosphatase

  - Protein phosphatase dephosphorylates phosphorylase kinase a, de-activating it

  - Glycogen phosphorylase is dephosphorylated, inactivating it and shutting down glycogen breakdown
• Describe how Glycogen Phosphorylase is regulated by adrenaline and glucagon

  - Adrenaline and Glucagon bind to receptors, activating adenylate cyclase

  - ATP is converted to cAMP, activating protein kinase

  - Phosphorylase Kinase a is phosphorylated activating it

  - Phosphorylase kinase a phosphorylates Glycogen phosphorylase, meaning glycogen is broken down
• What happens to Glycogen levels after a meal?

  - increased insulin stimulates glycogen synthesis

  - From 100g, about 25g is stored as glycogen, and 75g is oxidised by glycolysis
• What is glycolysis?


  A 10 step process with an investment phase and pay-off phase
• Give a brief overview of glycolysis

  - Glucose is converted to 2 molecules of pyruvate

  - two molecules of ATP are synthesised

  - Oxygen is not required, anaerobic process
• What can the pyruvate molecules be used in?

  Citric acid cycle
• Which steps of the investment phase are regulated?

  Step 1 and Step 3, as they are irreversible
• Describe Step 1


  - Catalysed by Hexokinase or Glucokinase

  - Glucose is phosphorylated to Glucose-6-Phosphate by the addition of ATP
• Describe step 2


  - Catalysed by Glucose-6-phosphate isomerase

  - Glucose-6-phosphate is converted to D-Fructose-6-phosphate

  - This means Carbon 1 is available for phosphorylation
• Describe step 3


  - Catalysed by phosphofructokinase

  - Extremely tightly regulated

  - Fructose-6-phosphate is phosphorylated by ATP to form Fructose 1,6-bisphosphate, an unstable molecule
• Describe step 4


  - Catalysed by fructose 1,6-bisphosphate aldolase

  - Fructose 1,6-bisphosphate is cleaved to Glyceraldehyde-3-phosphate (GADP) and Dihydroxyacetone (DHAP)
• Describe Step 5


  - DHAP is rearranged to GHAP so both can be used

  - This is catalysed by triosephosphate isomerase