MCB Lecture 15, Allosteric regulation and Tissue specificity

Question 0

Which steps of glycolysis have Allosteric regulation?

Answer 0

1. Glucose -> Glucose-6-phosphate
2. Fructose-6-phosphate -> Fructose-1,6-bisphosphate
3. Phosphoenolpyruvate-> pyruvate

Question 1

Give a one sentence definition of Allosteric regulation

Answer 1

Allostery is the change in shape and activity of an enzyme when a regulatory molecule binds so e where else on the enzyme (not the active site)

Question 2

Which is the most important control point of cellular respiration?

Answer 2

Fructose-6-phosphate -> Fructose-1,6-bisphosphate

Question 3

What shape is the graph depicting the dependence of V0 on [S]?

Answer 3

Sigmoidal, it’s a combination of two Michaelis-Menten graphs

Question 4

What are the T and R states?

Answer 4

T- inhibited state, low enzyme activity (tense state; can’t get any work done)
R- enhanced state, higher enzyme activity (relaxed state, can get work done)

Question 5

What causes the enzyme to enter the R state?

What causes the enzyme to enter the T state?

Answer 5

Substrate binding stabilises the R state

Activators –> R state

Inhibitors –> T state

Question 6

How does the V0 vs. [S] graph curve change for the T and R states?

Answer 6

The curves have a more M-M shape

Question 7

Describe Allosteric regulation of hexokinase

Answer 7

Hexokinase is only allosterically changed in the muscles.

Glucose-6-phosphates acts as an inhibitor to Hexokinase

Question 8

Why are there two forms of enzymes for the steps of glycolysis?

Answer 8

The liver and the muscles have different versions of these enzymes

Question 9

What is the other name for hexokinase?

Answer 9

Glucokinase

Question 10

Describe Allosteric regulation of Phosphofructokinase-1.

Answer 10

There are two different versions; one for liver, one for muscle tissue.
However, the same molecules act as activators and inhibitors

Activation: ADP, Fructose-2,6-phosphate, AMP

Inhibition: ATP, citrate, high [H]

Question 11

What is the difference between Allosteric regulation of phosphofructokinase in the liver and muscles?

Answer 11

None, only different enzyme

Question 12

Describe the Allosteric regulation of pyruvate kinase

Answer 12

Different enzyme in muscles and liver, however, same inhibition and activation

Activation: F-1,6-bisphosphate
Inhibition: ATP, alanine

Question 13

Describe the differences in Allosteric regulation of Pyruvate Kinase in the liver and in the muscles

Answer 13

Only different enzyme

Question 14

Describe the differences in Allosteric regulation of hexokinase in the liver and in muscle tissue

Answer 14

Glucose-6-phosphate acts as an inhibitor only in the muscles. No Allostery in the liver.

Different forms of the enzyme

Question 15

Compare and contrast the fuel sources of the brain, muscle, liver and adipose

Answer 15

Brain : only glucose. Ketone bodies during starvation
Muscles : glucose, fatty acids and ketone bodies
Adipose : glucose required to synthesis triacylglycerol
Liver : glucose, amino acids, fatty acids, ketone bodies but prefers alpha keto acids (from amino acid breakdown)

Question 16

Compare and contrast fuel storage in the brain, muscles, adipose and liver

Answer 16

Brain : none
Muscles : 75% of body’s glycogen stored here
Adipose : triacylglycerol
Liver: 25% of body’s glycogen

Question 17

Compare and contract the resting state conditions in the brain, muscles, adipose and liver

Answer 17

Brain : uses 60% of daily glycogen
Muscle : fatty acids are main fuel source
Adipose: mainly active during starvation: breakdown of triacylglycerol
Liver: gluconeogenesis during starvation or fasting, Fatty acid oxidation for energy, and Ketone body oxidation for the brain and heart

Question 18

Under starving conditions, the brain can adapt to which fuel source?

Answer 18

Ketone bodies

Question 19

Which fuel source does the heart muscle use?

Answer 19

Acetoacetate in preference to glucose