Metabolic Regulation

Question 1

Metabolic regulation

Answer 1

Controlling the flow of nutrients along metabolic pathways.

Allows us to live normal lives despite fluctuations in intake and expenditure of energy.

Question 2

Main characteristics of metabolic regulation

Answer 2

1. Different distribution of nutrients in different tissues.
   - Ex: glycogen in muscle VS. liver
2. Different enzymes (isoforms) in different tissues.
   - Ex: Glucose transporters.
   Brain => high affinity
   Liver => low affinity
   GLUT 4 => exposed in response to insulin (Muscle and adipose tissues) in order to decrease glycemia.
3. Rapid changes in enzyme activity.
   - Ex: phosphorylation / dephosphorylation of enzymes.
4. Changes in amount of enzymes
   - Changes in gene expression.
   Ex: Exposure to insulin:
   - Increase gene expression of lipogenic gene.
   => favor fat deposition (fat synthesis).
   - Decrease hepatic gluconeogenesis.

Question 3

Post-absorptive state

Answer 3

• From 6hours – 8hours AFTER a meal onwards. Whenever absorption stops from gastrointestinal tract.
• Low / no insulin, high glucagon.

Question 4

Post-absorptive state in liver

Answer 4

=> Secrete glucose in blood (to maintain glycemia constant)
- 50% glycogen breakdown (Glycogenolysis)
- 50% gluconeogenesis
Carbon sources:
- Glycerol
- AA (muscle)
- Lactate (muscles, red blood cells)
=> Production and secretion of Ketone Bodies.
• Concentration rise 12-16 hours after meal.
• Unimportant unless prolonged fasting.

Question 5

Post-absorptive state in Adipose Tissue

Answer 5

• LIPOLYSIS → TAG → fatty acids = highest concentration, major source of energy.
  TAG → Release glycerol in blood (for gluconeogenesis)

Question 6

Post-absorptive state in Brain

Answer 6

→ Glucose uptake (60% glucose produced by liver)
- Produce ATP
→ Ketone bodies uptake
- Depends on availability! (only prolonged starvation)
- To produce ATP

Question 7

Post-absorptive state in other tissues

Answer 7

ATP production
- Glucose uptake (limited)
- Fatty acids uptake (muscle)
- Ketones body
=> Depends on availability

Question 8

Absorptive state

Answer 8

=> 15min after a meal lasting 4-5hours
- Increased glycemia (immediate) = Increased insulin
- Absorption from gastro-intestinal tract
=> Increase TAG in plasma (after 3-5 hours)

Question 9

Absorptive state in Liver

Answer 9

• Suppression of glucose release
• Glucose UPTAKE (=> GLUT2 works as glycemia increased)
  => ATP production
• Synthesis of GLYCOGEN
• Synthesis of TAG (excess of glucose)
  =>Released in VLDL, store in
  adipose tissues.
• Uptake of Lactate (from glucose metabolism in muscle and erythrocytes). Converted into G-6-P through gluconeogenesis which is then converted to Glycogen.
• Uptake of excess AA
  => Protein synthesis
  => Production ATP

Question 10

Absorptive state in Muscle

Answer 10

-Uptake of glucose (exposure of GLUT 4 because of increased insulin).
=> Synthesis of GLYCOGEN
=> ATP production
=> Lactate
- Insulin suppress lipoprotein lipase (no uptake of fatty acid from TAG)
=> physical activity CAN: increase
LPL activity.
Uptake fatty acids from TAG
=> ATP production
=> local TAG storage
- AA uptake => protein synthesis
=> excess: ATP production

Question 11

Absorptive state in Adipose tissue

Answer 11

- Insulin suppress Lipolysis
   => fatty acids concentration in blood 
        drops.
- Uptake of GLUCOSE (exposure of 
   GLUT4)
    => ATP production
    => glycerol synthesis
- Insulin ACTIVATE LPL
    => uptake of fatty acid from 
         circulating TAG.
- Glycerol + Fatty acid → TAG synthesis + storage.

Question 12

Lipoproteins

Answer 12

Vesicles carrying TAG.
-VLDL (very low density lipoprotein):
=>From liver to tissues.
- Chylomicrons: From G.I. tract to liver.
- Lipoprotein lipase: in adipose tissue, splits TAG into fatty acid and glycerol so it can be absorbed by tissues.