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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

phosphofructokinase

-this is an example of an allosteric enzyme
-turns fructose-6-P into fructose-1,6-bisP
-this is capable of making ATP
-high AMP signals that the cell is energy poor, turning this process on
-high levels of ATP inhibit this process by ATP allosterically binding to this enzyme