Enzyme Regulation

Question 1

enzymes as biomarkers

Answer 1

-enzymes are expressed only in certain tissues thus the appearance of these enzymes in the blood is a sign of tissue damage

Question 2

zymogens

Answer 2

• 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

Question 3

overview of blood clotting cascade

Answer 3

-damaged molecules activate enzymes in a cascade which progressively increases the number of components involved

Question 4

activation of prothrombin

Answer 4

• 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

Question 5

Thrombin

• protein specificis
• active site

Answer 5

• serine protease
• H bonding between Ile16 and COO- of Asp194 is what primes Thrombin for catalysis
• is made on the membrane surface

Question 6

prothrombin

Answer 6

• 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

Question 7

Vitamin K and caboxylase
-viatmin k antagonists
-

Answer 7

• 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

Question 8

protein inhibitors of enzymes

-example

Answer 8

• 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

Question 9

heparin

Answer 9

-short acting anticoagulant which promotes antithrombin-thrombin formation

Question 10

inflammatory response of neutrophils in the lungs

Answer 10

• 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

Question 11

smoking and alpha1-antitrypsine

Answer 11

• 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

Question 12

protein phosphorylation

Answer 12

• 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

Question 13

competitive inhibitors

Answer 13

• bind to the active site
• Km will be increased
• Vmax remains the same, just takes more substrate to reach

Question 14

noncompetitive inhibitors

Answer 14

• interferes with catalytic machinery only
• Km remains the same
• Vmax is diminished

Question 15

irreversible inhibitors

Answer 15

-kill the enzyme

Question 16

allosteric effectors

Answer 16

-inhibitors or activators that do not bind to the active site

Question 17

Ki

Answer 17

inversely related to the affinity constant. The lower the Ki, the tighter it binds

Question 18

DIFP

Answer 18

• 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

Question 19

allosteric enzyme substrate sensitivity

Answer 19

• 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

Question 20

where in the pathway are allosteric enzymes typically found

Answer 20

• at the beginning of the pathway

- it may be allosterically controlled (inhibited) by a product down the line in the pathway.

Question 21

phosphofructokinase

Answer 21

• 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