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CMBM 3 > Eicosanoids > Flashcards

Eicosanoids Flashcards

1
Q

What are eicosanoids?

A

polyunsaturated fatty acids

  • potent mediators
  • used in immune system and vasculature
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2
Q

What are the biologic functions of eicosanoids

A 
participate in inflammatory response
-fever
-swelling
-pain
participate in smooth muscle contraction
- increase water and sodium excretion in kidney
regulate bp
can constrict or relax blood vessels
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3
Q

What best describes paracrine signaling?

A

short range cell-to-cell communication

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4
Q

What best describes autocrine signaling?

A

self signaling

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5
Q

What is the source of eicosanoids?

A

arachidonic acid from fatty acids

  • linoleate
  • essential fatty acids from plant oils
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6
Q

What is the major source for arachidonate synthesis?

A

linoleate

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7
Q

How do we make eicosadoids?

A

arachidonic acid is esterified to the phospholipid

  • phospholipase A2*** (& C)
  • triggered by infection
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8
Q

What are the 3 types of eicosanoids pathway? products of each?

A

Cyclo-oxygenase - prostaglandins, thromboxanes
Lipoxygenase - leukotrienese, HETE, lipoxins
Cytochrome P450- diHete, HETE

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9
Q

Describe the structure of Prostaglandins.

A

20 carbon atoms with a 5-C ring

Naming (PG with letter and number)

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10
Q

Describe the structure of Thromboxanes.

A

20 carbon atoms with 6-C ring

Naming (TX with letter and number)

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11
Q

**What enzyme is used to synthesize prostaglandin and thromboxanes?

A

cyclooxygenase (COX)

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12
Q

What is the key intermediate in the process of synthesis for prostaglandin/thromboxanes?

A

PGG2&raquo_space;»PGH2

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13
Q

Pair the synthase with the product that it makes.

A

TXA Synthase - platelets - Thromboxane

PGI Synthase - vascular endothelium - Prostocyclin

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14
Q

What is Prostacyclin a major modulator of?

A 
modulator of vascular tone (can be constriction or dilation) 
cAMP
platelet aggregation
leukocyte aggregation
IL-1 and IL-2
T-cell proliferation
Lymphocyte migration
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15
Q

How are thromboxanes synthesized?

A

TXA synthase

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16
Q

What is the function of Thromboxanes?

A

modulator of vasoconstriction

  • platelet aggregation
  • lymphocyte proliferation
  • bronchoconstriction
17
Q

What two forms do cyclo-oxygenase come in?

A

Cox-1 - constitutively active

Cox 2 - induced form

18
Q

Describe location of COX-1

A

widely expressed in most tissues
only form expressed in mature platelets
involved in production of PG and TX

19
Q

Decribe COX-2

A

normally low levels

  • upregulated in inflamed tissue
  • protein is upregulated by a variety of cytokines n growth factors
20
Q

What inhibits COX-1 and COX-2?

A

NSAIDs
aspirin
ibuprofen
(acetaminophen)

21
Q

How do NSAIDs work?

A

aspirin transfers an acetyl group to the enzyme which inactivates it
**irreversible
Ibuprofen and acetaminophen are ***reversible

22
Q

Low dose aspirin therapy is given to manage risk of thrombosis. Which actions of eicosanoids does aspirin interfere with to protect against thrombosis?

A

platelet aggregation

23
Q

What drugs block just COX-2?

A

serve as anti-inflammatory w/o negative GI
Celecoxib (Celebrex)
Rofecoxib (Vioxx) - removed due to increased risk of cardiovascular events

24
Q

What is glucocorticoids used for?

A

inhibit inflammation by blocking the action of phospholipase A (which make arachidonic acid)

25
Q

Describe leukotrienes.

A

expressed in leukocytes

-characteristic triene structure (3 double bonds in a series)

26
Q

Lipoxin (LX)

A

Tri-hydroxyl derivatives of arachidonic acid
-oh
made by leukocytes

27
Q

What pathway makes leukotrienes, HETE, and lipoxins?

A

lipoxygenase pathway - add peroxides

28
Q

What is the first step in conversion of arachidonic acid?

A

conversion of HPETE via lipooxygenase

29
Q

What will the unstable hydroperoxy group convert to?

A

HETE

30
Q

What are the activities of LTB4

A

vascular permeability
T-cell proliferation
leukocyte aggregation
INF-y, IL-1, IL-2

31
Q

What are the activities of LTC4

A

Bronchoconstriction
Vascular permeability
INF-y

32
Q

What makes lipoxins different?

A

OH group reductions

LX can induce chemotaxis and superoxide production in leukocytes.

33
Q

Epoxides, certain HETE and diols of HETE are generated via what pathway?

A

cytochrome p450

34
Q

What physiologic roles have been implicated with epoxides?

A

ocular
vascular
endocrine
renal

35
Q

What is the mechanism of action of eicosanoids?

A

bind to cellular receptor which can trigger activation of :
adenylyl cyclase >cAMP > protein kinase A pathway
phosphorylates CREB and initiate transcription of gene

36
Q

What are the stimulators for the pathway?

A

PGE, PGD, PGI

37
Q

What is another mechanism of action of eicosanoids?

A

cytosolic

38
Q

What type of actions can eicosanoids provoke?

A

pro and anti-inflammatory actions

39
Q

What are the clinical uses of eicosanoids?

A

suppress gastric ulceration, inhibit secretion of hydrochloric acid in the mucosal cells of the stomach
- analogs of PGE1 for sexual impotence treatment

PGE2 PGF2a - stimulate uterine muscle contraction to induce labor

PGE1 - palliative therapy in neonates with congenital heart defects

Analog of PGI - treatment of primary pulmonary hypertension

CMBM 3 (28 decks)

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