Feed Fast Cycle

Question 1

How is metabolic homeostasis achieved?

Answer 1

Normal cell functions require a constant source of fuels regardless of food intake or fasting/starvation

Metabolic homeostasis in tissues results from the balance between

• storage of energy
• mobilization of stored energy

This is achieved with communication by:

• Blood with hormones or substrates
• Nervous

Question 2

Describe the general metabolic functions of insulin

Answer 2

Insulin is the major anabolic hormone and promotes storage of fuel or usage for growth

• Glycogenesis in liver and muscle
• fatty acid and TAG synthesis in liver (release of VLDL)
• protein synthesis in muscle and liver (serum proteins )

Question 3

What are the general metabolic functions of glucagon?

Answer 3

Glucagon is a major hormone for fuel immobilization

• Hepatic glycogen degradation and gluconeogenesis.
• Hepatic ketone body synthesis and release
• Low insulin/glucagon ratio in blood leads to TAG degradation in fat cells and to release of fat acids and glycerol

Question 4

What does insulin activate generally?

Answer 4

• glycolysis
• glycogen synthesis
• protein synthesis
• synthesis of fatty acids
• synthesis of cholesterol

Question 5

What does glucagon activate generally?

Answer 5

• Gluconeogenesis
• Glycogen degradation
• usage of amino acids for gluconeogenesis
• degradation of fatty acids
• synthesis of ketone bodies

Question 6

Give the general time frame of the feed state

Answer 6

The postprandial (absorptive ) phase is the time of the feed state with ongoing digestion and absorption after a meal (prandi) which is approximately 2 hrs after food intake

Question 7

What is the general time frame of the fasting state?

Answer 7

The post-absorptive phase is the time of the fasting where the food is completely digested and absorbed which is approximately 5 hrs after a meal or the time after an overnight fast

Question 8

Describe the early phase of starvation

Answer 8

Early phase of starvation starts about 3 days after last food intake. The time after 10 days of fasting/starvation can be seen as prolonged starvation

Question 9

What are the blood levels of insulin and glucagon after a glucose rich meal?

Answer 9

• Post-prandial increase of glucose leads to increase of insulin and decrease glucagon
• the insulin-glucagon ratio is high
• Note: the glucagon level drops only 25% and is ready to be raised during fasting

Question 10

How does the liver play a central role in reducing the rise of blood glucose after a meal?

Answer 10

• the liver receives blood from the portal vein containing dietary monosaccharides and insulin
• Insulin assures that sugars are trapped inside of the hepatocytes to reduce the rise of postprandial blood glucose levels and to support blood glucose homeostasis.

At very high blood glucose levels following extensive glycolysis, insulin stimulates the hepatic synthesis of fatty acids, TAGs and cholesterol. VLDLs are released into the blood

Question 11

Explain glucose uptake by insulin-dependent glucose transporters

Answer 11

GLUT-4 are mainly found in fat tissue and muscle

1. Insulin binds to its receptor in the cell membrane
2. Binding causes a signaling cascade that promotes recruitment of glucose transporters from intracellular pool to cell membrane
3. GLUT-4s increase insulin-mediated uptake of glucose into the cell
4. When insulin levels decrease, GLUT 4s move from the cell membrane to the intracellular storage pool, where they can be recycled
5. Vesicles fuse to from an organelle called the endosome

Question 12

Explain the general postprandial adipose tissue metabolism

Answer 12

After a meal insulin activates lipoprotein lipase in capillaries of adipose tissue and GLUT-4 transporters in the fat cell plasma membrane. Inside of fat cells insulin stimulates TAG synthesis

Lipoprotein generates free fatty acids
Glycerol 3-p from glycosidic and free fatty acids used for TAG synthesis and storage

Question 13

Describe postprandial muscle metabolism

Answer 13

High insulin levels

Insulin activates glucose uptake from blood (via GLUT-4) glycogen synthesis and glycolysis take place

Insulin activates amino acid uptake from the blood.
Protein synthesis is stimulated especially by leucine

Usage of branched-chain amino acids for protein synthesis and for energy metabolism

Question 14

How does availability of substrates from the blood determine the pathways of liver, muscle and fat?

Answer 14

High levels of blood glucose after a meal:

Liver: glycolysis, synthesis of glycogen, fatty acids, TAGs, cholesterol and VLDL

Muscle: glycolysis and glycogen synthesis

Fat cells: glycolysis and TAG synthesis

High levels of blood free fatty acids during fasting:

Liver: B-oxidation of fatty acids and ketone body synthesis
Muscle: B-oxidation of fatty acids and ketone body usage

Question 15

How does the liver regulate blood glucose AFTER A MEAL?

Answer 15

Uptake of dietary sugars reduces increase of blood glucose

Pathways: insulin stimulates hepatic :

1. Glycogen synthesis
2. Fatty acid synthesis
3. Cholesterol synthesis

Question 16

How does the liver regulate blood glucose DURING FASTING?

Answer 16

• release of free glucose into the blood prevents drop of blood glucose
• pathways : glucagon stimulates hepatic:
  1. Glycogen degradation
  2. Gluconeogenesis
  3. fatty acid degradation
  4. Ketone body synthesis

Question 17

What happens during fast/ starvation?

Answer 17

The liver regulates with great precision and speed the amount of glucose secreted into the blood

-the liver has to match the amount of gluc9se being removed and used by other cells

Question 18

What processes are affected by fasting liver metabolism?

Answer 18

Glycogen synthesis is 8nhibited

Glycolysis is inhibited

PPP is reduced

PDH is inhibited

TCA cycle is inhibited

Fatty acid synthesis is inhibited

Cholesterol synthesis is inhibited

TAG synthesis is inhibited

Whereas

Glycogen degradation is active
Gluconeogenesis is active(uses alanine, glutamine, lactate and glycerol in blood)

B-oxidation is active

Ketone body synthesis is active

Question 19

Describe fasting muscle metabolism

Answer 19

Low insulin and high cortisol

Free fatty acids and ketone body uptake from the blood for energy metabolism

• glycogen degradation and glycolysis occurs during muscle contraction
• protein degradation is stimulated by cortisol.

Amino acid release into blood, elevated alanine

Question 20

TAGs are degraded in fat cells resulting in the release of fatty acids and…

Answer 20

Glycerol into the blood

TAG degradation: hormone sensitive lipase is pgosphorylated and activate

Done with high epinephrine and cortisol

Question 21

What are allosteric regulators of gluconeogenesis in the liver?

Answer 21

ATP formation, NADH and Acetyl CoA are needed as allosteric regulators for gluconeogenesis

Question 22

How can pathways be changed within minutes in the feed fast cycle?

Answer 22

1. Availability of substrates in the blood or inside the cell compartment
2. Allosteric regulation by activators and inhibitors of rate-determining enzymes

Question 23

How can pathways of the feed fast cycle between minutes to hours?

Answer 23

Covalent modification of enzymes by:

1. Phosphorylation and de-phosphorylation
2. Proteolytic activation

Question 24

How can the feed fast cycle pathways between hours to days?

Answer 24

Amount of enzyme depends on induction or repression of enzyme synthesis