Lecture 11 - Enzyme Regulation Flashcards Preview

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Flashcards in Lecture 11 - Enzyme Regulation Deck (50):
1

Basic concept of zymogen

The active site is not formed correctly until there's a proteolytic cleavage at a specific activation site on the chain.

2

How is a zymogen converted into an active enzyme?

When triggered, proteolytic cleavage occurs rapidly, resulting in nearly instant activation of enzyme activity.

3

Prothrombin

The zymogen form of thrombin

4

True or false: Thrombin is a serine protease.

True

5

Where is thrombin made?

On a membrane surface

6

How many proteolytic cleavages need to be made in order to activate thrombin?

Two

7

Which cleavage activates thrombin that has been released from the membrane?

The peptide bond that allows isoleucine 16 to swing in and form a H-bond with aspartate 194 in order to put the serine 195 in the right position to be an active nucleophile

8

True or false: Activation of thrombin is reversible.

False

9

How many polypeptide chains does mature thrombin have and what kind of bond holds them together?

It has two chains (a light chain, residues 1-15, and a heavy chain, residues 16 to the end) and they are linked by a disulfide bond

10

True or false: The mature form of thrombin is water soluble.

True

11

What is the post-translational modification that is made to prothrombin that allows it to bind to the membrane?

y-carboxylation of particular glutamate residues on the N-terminus

12

Why does that modification allow prothrombin to bind to the membrane?

y-carboxy-glutamate has an extra negative charge allowing it to bind positively charged calcium ions

13

What does the binding of calcium ions allow prothrombin to do?

It exposes hydrophobic residues that can bind the membrane

14

What is the cofactor for the carboxylation of the N-terminus of prothrombin?

Vitamin K

15

What do Vitamin K antagonists do?

They interfere with the carboxylation of prothrombin, therefore it doesn't bind to membranes well and it will not form active thrombin

16

Why does prothrombin need to bind a membrane surface?

The activating protease for thrombin exists on the membrane and prothrombin must be near this enzyme in order to be activated

17

What does the activating protease for thrombin do?

It releases thrombin from the membrane surface

18

What does thrombin catalyze?

The conversion of soluble fibrinogen to insoluble fibrin that will form a blood clot

19

How do protein inhibitors work?

They bind so tightly to a given enzyme that the enzyme-inhibitor complex as a whole is degraded

20

What is an example of an enzyme-inhibitor complex?

Thrombin-antithrombin

21

What is heparin and what does it do?

It is a commonly prescribed short acting anticoagulant that promotes antithrombin-thrombin complex formation

22

What is a common vitamin K antagonist?

Warfarin

23

Elastase inhibitor

Alpha-1-antitrypsin or alpha-1-antiproteinase

24

Elastase

A protein that degrades elastin

25

Elastin

A protein in lung tissue that gives it flexibility

26

What does smoking cause?

Oxidation of alpha-1-antitrypsin

27

What are the consequences of oxidized alpha-1-antitrypsin?

It does not effectively inhibit elastase, elastase cleaves elastin without regulation and this causes lung scarring and emphysema

28

What does protein phosphorylation or dephosphorylation do?

It modifies the charge of an amino acid (like serine, threonine, or tyrosine) residue and if that residue is in or near the active site, the activity of the enzyme may be changed (increased or decreased)

29

What are the different kinds of enzyme inhibitors?

Competitive, noncompetitive, irreversible, allosteric

30

Competitive inhibitors

Binding site only; Km in presence of inhibitor will increase (1/Km will decrease); sometimes the immediate product of a reaction can compete with the substrate

31

Non-competitive inhibitors

Do not interfere with substrate binding; does not change Km, but they will decrease vmax (1/vmax will increase); interfere with catalytic machinery

32

Vmax is proportional to...

the amount of enzyme present

33

Irreversible inhibitors

Non-competitive inhibitors that bind enzymes and do not release them; this decreases the amount of enzyme present and decreases the vmax

34

True or false: Inhibitors showing a drop in vmax can be reversible or irreversible.

True

35

True or false: Changes in the substrate concentration do not change enzyme activity.

False

36

Allosteric enzymes

Usually contain multiple subunits; does not usually follow Michaelis-Menten kinetics; can define an "apparent" Km; usually have binding sites for affector molecules; often regulate a reaction pathway

37

True or false: Allosteric enzymes are very sensitive to substrate.

True

38

True or false: Allosteric enzymes are loosely regulated by substrate concentration.

False

39

Example of an allosteric enzyme

Phosphofructosekinase 1 (PFK1)

40

Allosteric enzymes are often where in a dedicated reaction pathway?

At the beginning

41

What is an allosteric activator of PFK1?

AMP

42

What is an allosteric inactivator of PFK1?

ATP

43

Why is PFK1 inhibited by high amounts of ATP?

High amounts of ATP signal that the cell is energy rich and glycolysis should not continue

44

Why is PFK1 activated by high amounts of AMP?

High amounts of AMP signal that the cell is energy poor and that glycolysis should continue

45

How many catalytic sites does PFK1 have?

Two

46

What does the Ki mean?

It marks the affinity of a substrate for an inhibitor.

47

Allosteric activators drive enzymes to what form?

Relaxed

48

Allosteric inhibitors drive enzymes to what form?

Taut

49

Where do ATP and AMP bind PFK1?

Allosteric sites

50

Feedback inhibition

Typically the product inhibiting an earlier reaction