Eicosanoids Flashcards

0
Q

What is the purpose of the eicosanoids?

A

They are a 20 carbon structure that control/modulate several body functions by acting on extracellular surface receptors.

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1
Q

Essential fatty acids are ________ fatty acids and are the precursor for what?

A

polyunsaturated (PUFA); EFAs are the precursors of hormone-like molecules - the eicosanoids.

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2
Q

What are the parents of the omega 3 and omega 6 fatty acid families?

A

a-Linolenic (w3) and linoleic (w6)

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3
Q

What are the 4 types of eicosanoids?

A

Prostaglandins (PG), Leukotrienes (LT), Prostacyclins, and Thromboxanes (TX)

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4
Q

Which two eicosanoids have opposing actions?

A

Prostacyclins and Thromboxanes

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5
Q

What are the opposing actions of prostacyclins and thromboxanes?

A

Prostacyclins (endothelium): anti-aggregation of cells, vaso-dilation, lowers BP
Thromboxanes (platelets): aggregation of cells, vaso-constriction, raises BP

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6
Q

How do eicosanoids act as local signaling molecules?

A

They connect to G-proteins and act locally to produce local effects.

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7
Q

Which cells do the leukotrienes act upon?

A

WBCs - specifically the phagocytes: macrophages, neutrophils, and monocytes)

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8
Q

What is the parent molecule of prostaglandins?

A

Prostanoic acid

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9
Q

Bonds projecting from the ring at position 8 and 12 of prostanoic acid is in which configuration?

A

Trans

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10
Q

All natural prostaglandins have a hydroxyl at which carbon?

A

C-15

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11
Q

What does the additional letter on PG designate? (i.e. PGA)

A

Variation in ring structure and substiuents

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12
Q

What is the designation of the numerical subscript of PG?

A

Number of double bonds in the hydrocarbon chain

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13
Q

In PG what are the configurations for the following double bond locations? (13,14), (5,6), and (17, 18)

A

(13,14): Trans
(5,6): Cis
(17,18): Trans

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14
Q

True/False: Acetyl CoA can be converted to glucose…

A

FALSE!!! Acetyl CoA CANNOT be converted to glucose!

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15
Q

How are TX similar to PG?

A

TX ring structure is a 6 carbon oxy-heterocycle

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16
Q

What are LT derived from and what is their structure?

A

They are derived from HPETEs and they are an open-chain structure containing 3-5 double bonds.

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17
Q

What is the additional letter for the LT?

A

It is the specific modification of the parent chain

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18
Q

Where is arachidonic acid (AA) found?

A

It is inserted into the C-2 position of membrane phospholipids and influences membrane properties.

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19
Q

How is AA released from membrane phospholipids?

A

The major releasor of AA is phospholipase A2, which is also used to remodel the membrane. The amount of AA released is in direct proportion to how much is available.

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20
Q

Which part of the cell membrane phospholipids is inhibited by steroids?

A

Steroids inhibit the phospholipases

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21
Q

What are inhibitors of cyclooxygenase? (COX1 or COX2 inhibitors)

A

Pharm.: Aspirin, indomethacin

Natural: Ginger & Omega 3

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22
Q

What is the natural inhibitor of 5- (LOX)?

A

Ginger

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23
Q

What are natural inhibitors of Prostacyclin (PGI2)?

A

Selenium, curcumin, and zinc

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24
Q

What is a natural inhibitor of the production of both prostacyclins and TXs?

A

Zinc

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25
Q

What is a natural inhibitor of TXs?

A

Garlic and curcumin

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26
Q

What are the direct parent materials of prostacyclins and TXs?

A

Prostaglandin H2 (which derived from PGG2, from COX)

27
Q

Which material creates HPETE?

A

5-Lipoxygenase (LOX)

28
Q

HPETE creates 12-Lipoxygenase which in turn creates which two materials and what do those materials do?

A

Lipoxin A (LXA4) and Lipoxin B (LXB4): Inhibit neutrophil adhesion and chemotaxis

29
Q

HPETE creates Leukotriene A4, C4, D4, and E4. Which are the most powerful vasoconstrictors known and what do they do?

A

Leukotriene C4, D4, and E4. They are responsible for slow reacting vasoconstriction, brochospasm, and increased vascular permeability. (anaphylaxis)

30
Q

5-HPETE creates 5-HETE which is responsible for the creation of which reaction and which leukotriene?

A

Chemotaxis; leukotriene B4

31
Q

Aside from prostacyclins and TX, what does PGG (followed by PGH2) create and what are their functions?

A

PGD2 and PGE2; vasodilation and increased vascular permeability

32
Q

Cyclooxygenases (COX) initiates conversion of arachidonate and other precursors into ______ and ______.

A

PGs and TXs

33
Q

COX 1 and COX 2 are considered the ________ of all cells.

A

Housekeeper

34
Q

Lipoxygenases (LOX) converts arachidonate into _________ which is the precursor for which eicosanoids?

A

HPETEs; leukotrienes or into lipoxins

35
Q

What are the system types of COX versus LOX?

A

COX - cyclic pathway

LOX - linear pathway

36
Q

Eiscosanoids have a short half-life. How are they inactivated?

A

It is inactivated when the hydroxyl at C15 is oxidized to a ketone

37
Q

What is the anti-inflammatory action of steroids on arachidonic acid?

A

It is mediated by inducing synthesis of a protein (lipocortin) which INHIBITS Phospholipase A2.

38
Q

NSAIDS are __________ of COX. What are 2 NSAIDS and which one is reversible and which one is irreversible?

A

inhibitory; Aspirin (irreversible) and Ibuprofen (reversible)

39
Q

What is special about acetaminophen?

A

It is not an NSAID, so therefore it is not anti-inflammatory; it is a pain reliever.

40
Q

COX1 is a constitutive enzyme of what?

A

gastric mucosa, platelets, vascular endothelium and kidney; (they produce “housekeeping” prostaglandins)

41
Q

How is COX2 derived and what does it produce?

A

It is inducible; produced in response to inflammation (produces inflammatory prostaglandins)

42
Q

What are 3 stimulus for the production of arachidonic acid?

A
  1. ) Thrombin (platelet aggregation)
  2. ) Histimine
  3. ) Cytokines: IL-1, IL-6, and TNFg
43
Q

What does the number after LOX (i.e. LOX 5, LOX 12, LOX 15) designate?

A

It designates where oxygen is introduced.

44
Q

Where do we get our main sources of arachidonic acid? Why?

A

Diet; it is inefficiently synthesized from linoleic acid because delta 5 and delta 6 desaturases are slow enzymes

45
Q

The capacity for arachidonic acid synthesis is _________ with gamma-linolenic acid (GLA) in the diet.

A

greater

46
Q

Which parental eicosanoids compete for placement in membrane phospholipids?

A

Linoleic and a-linolenic compete with arachidonic acid

47
Q

What product formed from GLA is also inserted into the C2 position of membrane phospholipids?

A

Most of the DGLA

48
Q

Ultimately, which 7 products compete for placement into the membrane?

A

Oleic, linolenic, a-linoleic, GLA, DGLA, w6, and w3

49
Q

What are the 3 major types of omega-3 fatty acids in the diet?

A

a-linolenic (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)

50
Q

What is ALA converted to? What is the capacity for this pathway?

A

EPA and DHA; this pathway has a limited capacity (1-5% is actually converted)

51
Q

True/False: Omega 3 and Omega 6 fatty acids compete for placement in membrane phospholipids.

A

True

52
Q

What percent of arachidonic acid is synthesized in the body?

A

Only 5%, it is a highly inefficient system

53
Q

True/False: GLA’s are omega 3 fatty acids.

A

FALSE! They are NOT omega 3

54
Q

What are the products of DGLA?

A

Series 1 prostaglandins (PGE1) and thromboxanes (TXA1, LT3)

55
Q

Arachidonic acid is the precursor for which series eicosanoids? What processes are promoted by these?

A

Series 2 (TX2 & LT4); promotes inflammatory responses and resolution of inflammation

56
Q

What is the precursor of the series-3 eicosanoids? What are the consequences?

A

EPAs; they are less inflammatory

57
Q

What are specialized lipid pro-resolving mediators and what are they important for?

A

Lipoxins; important control elements of inflammation (repair process - recruits cells & chemical mediators)

58
Q

What is the function of lipoxins?

A

They mediate reduction in inflammation.

59
Q

Lipoxins are a product of what? Which makes them which type of omega fatty acid?

A

arachidonic acid; omega 6

60
Q

Synthesis of lipoxin epimers which physiological activity can be induced by what?

A

Aspirin

61
Q

EPA and DHA serve as precursors for what potent anti-inflammatory lipids and what are they made from?

A

Resolvins (RVs - resolves inflammation) and Protectins (PDs)
D series resolvins are made from DHA
E series resolvins are made from EPA

62
Q

Low dose aspirin induces synthesis of what?

A

Resolvins

63
Q

What tissue does protectin operate and what does it protect?

A

They operate within brain tissue and protect retinal epithelial cells

64
Q

How can specialized lipid pro-resolving mediators arise from transcellular synthesis?

A

Cell to cell interactions involving the transfer of biosynthetic intermediates.