Flashcards in Enzyme Regulation Deck (21):
1
enzymes as biomarkers
-enzymes are expressed only in certain tissues thus the appearance of these enzymes in the blood is a sign of tissue damage
2
zymogens
-inactive forms of enzymes (precursor)
-many enzymes are produced in a zymogen state and then upon proteolytic cleavage, the active site is made available and the enzyme becomes catalytic
3
overview of blood clotting cascade
-damaged molecules activate enzymes in a cascade which progressively increases the number of components involved
4
activation of prothrombin
-prothrombin, which resides on the membrane of endothelial cells, is activated into thrombin
-thrombin is released into the blood and converts fibrinogen into fibrin
-firbrin then becomes cross-linked in order to form a blood clot
5
Thrombin
-protein specificis
-active site
-serine protease
-H bonding between Ile16 and COO- of Asp194 is what primes Thrombin for catalysis
-is made on the membrane surface
6
prothrombin
-reside on the membrane due to a gama carboxylation modification on the N term
-this is also made possible by the presence of Ca, which when bound to prothrombin, exposes a hydorphobic region for interaction with the membrane
7
Vitamin K and caboxylase
-viatmin k antagonists
-
-these molecules facilitate the conversion of the glutamate residue on prothrombin to a gama-carboxyglutamate residue in order for it to associate with the membrane
-viatmin K antagonists interfere with the carboxylation reaction
-poorly carboxylated prothrombin and its activating enzyme do not bind well to a membrane surface thus reducing activation and clotting
8
protein inhibitors of enzymes
-example
-these bind so tightly that the enzyme-inhibitor complex is degraded as a whole
-the inhibition is irreversible
-an example would be antithrombin and thrombin
9
heparin
-short acting anticoagulant which promotes antithrombin-thrombin formation
10
inflammatory response of neutrophils in the lungs
-once a particle is recognized, they will release elastase which is meant to break down the cell wall of gram neg bacteria
-elastase is normally inhibitted in the tissue by alpha1-antitrypsin or alpha1-antiproteinase
-if this enzyme is defective you will have unregulated elastase activity which destroys the elastin in the lung tissue leading to emphysema
11
smoking and alpha1-antitrypsine
-there are many oxidants in cigarette smoke which convert a methionine residue to methionine sulfoxide
-therefore it can not due its job of inhibiting elastase and a smoker will develop emphysema
12
protein phosphorylation
-phosphorylation or dephosphorylation modifies the charge of an amino acid residue
-if the serine, threonin, or tyrosine is in the active site, the activity of the enzyme will be changed
-overall, there switch from a hydroxyl group to a phosphate
13
competitive inhibitors
-bind to the active site
-Km will be increased
-Vmax remains the same, just takes more substrate to reach
14
noncompetitive inhibitors
-interferes with catalytic machinery only
-Km remains the same
-Vmax is diminished
15
irreversible inhibitors
-kill the enzyme
16
allosteric effectors
-inhibitors or activators that do not bind to the active site
17
Ki
inversely related to the affinity constant. The lower the Ki, the tighter it binds
18
DIFP
-irreversible inhibitor of serine proteases
-only one serine out of many are modified
-inhibition of the serine protease, acetylcholine esterae results in improper nerve function by reducing the enzyme velocity
19
allosteric enzyme substrate sensitivity
-usually more sensitive to substrate and they have a sigmoidal velocity to substrate plotr (can not determine exact Km)
-usually contain multiple subunits
-usually have binding site for affector molecules
-often regulate a reaction pathway
20
where in the pathway are allosteric enzymes typically found
-at the beginning of the pathway
-it may be allosterically controlled (inhibited) by a product down the line in the pathway.
21