Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

B32PAI - Pharmacology & Therapeutics > Arachidonic Acid Metabolism > Flashcards

Arachidonic Acid Metabolism Flashcards

1
Q

What is the COX enzyme responsible for?

A
  • One step in the conversion of membrane phospholipids (substrate) into prostanoids (e.g. prostaglandins/thromboxane)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the first step in prostaglandin synthesis?

A
  • Membrane phospholipid is cleaved to release arachidonic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What enzyme catalyses the release of AA from membrane phospholipid?

A
  • phospholipase A2 (PLA2)

cPLA2 is most important

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the key structural features of cPLA2 that allow it to carry out catalysis?

What intermediate is formed?

A
  • Ser228 and Asp 549 form the catalytic diad (with a bit of shit joining them in the middle); they hydrolyse the phospholipid
  • Acyl intermediate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is the enzyme cPLA2 regulated acutely?

A
  • Upon agonist stimulation
  • Activates intracellular pathways signalling to PLC and activating IP3
  • Leads to Ca2+ being released from the ER
  • Allows cPLA2 to move from cytosol to membrane to bind
  • Meanwhile ERK (extracellular regulated kinase) has also been activated by agonist stimulation
  • Phosphorylates cPLA2 to active form allowing it to bind/catalyse
  • Thus when Ca2+ binds to the C2 domain of cPLA2, it facilitates membrane binding and then the works
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can cPLA2 mRNA expression be upregulated?

A
  • Inflammatory mediators can upregulate cPLA2 expression; thus there is more cPLA2 inside the cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How can cPLA2 mRNA expression be downregulated?

A
  • Glucocorticoids downregulate expression (steroidal anti-inflammatory); they can induce a repressor protein (S100)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the second step of prostaglandin synthesis following cPLA2 activity to produce AA?

A
  • Prostaglandin H2 synthase (COX-enzyme) converts AA to Prostaglandin H2 (via a PGG2 intermediate)
  • Cyclooxygenase activity to generate PGG2
  • Then peroxidase activity to generate PGH2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where is the COX enzyme (Prostaglandin H2 synthase) found in the cell?

A
  • Bound to ER (endoplasmic reticulum) and nuclear envelopes

- In close vicinity to PLA2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the structural features of the COX enzyme?

A
  • COX-1/COX-2 isoforms (both homodimers)
  • EGF domain; responsible for dimerisatoin
  • Contains a haem group
  • Has an AA channel; AA enters via channel and positions itself at key Tyr385 residue; PGH2 formed there
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When are COX-1 and 2 respectively expressed?

A
  • COX-1; expressed all the the time in most tissues ‘housekeeping’
  • COX-2 regulated at mRNA level
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

When is COX-2 expressed?

A
  • Induced by growth factors and inflammatory mediators (inflammatory soup) such as IL-1, TNF-α, LPS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What cells express COX-2?

A

Many cells including immune cells, endothelial cells lining the blood vessel wall and fibroblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does COX’s proximity to cPLA2 on the membrane/nuclear envelope confer?

A
  • As soon as AA is generated by cPLA2 it can go immediately to COX to generate PGH2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the third stop in the prostaglandin synthesis pathway after PGH2 is generated, and what is produced?

A

Prostanoid synthesis by synthases, converts PGH2 into respective prostanoids:

  • PGD2 (prostaglandin D2)
  • PGDF2α (prostaglandin F)
  • TXA2 (thromboxane)
  • PGI2 (prostacyclin)
  • PGE2 (involved in sensitisation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where is PGD2 synthase localised?

A

Mast cells

17
Q

Where is PGE2 synthase localised?

A

Macrophages, fibroblasts, endothelial cells

18
Q

Where is PGF2α synthase localised?

A

Uterus

19
Q

Where is PGI2 synthase localised?

A

Endothelial cells

20
Q

Where is TxA2 synthase localised?

A

Platelets

21
Q

What is the next step in the prostaglandin synthesis pathway after they have been made?

A

Transport:

  • PGs synthesised inside the cell (cPLA2 and COX inside the cell)
  • ABC transporters transport PGs across the plasma membrane into the extracellular space and act as signalling molecules respectively
22
Q

What is the final step in the prostanoid synthesis pathway?

A
  • Prostanoids bind to their respective receptors
23
Q

What are the prostanoid receptors for PGE2 (and which is most relevant to pain)?

A
  • EP1
  • EP2 (localised on sufurce of nociceptor; implemented in sensitisation)
  • EP3
  • EP4
24
Q

What are the main effects that PGD2 bring about at DP1, 2?

A
  • Vasodilation

- Inhibition of platelet aggregation

25
Q

What are the main effects that PGE2 bring about at EP1-4?

A
  • Vasodilation
  • Hyperalgesia (sensitisation)
  • Inhibition of gastric acid secretion
26
Q

What are the main effects that PGF2α bring about at FP?

A

Smooth muscle contraction

27
Q

What are the main effects that prostacyclin (PGI2) bring about at IP?

A
  • Vasodilation

- Inhibition of platelet aggregation

28
Q

What are the main effects that TXA2 (thromboxane) bring about at TP?

A
  • Vasoconstriction

- Platelet aggregation

B32PAI - Pharmacology & Therapeutics (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions