Session 11: Regulation of Protein Function Flashcards Preview

MCBG > Session 11: Regulation of Protein Function > Flashcards

Flashcards in Session 11: Regulation of Protein Function Deck (58):
1

What are the four short-term ways by which enzyme activity can be regulated?

Substrate and product concentration
Allosteric regulation
Covalent modification
Proteolytic cleavage

2

What are the two long-term ways by which enzyme activity can be regulated?

Change in the rate of protein synthesis
Change in the rate of protein degradation

3

Which is the easiest way to control the activity of an enzyme?

Changing substrate and product concentration

4

What are isoenzymes?

Different forms of the same enzyme that have different kinetic properties

5

What is product inhibition?

When accumulation of the product of a reaction inhibits the forward reaction

6

Give an example of product inhibition

Glucose-6-phosphate inhibiting hexokinase activity

7

Allosteric enzymes have what feature in regard to their subunits?

They are multiple subunits

8

What kind of curve do allosteric enzymes show in a relationship between rate and substrate concentration?

Sigmoidal curve

9

Allosteric enzymes can exist in two forms, what are they? How does this form relate to their affinity?

T state "Tense" - low affinity
R state "Relaxed" - high affinity

10

Allosteric activators increase the proportion of enzyme in what state?

R "relaxed" state

11

Allosteric inhibitors increase the proportion of enzyme in what state?

T "tense" state

12

Which enzyme responsible for setting the pace of glycolysis is allosterically activated?

Phosphofructokinase (PFK)

13

What are the two allosteric activators of PFK?

AMP
Fructose-2,6,-bisphosphate

14

What are the three allosteric inhibitors of PFK?

ATP
Citrate
Hydrogen ions

15

What is allostery?

Regulation of a protein by the binding of an allosteric molecule at a size other than they enzymes active site

16

How do allosteric effectors work?

They bind to an allosteric site and change the conformation of the protein which changes to shape of the active site and therefore inhibits or enhances the substance

17

Give three examples of a covalent modification of proteins

Phosphorylation
Acetylation
Sulfation
Ubiquitination

18

Which of the methods of covalent modification of proteins is most important in terms of regulation?

Phosphorylation

19

How does phosphorylation work?

Protein kinases can transfer phosphate from ATP to the -OH (hydroxyl) group of Serine, Theronine and Tyrosine residues to produce a phosphorylated protein

20

What group of molecules are able to reverse the affects of kinases? How do they do this?

Phosphatases
By catalysing the hydrolytic removal of the phosphoryl group from proteins

21

Phosphate is transferred onto what structural aspect of proteins?

-OH (hydroxyl group)

22

Why is protein phosphorylation so effective? (5things)

Hydrogen bonds can be made by the phosphoryl group
Amplification of the signal
Rate of phosphorylation/dephosphorylation can be adjusted
ATP linked to the energy status of the cell
Negative charges added (2)- changes the conformation

23

Using an example, explain what is meant by reciprocal regulation?

In glycolysis, breakdown of glycogen is induced by the same signals that inhibit the synthesis of glycogen

24

Why are enzyme cascades important?

They allow amplification of initial signal by several orders of magnitude within a few milliseconds

25

What is a kinase?

An enzyme that add phosphates to proteins

26

What is a phosphatase?

An enzyme that removes phosphates from proteins

27

Why does phosphorylation have an effect?

Changes the conformation of the protein which leads to the recruitment and interaction of the protein with different molecules and changes its activity

28

What is a zymogen?

An inactive enzyme precursor

29

Which processes in the body use zymogens?

Digestion
Blood clotting
Development
Synthesis of protein hormones
Apoptosis

30

Give some examples of zymogens used in digestion? What are they activated to form?

Pepsinogen is activated to give pepsin
Trypsinogen is activated to give trypsin

31

Pancreatic proteases such as elastase have a wide range of specificities, their activation is controlled by what?

Trypsin

32

How are pancreatic proteases turned-off once activated by trypsin?

Pancreatic trypsin inhibitor: alpha1-antitrypsin binds to trypsin and stops its activity

33

A deficiency in alpha1-antitrypsin can cause what disease? What causes this?

Emphysema
The proteases are not controlled, alveolar walls are destroyed by elastase

34

What causes the long-term regulation of proteins by changing the rate of protein synthesis?

Enzyme induction or repression

35

What causes the long-term regulation of proteins by changing in rate of protein degradation?

Ubiquitin-proteasome pathway

36

The protease function (thrombin part) is contained in the C- terminal or the N-terminal domain of prothrombin?

C-terminal

37

What is the importance of the clotting cascade?

It allows the formation of a vital clot from the activation of small amounts of initial factor through amplification

38

The extrinsic pathway of the clotting cascade is caused by what?

Damage to the membrane which exposes extracellular domain of tissue (factor III)

39

The intrinsic pathway of the clotting cascade is caused by what?

Membrane damage that leads to factor IX and X being targeted to the membrane at damage site by Gla domains which are attracted to positively charged calcium ions

40

Where do post-translational modification of clotting factors II, IV, IX and X occur?

In the liver

41

How is carboxyglutamate (Gla) formed?

The addition of COOH to glutamate residues

42

The carboxylation of glutamate to form Gla residues in the liver is dependent on what?

Vitamin K

43

What is the name of the domains that help to keep prothrombin in the inactive form?

Kringle domains

44

The Gla domain is responsible for what?

The targeting of clotting factors to sites of damage

45

Why is the calcium-binding region of prothrombin so important?

It means that only prothrombin next to the site of damage will be activated and clots will be localised to only this site

46

Describe the important structural features of fibrinogen

It has 3 globular domains linked by rod-like alpha helices
2 sets of tripeptides (alpha,beta,gamma) are joined by N-terminal disulphide bonds

47

What feature of fibrinogen prevents the aggregation of the molecules?

The N-terminal regions of alpha and beta chains are highly negative so they cannot come together

48

How does thrombin cause the activation of fibrinogen into fibrin?

Cleaves off the fibrinopeptides at the N-terminal regions, they can then interact with the globular domains to for a fibrin mesh or clot

49

The initial clot that is formed prior to cross-linking is known as what? What do we call this following formation of cross-links?

"Soft-clot" initially
Then forms a "hard-clot"

50

Classic haemophilia is cause by a defect in what?

Clotting factor VIII

51

Clotting factor VIII is an example of a what?

Allosteric activator

52

What does factor VIII do?

Stimulates he activity of factor IXa (A serine protease)

53

The intrinsic pathway is maintained by what, meaning that it doesn't need to extrinsic pathway to maintain the clotting process?

Positive feedback to members of the upstream pathway

54

What three methods are needed to regulate the clotting process?

Localisation of (pro)thrombin
Digestion of proteases
Specific inhibitors

55

Which molecule is responsible for breaking up clotting factors in order to inactivate them?

Protein C

56

What are some examples of regulators of clotting?

Antithrombin III (AT3)
Plasminogen

57

Plasminogen is activated by what to produce its activate form plasmin?

Tissue plasminogen activator (t-PA)
Streptokinase

58

Plasmin does what?

Breaks up fibrin clot into fibrin fragments