Regulation Of Protein Activity

Question 1

Long term regulation

Answer 1

change in the rate of protein synthesis

change in the rate of protein degradation

Question 2

Isoezymes

Answer 2

Different forms of the same enzymes that often have different kinetic properties

Question 3

Product inhibition

Answer 3

Accumulation of a product inhibits its own production
e.g. Glucose-6-phosphate inhibits hexokinase activity - important in controlling the rate at which different tissues metabolise glucose

Question 4

Allosteric regulation

Answer 4

Allosteric activators increase the proportion of enzymes in the R state (high affinity)
Allosteric inhibitors increase the proportion of enzymes in the T state (low affinity)

Phosphofructokinase is allosterically regulated and sets the pace for glycolysis (activated by AMP, inhibited by ATP)

Question 5

Covalent modification - phosphorylation

Answer 5

Protein kinases - transfer of terminal phosphate from ATP to -OH group of Ser, Thr, Tyr (large negative charge)
Protein phosphatase - catalyses the hydrolytic removal of phosphoryl groups from proteins

Question 6

Enzyme cascade

Answer 6

Enzymes activate enzymes - the number of affected molecules increases geometrically. Amplifies the initial signal by several orders of magnitude within a few milliseconds.

Question 7

Specific proteolytic cleavage

Answer 7

Cut at specific amino acids
Don’t want active enzymes, that are usually secreted, inside of cells so are made in the inactive form - zymogens - they are then cleaved to an active form when they are needed

Question 8

Rate of protein synthesis

Answer 8

The body responds to an increase in metabolites by making more enzymes - happens with alcohol - body responds to high alcohol consumption by making more enzyme to break down the alcohol

Question 9

The blood clotting cascade

allows the formation of a clot form activation of very small amounts of the initial factor

Answer 9

Extrinsic pathway - (simulates the intrinsic pathway) activated by trauma
Factor X activation (common endpoint for both pathways
Leads to thrombin activation (Gla domains)
Which leads to the formation of a fibril clot
+ve Ca2+ pulls the clotting factors out of the blood since they are -ve (localises the clot)

Question 10

Extrinsic pathway

due to vascular damage

Answer 10

Tissue factor III activates Tissue factor VII which activates Factor X
Thrombin activates the formation of the Fibrin clot
(This then stimulates the intrinsic pathway)

Question 11

Intrinsic Pathway

Answer 11

Factor XI activates Factor IV which then activates Factor X

Leads to the activation of Thrombin and then the formation of the Fibrin clot

Question 12

Formation of a Fibrin Clot

Answer 12

Thrombin cleaves fibrinopeptides A and B from the central globular domain of fibrinogen.
Globular domains at the C-terminal ends of the beta and gamma.chains interact with exposed sequences at the N-terminal of the cleaves beta and alpha chains to form a fibrin mesh or clot.
The newly formed clot is stabilised by the formation of a ice bonds.

Question 13

Haemophilia

Answer 13

Defect in factor VIII

Question 14

Stopping the clotting process

Answer 14

Dilution of clotting factors by blood flow and by removal by liver
Digestion by proteases
Specific inhibitors - antithrombin III
Fibrinolytic - breaks up of the clot after the tissue has been repaired (can be stimulated by streptokinase)

Question 15

Short term regulation

Answer 15

substrate and product concentration 
change in enzyme conformation 
~ allosteric regulation 
~ covalent modification 
~ proteolytic cleavage