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Haemostasis & Thrombosis > Mechanisms of Inhibiton > Flashcards

Mechanisms of Inhibiton Flashcards

1
Q

What inhibitors do endothelial cells release?

A

NO and PGI2

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2
Q

What enzyme degrades ADP?

A

Ecto-ADPase (CD39)

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3
Q

What enzymes synthesize cAMP & cGMP?

A

AC - cAMP
GC - cGMP

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4
Q

What do AC and GC use to make cAMP & cGMP?

A

AC uses ATP
GC uses GTP

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5
Q

What enzyme degrades cAMP & cGMP?

A

Phosphodiesterase

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6
Q

What activities determine cyclic nucleotide levels?

A

Balance of AC/GC and PDE

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7
Q

What signalling is adenylyl cyclase linked to?

A

GPCR signalling

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8
Q

What does NO allow for with guanylyl cyclase?

A

Skips ligand receptor step - enters cell directly

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9
Q

What is AC stimulated by?

A

Gs-G-protein after binding to PGI2

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10
Q

What is GC stimulated by?

A

NO

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11
Q

Which PDE is specific for cAMP?

A

PDE 2 & 3

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12
Q

Which PDE is cGMP specific?

A

PDE5

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13
Q

How does cGMP elevate cAMP levels?

A

Inhibits PDE3 - allows more cAMP to survive

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14
Q

How does cGMP decrease cGMP levels (-ve feedback loop)?

A

Stimulates PDE5

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15
Q

What do mutations in sGC lead to?

A

Reduced cGMP production -> increases risk for myocardial infarction & coronary artery disease

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16
Q

What are the targets for cAMP?

A

PKA

17
Q

What are the targets for cGMP?

A

PKG

18
Q

What are AKAP and GKAP?

A

PKA/PKG anchoring proteins that direct PKA & PKG to specific subcellular compartments

19
Q

What is the role of PKA & PKG?

A

Phosphorylation of multiple substrate proteins -> regulation of signaling & actin dynamics -> platelet inhibition

20
Q

What do the inhibitory pathways not interact with?

A

Integrin or granule release

21
Q

What do PKA & PKG add to serine & threonine residues?

A

-vely charged phosphate groups to substrate proteins

22
Q

What does phosphate addition cause?

A

changes the function of substrate proteins by facilitating and/or blocking binding of regulatory proteins

23
Q

What is the inactive form of RAP?

A

RAPGDP
RAP1GAP2 turns RAP off

24
Q

What protein turns Gq signalling off?

A

RGS18

25
Q

Which protein inhibits RGS18 & RAP1GAP2 during platelet activation?

A

14-3-3

26
Q

What does phosphorylation of RGS18 & RAP1GAP2 cause?

A

14-3-3 detaches and RGS18 & RAP1GAP2 becomes active

27
Q

What does the phosphorylation of CD-GEF1 cause?

A

Blocks GEF activity -> RAP1 not turned on

28
Q

How does ADP help block inhibitory pathways during platelet activation?

A

By stopping cAMP synthesis

29
Q

What is the mechanism that ADP uses to reduce cAMP levels

A

P2Y12 receptor for ADP is coupled to Gi
Gi inhibits adenylate cyclase
cAMP levels are reduced

30
Q

What antibody is used as a marker for P2Y12 activity?

A

Antibody-based detection of VASP phosphorylation

31
Q
A

Haemostasis & Thrombosis (17 decks)

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