Integration of Metabolism

Question 1

Explain the way these organs metabolise to gain energy:
Brain
Heart muscle
Adipose
Kidney
Liver

Answer 1

Brain:
• Uses 100-120g glucose daily - lacks energy stores
• Most of the energy is used for NA/K ATPase activity for maintaining membrane potentials and NT synthesis
• Glucose is moved into the cell by GLUT1/3 - has a low Km = saturated under most conditions
• Plasma glucose <2.2.mM is dangerous
• Normally, FAs is used for membrane biosynthesis instead of energy

Heart muscle:
• Only aerobic respiration occurs, even with little no glycogen stores
• FAs are the main energy source, followed by lactate and ketone bodies

Adipose:
• Energy reservoir in the form of TGs - transported to adipose via chylomicrons

Kidney:
• Small organs but have a high energy consumption (10% of total energy)
• During starvation, the kidneys produce half of the blood glucose via gluconeogenesis

Liver:
• Central role in regulating Carb/FA/AA metabolism - provides fuel for brain, muscle
• Most compounds absorbed by the gut pass through the liver via the portal system
• α-keto acids are its main energy source

Question 2

How do the liver and muscle work to maintain blood glucose?

Answer 2

Liver:
• Glucose is transported into Hepatocytes by GLUT2 (NOT INSULIN-SENSITIVE) - is immediately phosphorylated by Glucokinase
• G6P from glycogenolysis is dephosphorylated by G-6 Phosphatase
into glucose - is then moved out into blood by GLUT2

Muscle:
• Glucose is transported into Muscle cells by GLUT4 (INSULIN-DEPENDENT) - is immediately phosphorylated by Hexokinase
• Glycogen → glucose during exercise
• Glycolysis is a rapid source of ATP

Question 3

What occurs in the liver and muscle during a sprint?

What occurs in the liver and muscle during a marathon?

Answer 3

Short-term, high energy needed:
• Muscle ATP stores are small
• Glycogenolysis, followed by Glycolysis
• Creatine phosphate/CP – small ATP store
CP + ADP → Creatine + ATP - uses Creatine Kinase

• Anaerobic respiration produces lactate = ↓PH - lactate produced is moved to the liver to be converted back into glucose; Cori Cycle

Long-term energy needed:
• The ATP required is much more than how much the body’s glycogen stores can provide - both fats and glycogen stores used
• Aerobic respiration is more efficient as it uses the muscle, liver, and adipose tissue together – muscle alone isn’t sufficient
• Fats are a large energy source, but its metabolism is slower than glycogen and CP

Question 4

What are the body’s priorities when we stop eating?

How does the body do this?

Answer 4

• To maintain blood [glucose], and then to preserve protein

- Metabolism shifts from glucose to FA/Ketone bodies

Question 5

What occurs during:
Early Starvation (24hrs)?

Intermediate Starvation (3-20days)?

Prolonged Starvation (>3wks)?

Answer 5

• • Glucose released from liver due to gluconeogenesis and glycogenolysis
  • ↑Lipolysis = ↑FA (in adipose)
  • Muscles do ↓glucose metabolism
  • ↓Insulin in blood = ↓GLUT4 expression = ↓Glucose uptake in muscles
• • Glycogen stores depleted with an increased dependence on Lipolysis and Ketogenesis for energy
  • ↑gluconeogenesis to maintain blood glucose
• • *BRAIN STARTS TO USE KETONE BODIES INSTEAD OF GLUCOSE!
  • Kidneys do most of the gluconeogenesis
  • Proteolysis occurs; fueling gluconeogenesis