5. Regulation of Protein Activity

Question 1

How can enzymes be regulated long term?

Answer 1

Change in rate of protein synthesis of protein degradation.

Question 2

What are isoenzymes?

Answer 2

Different forms of the same enzyme that have different kinetic properties.

Question 3

What is product inhibition?

Answer 3

When accumulation of the product of a reaction inhibits the forward reaction.

Question 4

What graph curve do allosteric regulators show between rate and substrate concentration?

Answer 4

Sigmoidal.

Question 5

What two states can multi subunit enzymes exist in?

Answer 5

T state - low affinity or R state - high affinity.

Question 6

How do allosteric activators affect enzymes?

Answer 6

Increase the proportion of enzymes in R state, so they have a higher affinity.

Question 7

What affect do allosteric inhibitors have on enzymes?

Answer 7

They increases the proportion of enzymes in the T state, so there is a lower affinity.

Question 8

How is phosphofructokinase regulated?

Answer 8

Allosterically. AMP and fructose-2,6-biphosphate activate it. ATP, citrate and H+ inhibit it.

Question 9

How do protein kinases covalently modify proteins?

Answer 9

Transfer the terminal phosphate from ATP to the -OH group of Ser, Thr or Tyr.

Question 10

How do protein phosphatases covalently modify proteins?

Answer 10

Catalyse the hydrolytic removal of phosphoryl groups from proteins.

Question 11

How are many enzymes in the digestive system activated?

Answer 11

By proteolytic cleavage.

Question 12

How is chymotrypsinogen activated?

Answer 12

By proteolytic activation. It is cleaved to n-chymotrypsin and trypsin. Then cleaved to a-chymotrypsin (active) and two dipeptides.

Question 13

How is protease activity regulated?

Answer 13

By endogenous inhibitors. a-antitrypsin inhibitor binds trypsin and stops its activity.

Question 14

What does a deficiency of a-antitrypsin cause?

Answer 14

Emphysema, the alveolar walls are destroyed by elastase.

Question 15

What is the intrinsic pathway of the blood clotting cascade?

Answer 15

Damaged epithelial lining of blood cells promotes binding of factor XI.
Factor X is activated.
Thrombin is activated.
A fibrin clot is formed.

Question 16

What is the extrinsic pathway of the blood clotting cascade?

Answer 16

Trauma releases tissue factor, factor III.
Factor X is activated.
Thrombin is activated.
A fibrin clot is formed.

Question 17

What do the Kringle prothrombin do?

Answer 17

Keep prothrombin in the inactive form.

Question 18

How is prothrombin targeted to the appropriate sites for its activation?

Answer 18

The Gla domains.

Question 19

What is the purpose of Gla residues?

Answer 19

Post translational modification of certain factors in the liver. Allows interaction with sites of damage and brings together clotting factors.

Question 20

How do prothrombin and Ca ions bind?

Answer 20

Via the Gla residues.

Question 21

How is a fibrin clot formed?

Answer 21

Thrombin cleaves fibrinopeptides A and B from the central globular domain of fibrinogen. Globular domains at the C-terminal end of the B and y chains interact with exposed sequences at the N-termini of the cleaved B and a chains to form a fibrin mesh or clot. The clot is stabilised by the formation of abide bonds between side chains of lysine and glutamine residues in different monomers. This cross linking is catalysed by transglutaminase, activated from protransgluaminase by thrombin.

Question 22

What is classic haemophilia caused by?

Answer 22

A defect in factor VIII.

Question 23

How is haemophilia treated?

Answer 23

Recombinant factor VIII.

Question 24

How is the dotting process stopped?

Answer 24

Localisation of prothrombin - the clotting factors are diluted by blood flow and removed by the liver.
Digestion by proteases - protein C degrades factors Va and VIIIa. Protein C is activated by thrombomodulin (binding of thrombin to endothelial receptor).
Specific inhibitors - antithrombin III, happiness binding enhances this.

Question 25

How is a clot broken down?

Answer 25

By fibrinolysis. Plasminogen is converted it its active form, plasmin, by streptokinase. Plasmin concerts fibrin to fibrin fragments.

Question 26

How can enzymes be regulated short term?

Answer 26

Substrate and product concentration and changes in enzyme conformation (allosteric regulation, covalent modification or proteolytic cleavage).