Starvation

• Starvation begins at the start of the post-absorptive period
• Under normal circumstances, the brain can only use glucose
• Why can't the brain use FAs?

  They can't cross the BBB
• Glucose is transported into brain cells by GLUT1 transporters
• Although most of our energy is stored as fats, we cannot convert FAs into carbohydrates
• Acetyl CoA cannot be made into gluconeogenic precursors
• Parts of the kidney, skin, and RBCs have obligatory requirements for glucose
• General strategy during starvation:

  1. Conserve glucose
  2. Recycle glucose
  3. De novo glucose formation
• After a few hours of starvation, blood glucose levels are euglycemic
• What signals glycogenolysis?

  Glucagon binding to receptors on liver cell membranes
• Glucagon signalling pathway for glycogenolysis:

  1. Phosphorylase breaks glucose from glycogen and phosphorylates to become G1P
  2. G1P is rapidly isomerised to G6P
  3. G6P is transported into ER by G6P carrier
  4. G6Pase dephosphorylates G6P to become glucose
  5. Glucose diffuses out of the cell and into the blood via GLUT-2 transporters
• Phosphorylase breaks down glycogen by using phosphates to produce G1P
• glycogen contains the protein glycogenin which glucose residues are built onto
• What prevents glycogen chains from becoming too big?

  Glycogenin
• Phosphyrlase activation by glucagon:

  1. Glucagon binds to receptor
  2. Makes cAMP
  3. Causes PKA to become activated, resulting in a sequence of phosphorylation reactions
  4. Activates glycogen phosphorylase
• Debranching enzyme works to remove branches when they become short
• How does debranching enzyme work?

  transfer repeated units to the end of longer chains and hydrolyse the branch to release glucose
• Muscle does not breakdown glycogen much in starvation, because:

  • It has no glucagon receptors and no G6Pase
• Lypolysis mechanism

  1. Glucagon activates receptor on white adipose cell, causing the generation of cAMP
  2. cAMP increases the activity of PKA
  3. PKA phosphorylates hormone sensitive lipase, therefore activating it
  4. PKA also phosphorylates perilipin to allow interaction with activated HSL
  5. Lots of FAs and a glycerol are released into the blood
• What is released into the blood from lypolysis?

  Fatty acids and glycerol
• glycerol can also be converted into glucose in the liver via gluconeogenesis
• Cori-Cycle

  Process whereby lactate produced by the muscles are recycled to glucose in the liver
• perilipin is the shell surrounding the fat vacuole
• Euglycemic: Blood glucose levels are within the normal range
• Perilipin: A protein that coats lipid droplets
• Hypoinsulinemia leads to activation of proteases which breakdown proteins
• All amino acids need to be converted into just three types: alanine, glutamate, or aspartate
• Amine groups are transferred to acceptors by amino transferase:

  Pyruvate, α-ketoglutarate, or oxaloacetate
• Amination of pyruvate creates...

  Alanine
• Amination of α-ketoglutarate makes...

  glutamate
• Amination of oxaloacetate creates...

  aspartate
•  α-keto acids (carbon skeletons) are used in gluconeogenesis
• Acceptors put amine groups into the urea cycle
• Where does the urea cycle occur?

  In the liver
• The urea cycle consumes a lot of ATP
• What is the end product of the urea cycle?

  Urea
• What are the three rate-limiting steps bypassed in gluconeogenesis?

  hexokinase, phosphofructokinase, pyruvate kinase
• The complete gluconeogenesis pathway only occurs in the liver
• all enzymes involved in gluconeogenesis occur in the cytoplasm, except for pyruvate carboxylase which is in the mitochondria
• Substrates of gluconeogenesis

  lactate, glycerol, amino acid skeletons