Regulators of glucose/ carbohydrate metabolism

4.8
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Introduction: Concept of energy state of our body:

  • High energy state/ Fed state: Defined as high ATP, high NADH, high insulin level (to facilitate the uptake of extra glucose into the cells)
  • Low energy state/ Fasting state: Defined as high AMP, high NAD, high glucagon level (to raise the concentration of glucose in the blood).

 

In high energy state:

  1. Glycolysis is promoted (insulin promotes glycolysis)
  2. Glycogenolysis should be inhibited (to prohibit further glucose to come into circulation from glycogen)
  3. Gluconeogenesis should be inhibited (gluconeogenesis is synthesis of glucose from non-carbohydrates)
  4. Lipolysis and Beta-oxidation of fat should be inhibited (to prohibit further energy production)
  5. Fat synthesis should be promoted (to channelize extra amount of glucose into fat)
  6. Glycogen synthesis should be promoted (to channelize extra amount of glucose into glycogen).

 

Similarly, in low energy state:

  1. Glycolysis is inhibited (glucagon inhibits glycolysis)
  2. Glycogenolysis should be promoted (to facilitate more glucose to come into circulation from glycogen)
  3. Gluconeogenesis should be promoted (gluconeogenesis is synthesis of glucose from non-carbohydrates)
  4. Lipolysis and Beta-oxidation of fat should be promoted (to increase the energy production)
  5. Fat synthesis should be inhibited
  6. Glycogen synthesis should be inhibited.

 

In a summary, priorities of the body are:

Process

High energy state Low energy state
Glycolysis

Glycogenolysis

Gluconeogenesis

Beta oxidation of fat

Lipolysis

Fat synthesis

Glycogen synthesis

 

Now we have to know the rate limiting enzymes of each of the process:

Process

Rate limiting enzyme
Glycolysis

PFK-1

Glycogenolysis

Glycogen phosphorylase
Gluconeogenesis

Fructose 1,6 bisphosphatase

Beta oxidation of fat

CAT-I
Lipolysis

Hormone sensitive lipase

Fat synthesis

Acetyl CoA carboxylase
Glycogen synthesis

Glycogen synthase

 

You can see the list of all rate limiting enzymes from here.

 

Now you just have to correlate. Let’s solve some questions.

Question no 1:

Which of the following enzyme activity decreases in fasting? (Nov. AIIMS 2018)

  1. Hormone sensitive lipase
  2. Glycogen phosphorylase
  3. Acetyl CoA carboxylase
  4. PFK1.

 

Explanation & Approach:

  • Fasting = Low energy state
  • Priorities of the body are:

Process

Low energy state

Enzyme

Glycolysis

PFK-1
Glycogenolysis

Glycogen phosphorylase

Lipolysis

Hormone sensitive lipase
Fat synthesis

Acetyl CoA carboxylase

 

So, both C & D are correct. D being a better answer as in fasting state, glucagon is the most important hormone working and glucagon inhibits glycolysis.

 

Question no 2:

Which of the following is an allosteric activator of muscle glycogen phosphorylase?

  1. ATP
  2. NADH
  3. 5′ AMP
  4. Glucose.

 

Explanation & Approach:

  • Glycogen phosphorylase is the rate limiting enzyme of glycogenolysis
  • Activator of Glycogen phosphorylase means activator of glycogenolysis
  • Activated/ increased glycogenolysis occurs when the body energy state is low (so that glycogen can break down to give extra glucose, i.e. extra energy)
  • Low energy state = High AMP
  • So, high AMP is allosteric activator of glycogen phosphorylase.

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