L11- Enzyme Regulation Flashcards
(33 cards)
What can elevated enzyme activity in blood plasma indicate?
Tissue damage.
What is a zymogen?
An inactive enzyme precursor.
How are zymogens activated?
By proteolytic cleavage.
What is the prothrombin-converting complex and what are its components?
The prothrombin-converting complex cleaves prothrombin into its active form, thrombin. It contains calcium, phospholipids, and two coagulation proteins, Factor V and Factor X.
What do Factor V and Factor X do to thrombin?
Factor V cleaves prothrombin to prethrombin. Factor X cleaves prethrombin to thrombin.
What happens to the prethrombin segment between residues 15 and 20 after prethrombin is cleaved to thrombin?
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.
Where in the cell is the mature form of thrombin generated?
On the cell membrane surface.
What class of enzymes is involved in activating prothrombin and fibrinogen in the blood clotting cascade?
Serine proteases.
Prothrombin is modified by gamma-carboxylation of which amino acid residues at its N-terminus?
Glutamate.
Why is it important for prothrombin to be gamma-carboxylated?
It allows for calcium binding, which is required to anchor prothrombin to the cell membrane.
Which enzyme catalyzes the conversion of soluble fibrinogen to insoluble fibrin?
Thrombin.
Does gamma-carboxylation of thrombin regulate enzyme activity?
No. Although gamma-carboxylation is required for formation of the active enzyme for blood coagulation, it does not directly regulate enzyme activity.
Which cofactor is required for gamma-carboxylation of prothrombin?
Vitamin K.
Name a vitamin K analogue that is used to treat thrombosis (blood clots).
Warfarin.
Warfarin is a common anti-coagulant. How does it work?
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.
Heparin is a common anti-coagulant. How does it work?
It promotes the binding of antithrombin to thrombin, thereby reducing blood clotting.
How is thrombin inactivated?
Thrombin is inactivated when a protein named antithrombin binds to its active site.
What is the role of alpha1-antitrypsin in the lungs?
It inhibits neutrophil-produced elastase in the lungs.
What is the clinical consequence of alpha1-antitrypsin deficiency with regards to the lungs?
Alpha1-antitrypsin deficiency may lead to lung destruction and emphysema.
How does cigarette smoking affect the activity of alpha1-antitrypsin?
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).
Which amino acids can typically be modified by enzymatic phosphorylation/dephosphorylation?
Serine, threonine and tyrosine.
How do competitive inhibitors block enzymatic activity?
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.
Define Ki.
Ki measures the affinity of an enzyme for a certain inhibitor. The smaller the Ki, the greater the effectiveness of the inhibitor.
Define Km.
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.
