L11- Enzyme Regulation

Question 1

What can elevated enzyme activity in blood plasma indicate?

Answer 1

Tissue damage.

Question 2

What is a zymogen?

Answer 2

An inactive enzyme precursor.

Question 3

How are zymogens activated?

Answer 3

By proteolytic cleavage.

Question 4

What is the prothrombin-converting complex and what are its components?

Answer 4

The prothrombin-converting complex cleaves prothrombin into its active form, thrombin. It contains calcium, phospholipids, and two coagulation proteins, Factor V and Factor X.

Question 5

What do Factor V and Factor X do to thrombin?

Answer 5

Factor V cleaves prothrombin to prethrombin. Factor X cleaves prethrombin to thrombin.

Question 6

What happens to the prethrombin segment between residues 15 and 20 after prethrombin is cleaved to thrombin?

Answer 6

In the active enzyme, residue 16 repositions itself. This results in the proper formation of the catalytic triad, which contains the active nucleophile residue, serine 195.

Question 7

Where in the cell is the mature form of thrombin generated?

Answer 7

On the cell membrane surface.

Question 8

What class of enzymes is involved in activating prothrombin and fibrinogen in the blood clotting cascade?

Answer 8

Serine proteases.

Question 9

Prothrombin is modified by gamma-carboxylation of which amino acid residues at its N-terminus?

Answer 9

Glutamate.

Question 10

Why is it important for prothrombin to be gamma-carboxylated?

Answer 10

It allows for calcium binding, which is required to anchor prothrombin to the cell membrane.

Question 11

Which enzyme catalyzes the conversion of soluble fibrinogen to insoluble fibrin?

Answer 11

Thrombin.

Question 12

Does gamma-carboxylation of thrombin regulate enzyme activity?

Answer 12

No. Although gamma-carboxylation is required for formation of the active enzyme for blood coagulation, it does not directly regulate enzyme activity.

Question 13

Which cofactor is required for gamma-carboxylation of prothrombin?

Answer 13

Vitamin K.

Question 14

Name a vitamin K analogue that is used to treat thrombosis (blood clots).

Answer 14

Warfarin.

Question 15

Warfarin is a common anti-coagulant. How does it work?

Answer 15

It inhibits the gamma-carboxylation reaction of prothrombin, thereby reducing the number of prothrombin molecules on the cell surface. This reduces the amount of active thrombin that can be synthesized by a cell.

Question 16

Heparin is a common anti-coagulant. How does it work?

Answer 16

It promotes the binding of antithrombin to thrombin, thereby reducing blood clotting.

Question 17

How is thrombin inactivated?

Answer 17

Thrombin is inactivated when a protein named antithrombin binds to its active site.

Question 18

What is the role of alpha1-antitrypsin in the lungs?

Answer 18

It inhibits neutrophil-produced elastase in the lungs.

Question 19

What is the clinical consequence of alpha1-antitrypsin deficiency with regards to the lungs?

Answer 19

Alpha1-antitrypsin deficiency may lead to lung destruction and emphysema.

Question 20

How does cigarette smoking affect the activity of alpha1-antitrypsin?

Answer 20

Cigarette smoke oxidizes a methionine residue on alpha1-antitrypsin that is involved in binding elastase. Oxidation of this residue prevents inhibition of elastase. (Recall that elastin is the cross-linked protein that makes lung tissue spongy).

Question 21

Which amino acids can typically be modified by enzymatic phosphorylation/dephosphorylation?

Answer 21

Serine, threonine and tyrosine.

Question 22

How do competitive inhibitors block enzymatic activity?

Answer 22

They reversibly compete with the enzyme substrate for the active site. They usually resemble the substrate in structure, so they are able to fit into the active site but cannot be acted upon by the enzyme.

Question 23

Define Ki.

Answer 23

Ki measures the affinity of an enzyme for a certain inhibitor. The smaller the Ki, the greater the effectiveness of the inhibitor.

Question 24

Define Km.

Answer 24

Km measures the affinity of an enzyme for its substrate. The smaller the Km, the greater the enzyme’s affinity for its substrate. Km is also defined as 1/2 Vmax.

Question 25

What is the effect of competitive inhibitors on Km and Vmax?

Answer 25

Competitive inhibitors increase Km but do not alter Vmax.

Question 26

What is the effect of noncompetitive inhibitors on Km and Vmax?

Answer 26

Noncompetitive inhibitors lower Vmax but do not alter Km.

Question 27

How do noncompetitive inhibitors block enzymatic activity?

Answer 27

Noncompetitive inhibitors block product formation by binding to a site other than the active site. They are able to bind the enzyme irrespective of whether or not a substrate is present.

Question 28

What are enzyme activators?

Answer 28

They are positive effectors that promote the enzyme to exist in its active form, where it is a more effective catalyst.

Question 29

True or False. Allosteric enzymes often catalyze the first step of a reaction sequence.

Answer 29

True.

Question 30

What is meant by the term ‘feedback inhibition’?

Answer 30

Feedback inhibition is a phenomenon by which the end product of a reaction or sequence of reactions inhibits the enzyme or enzymatic cascade. When sufficient product is produced, the system automatically turns itself off.

Question 31

List three common characteristics of committed steps.

Answer 31

1. They are functionally irreversible 2. They occur early in the enzymatic pathway 3. They occur in only one pathway

Question 32

Name an inhibitor of the enzyme aspartate transcarbamoylase (ATCase).

Answer 32

Cytidine triphosphate (CTP).

Question 33

Name an activator of the enzyme aspartate transcarbamoylase (ATCase).

Answer 33

Adenosine triphosphate (ATP).