Brainscape's Knowledge GenomeTM

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


See full index

SMP - MNE Exam 2 > Lecture 35: Eicosanoids > Flashcards

Lecture 35: Eicosanoids Flashcards

1
Q

Other than being used to form lipid bilayers, what else are 5 important functions of lipids?

A
  1. Module activities of soluble and membrane-bound proteins
  2. Tether GPI-anchored membrane proteins (phosphatidylinositol)
  3. Act as molecular signals
  4. Have derivatives that act as intracellular second messengers in transduction pathways
  5. Potent short-lived hormone-like molecules = eicosanoids!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is an example of a lipid functioning as a molecular signal?

A

Ether-linked glycerophospholipid platelet activating

factor

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

What is an example of a lipid having derivatives that act as intracellular second messengers in transduction pathways?

A

Phosphatidylinositol (PIP2) breaking into inositol 1,4,5-triphosphate and diacylglycerol, which
then go on to regulate other enzymes

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

How is an eicosanoid formed?

A
  1. Physical damage, hormonal signal, or neuronal signal
  2. PLP A2 cleaves a polyunsaturated FA on a glycerophospholipid
  3. Polyunsaturated FA either enter cyclic (cyclooxygenase) or linear (lipoxygenase) pathway depending on what enzyme acts on it
  4. Eicosanoid is produced
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List 6 types of eicosanoids.

A
  1. Prostaglandins
  2. Thromboxanes
  3. Leukotrienes
  4. Lipoxins
  5. Hepoxilins
  6. Epi-lipoxins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the nomenclature to name eicosanoids?

A
  1. n series leukotrienes (LT)
  2. n-2 series prostaglandins (PG)
  3. n-2 series thromboxanes (TX)

n = number of unsaturated bonds in the FA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does the ω-system of naming FAs mean? Note?

A

Number after omega = number of Cs before encountering a double bond starting from the omega end of the FA (aka the terminal methyl group)

Note: count the first C included in the double bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Can mammals desaturate FAs?

A

Not very good at this, especially close to the omega end

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What organisms are good at desaturating FAs close to the ω-end? What enzymes do they use?

A

Plants using plant acyl desaturases in chloroplasts

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

Can mammals synthesize ω-3 FAs?

A

NO, we can only get them from the diet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

In what food do we find ω-3 FAs?

A

Cold water fish and flax seed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the 3 ω-3 FAs?

A
  1. alpha-linoleic acid
  2. Eicosapentaenoic acid
  3. Docosahexaenoic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the synthesis of unsaturated FAs starting with palmitic acid. Which 2 are essential for us?

A
  1. Palmitic acid - 16:0
  2. Stearate - 18:0
  3. Oleate - 18:1
  4. Linoleate - 18:2 (ESSENTIAL)
    5a. γ-linoleate - 18:3
    5b. alpha-linoleate (ESSENTIAL)
  5. Eicosatrienoate - 20:3
  6. Arachidonic acid - 20:4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is a health benefit of eating ω-3 FAs?

A

Reduced risk of heart attack

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Glycerophospholipid cleavage: phospholipase D: cleavage site? products?

A

Cleavage site = bond between polar head group and P

Products = phosphatidic acid + polar head group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Glycerophospholipid cleavage: phospholipase C: cleavage site? products?

A

Cleavage site = bond between P and O attached to C3

Products = head group-P-O2 + DAG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Glycerophospholipid cleavage: phospholipase A1: cleavage site? products?

A

Cleavage site = FA-O bond at C1

Products = FA + lysophospholipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Which glycerophospholipids are resistant to phospholipase A1? Why?

A

Ether-linked glycerophospholipids: plasmalogens and platelet activating factor because PLPAs can only cleave ester bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are 2 ether-linked glycerophospholipids? What is the difference with normal glycerophospholipids?

A
  1. Plasmalogens
  2. Platelet-activating factor
    They have an ether-linked alkane/alkene chain instead of an FA at position 1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the 2 possible head groups for plasmalogens?

A
  1. Choline

2. Ethanolamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where is the double in plasmalogens? What do we call these molecules?

A

Between C1 and C2 of the alkene chain

Vynil ethers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the composition of the platelet-activating factor. What does the position 2 portion of it allows it do to?

A
  1. Ether linked alkane chain at position 1
  2. Acetyl ester at position 2: small group allowing the molecule to circulate and be soluble in blood
  3. Phosphocholine head group at position 3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Glycerophospholipid cleavage: phospholipase A2: cleavage site? products?

A

Cleavage site = FA-O bond at C2

Products = FA + lysophospholipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What enzyme is the rate-limiting step of eicosanoid synthesis?

A

PLP A2 activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What hormones can inhibit PLP A2?

A

Glucocorticoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe the mechanism used in the cyclic pathway of eicosanoid synthesis with an ω-6 FA? Include locations

A

Step 1: SER: |protaglandin synthase=cyclooxygenase + hydroxiperoxide|: arachidonic acid => Prostaglandin H2

Step 2: Prostaglandin H2 =>

  • Prostaglandins
  • Prostacyclin synthase: Prostacyclins (PGI2)
  • Thromboxane synthase: Thromboxanes (TXA2)
27
Q

Why does aspirin have an anti-clotting effect? What is the side product?

A

INHIBITS cyclooxygenase (COX1 and 2 equally) by IRREVERSIBLE binding Ser at active site and acetylating it (side product: salicylate)

28
Q

How do NSAIDs other than aspirin work?

A

INHIBIT cyclooxygenase (COX1 and 2 equally) by REVERSIBLE binding Ser at active site

29
Q

What are the 3 isoforms of cyclooxygenase?

A
  1. COX1
  2. COX2
  3. COX3
30
Q

COX1 function? Where is it expressed? Examples?

A

Normal
housekeeping function in many tissues:

  • Limits HCl secretion in stomach to protect lining
  • Helps with blood clotting
  • Helps with vascular homeostasis
31
Q

COX2 function?

A

Involved in inflammation and pain

32
Q

What is acetaminophen best for? What does it inhibit?

A

Best for fever and pain because it inhibits COX3 and has more effects on CNS

33
Q

What difference between COX1 and 2 could potentially be used by pharma to make more targeted drugs? Which COX would you ideally want to target?

What were the names of the 2 drugs that tried to do this but had cray side effects?

A

COX1 has a little more steric hindrance for a substrate to reach the active site because it has an Ile instead of a Val in COX2

The target is COX2

Celecoxib and rofecoxib

34
Q

Why is research on eicosanoids difficult?

A

Because they are short-lived and spontaneously decompose

35
Q

What is prostacyclin’s function?

A

Very potent platelet ANTI-aggregator

36
Q

What is thromboxane’s function?

A

Very potent platelet aggregator

37
Q

What is the purpose of baby aspirin? How does it work?

A

It irreversibly inhibits COX but because vascular endothelial cells are nucleated they can generate new COX but platelets can’t (anucleated) thereby shifting the balance toward more platelet anti-aggregating activity (prostacyclins) and can prevent inappropriate platelet aggregation that could lead to thrombotic events

38
Q

Describe the mechanism used in the cyclic pathway of eicosanoid synthesis with ω-3 FAs. How does this explain why they are healthy?

A

Step 1: |protaglandin synthase=cyclooxygenase + hydroxiperoxide|: ω-3 FA => Prostaglandin H3

Step 2: Prostaglandin H3 =>

  • Prostaglandins
  • Prostacyclin synthase: Prostacyclins (PGI3)
  • Thromboxane synthase: Thromboxanes (TXA3)

Healthy because TXA3 is weaker than TXA2 thereby shifting the balance toward more platelet anti-aggregating activity (prostacyclins) and can prevent inappropriate platelet aggregation that could lead to thrombotic events

39
Q

What are the 3 forms of omega 6 eicosanoids?

A
  1. Linoleic acid
  2. Arachidonic acid
  3. gamma-linoleic
40
Q

How does PGI3 compare to PGI2?

A

Pretty much the same

41
Q

How does TXA3 compare to TXA2?

A

Pretty weak platelet activator compared to TXA2

42
Q

Why are ω-3 FAs considered heart healthy?

A

Because they are substrates for TXA3 (instead of TXA2) which is a weak platelet aggregator

43
Q

Describe the 2 mechanisms of the linear pathway of eicosanoid synthesis.

A
  1. 5-lipoxygenase + activator protein: polyunsaturated FA => leukotrienes
  2. 15-lipoxygenase + 5lipoxygenase : polyunsaturated FA => lipoxins
44
Q

What are the 2 types of leukotrienes?

A
  1. LTB4

2. Cyteinyl-leukotrienes (LTC4, LTD4, LTE4)

45
Q

What is the function of LTB4?

A

Chronic inflammation associated with atherosclerosis

46
Q

What is the function of cyteinyl-leukotrienes?

A

Inflammatory reactions of anaphylaxis

47
Q

What do some anti-asthmatic treatments use?

A

Anti-leukotriene agents that inhibit 5-lipoxygenase OR the binding of the activator protein

48
Q

What are the 2 functions of lipoxines?

A
  1. Inhibit bronchial spasms

2. Anti-inflammatory

49
Q

What triggers epi-lipoxins synthesis? What is their function?

A

Aspirin: anti-inflammatory

50
Q

What triggers resolvins and protectins synthesis? From what? What is their function?

A

Aspirin acetylation of COX2 followed by 5-lipoxygenase with 20:5 and 22:6 ω-3 FAs = resolvins/protectins: anti-inflammatory

51
Q

Where do elongation steps of FAs happen in the cell? Where do the carbons come from?

A

SER and mito

From CoA

52
Q

What is the delta nomenclature of FAs?

A

Number after delta = number of Cs before encountering a double bond starting from the delta end of the FA (aka the carboxyl group)

Note: count the first C included in the double bond

53
Q

What is the only saturation humans can do from palmitate?

A

Oleate

54
Q

What does COX and lipoxygenase do?

A

Add 2 O2

55
Q

What are thrombocytes?

A

Platelets

56
Q

Where does thromboxane synthesis occur?

A

Platelets

57
Q

What happens to TXA2 after a few seconds?

A

Spontaneously decomposes to TXB2 with water

58
Q

Where does prostacyclin synthesis occur?

A

Vascular endothelial cells

59
Q

What happens to PGI2 after a few seconds?

A

Spontaneously decomposes to PGF2 with water

60
Q

Other than through their particular eicosanoid precursor function, why else are omega-3 FAs heart healthy?

A

They reduce the amount of TAGs in the blood

61
Q

What does the number before lipoxygenases mean?

A

Where the OOH will be added

62
Q

Describe the synthesis of cysteinyl-leukotrienes and why they are named that way.

A

Polyunsaturated FA => LTA4 + glutathione (added via S of cysteine) => LTC 4 - glutamic acid => LTD4 - glycine => LTE4

63
Q

What are the 2 other NSAIDs which reversibly inhibit COX?

A
  1. Ibuprofen

2. Naproxen

SMP - MNE Exam 2 (17 decks)

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