Regulation Of Protein Function

Question 1

How can we regulate enzyme activity - short term regulation

Answer 1

• substrate and product concentration

- change in enzyme conformation ( eg allosteric regulation , covalent modification , proteolytic cleavage )

Question 2

How can we regulate enzyme activity - long term regulation

Answer 2

• change in protein synthesis

- change is rate of protein degradation

Question 3

What is allostery ?

Answer 3

• condition of an enzyme by which the structure and activity of an enzyme is remodelled due to a a molecule binding.

Question 4

Outline what it means by an allosteric enzyme being in a ‘T’ state

Answer 4

• the allosteric enzyme has a low activity , low affinity

Question 5

Outline what it means by an allosteric enzyme being in the R state

Answer 5

• the allosteric enzyme is in a high affinity , high activity state.

Question 6

What is an allosteric effector and give a possible example

Answer 6

• a molecule that binds to an allosteric region of an enzyme for example 2,3 bisphosphoglycerate to haemoglobin

Question 7

What is the role of phosphofructokinase -1

Answer 7

• a key enzyme regulator in glycosis
• it catalyses the formation of fructose 1,6 bisphosphate from fructose-6-phosphate.
• uses ATP to do this too.

Question 8

What type of enzyme is phosphofructosekinase?

Answer 8

Allosteric enzyme

Question 9

How is phosphofructosekinase inhibited ?

Answer 9

• by high levels of ATP, CITRATE and H+

Question 10

How is phosphofructokinase activated ?

Answer 10

• by high levels of AMP
• high levels of pi
• high levels of fructose 2,6 bisphosphate

Question 11

What is an example of an allosteric effector for phosphofructokinase -1 ?

Answer 11

Fructose 2,6-bisphosphate

Question 12

Why are cascades important ?

Answer 12

• allow metabolic reactions to occur quickly

Question 13

What is a kinase?

Answer 13

An enzyme that catalyses the transfer of a phosphate group from ATP to a required molecule.

Question 14

What is a phosphatase

Answer 14

An enzyme that removes a phosphate group from a protein

Question 15

What is the role and importance of phosphorylation

Answer 15

• process of introducing a phosphate group to a molecule
• this in turn , activates , deactivates or modifies the function of a molecule.
• this plays an important role in protein regulation.

Question 16

What is a zymogen?

Answer 16

• also known as a proenzyme

- it is an inactive precursor of an enzyme

Question 17

Give an example of a zymogen molecule

Answer 17

• PROthrombin is the inactivated precursor enzyme for thrombin.
• PepsinoGEN is the zymogen form of the protein pepsin

Question 18

What is thrombin

Answer 18

A clotting enzyme

Question 19

Describe the structure of prothrombin

Answer 19

• • an I active form of thrombin
• the serine protease function ( the thrombin part) is contained in the C-terminal
• the two Kringle domains help keep prothrombin in the inactive form.
• Gla domains target prothrombin to appropriate sites for its activation.

Question 20

What is the role of the GLa residues on prothrombin?

Answer 20

• additional of COOH groups to glutamate residues to for, carboxyglutamate which allows interaction with sites of damage and brings together clotting factors.

Question 21

How is prothrombin converted into thrombin !

Answer 21

• enzymatic proteolytic cleavage of two sites on prothrombin which releases serine protease ( thrombin )

Question 22

What is the role of thrombin?

Answer 22

An enzyme that converts fibrinogen big molecule into insoluble fibrin fibres

Question 23

How is fibrinogen converted to form fibrin?

Answer 23

• proteolytic cleavage of the fibrinogen molecule to form fibrin which aggregates to form clots by thrombin.

Question 24

RETULATION OF CLOTTING PROCESS :

What are the two ways we can stop the clotting process ?

Answer 24

1) Digestion of clotting factors by protein C ( an inactive precursor). Protein C is only activated by thrombin binding to the endothelial receptor.
2) dilution of clotting factors by blood flow and removal by liver.

Question 25

Defects in protein C can cause what type of disease?

Answer 25

Thrombotic disease ( blood clot in a blood vessel )

Question 26

Give two another examples of how the clotting process is regulated

Answer 26

1) specific inhibitors for example antithrombin 111 (AT3) which is enhanced by heparin binding which inactivates thrombin - a major clotting factor.
2) fibrinolysis

Question 27

Fibrolysis

Answer 27

• a method of regulation used to remove a clot.
• this is where plasminogen ( an inactive precursor) is converted into plasmin. This process is activated by streptokinase and t-pa.
• plasmin enzyme then degrades fibrin clots into fibrin fragments that are later removed by the kidney/liver.