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Flashcards in Eicosanoids Deck (51):
1

What is the major essential fatty acid that synthesizes arachidonic acid?

Linoleate

2

What is the source for all eicosanoids?

Arachidonic acid

3

How is arachidonic acid obtained to make eicosanoids?

Must be released from the phospholipids it is connected to by phospholipase A2 or C

4

What are eicosanoids?

Polysaturated fatty acids derived from the breakdown of phospholipids

5

What are eicosanoid biological functions?

Participate in inflammatory response and smooth muscle contraction
Short lived - act in autocrine or paracrine fashion

6

What are the enzymes are involved in eicosanoid synthesis?

Cyclo-oxygenase, lipoxygenase, cytochrome P450

7

Cyclo-oxygenase produces _____ and _____ from arachidonic acid.

Prostaglandins and thromboxanes

8

Lipoxygenase produces these three eicosanoids.

Leukotrienes, HETE, lipoxins

9

Cytochrome P450 produces _____ and _____.

diHETE and HETE

10

How many carbons does the ring on prostoglandin have?

5

11

How many carbons does the ring on thromboxane have?

6

12

What is the synthesis enzyme of prostoglandins and thromboxanes called?

Cyclooxygenase

13

What does cyclooxygenase do to the arachidonic acid?

Forms the 5 rings structure (PGG2)

14

What must PGG2 do to become stable?

Rapidly reduced by peroxidase to form PGH2

15

In vascular tissue, PGH2 becomes _____ via PGI synthase.

PGI2 (prostacyclin)
which modulates vascular tone and platelet aggregation

16

Platelets will convert PGH2 to _____ via TXA synthase.

TXA2
also modulates vascular tone and platelet aggregation

17

What are the two forms of cyclo-oxygenase (COX)?

COX-1: constitutively active, in most tissues, expressed in mature platelets
COX-2: induced form, normal low levels but up-regulated by cytokines and growth factor in inflamed tissues

18

What are COX 1 and 2 inhibited by?

Non-steroidal anti-inflammatory drugs (NSAIDS)
Aspirin, ibuprofen, acetaminophen

19

What does aspirin do to COX 1 and 2?

Transfers an acteyl group to enzyme, irreversibly inactivating it

20

Which NSAID are reversible inhibitors of COX?

Ibuprofen and acetaminophen

21

What are the COX-2 inhibitors that don't cause GI problems or anti-platelet effects?

Celecoxib (Celebrex)
Rofecoxib (Vioxx) - not in market

22

What do glucocorticoids do in terms of eicosanoid synthesis?

Inhibits inflammation by (PG synth) by blocking the action of phospholipase A (which changes a phospholipid into a arachidonic acid)

23

What are leukotrienes?

Molecules synthesized by leukocytes which have a triene structure

24

What are lipoxins?

Tri-hydroxy derivatives of arachidonic acid

25

The lipoxygenase pathway starts with the conversion of _____ to _____ via lipoxygenase.

arachidonic acid, HPETEs

26

What will the HPETE convert to spontaneously?

HETE

27

How is lipotoxin formed from HETEs?

A series of reductions

28

What does lipotoxin do?

Function to induce chemotaxis and stimulate superoxide anion production in leukocytes

29

Epoxides are formed from certain forms of HETE called...

diHETEs (because they are diols)

30

What pathway are epoxides formed thorugh?

Cytochrome p450

31

What are epoxides implicated to do?

Not sure by probably ocular, vascular, endocrine and renal somethings and generally activate adenylyl cyclase, cAMP, or protein kinase A pathway

32

Prostacyclin and Thromboxane have

antagonistic biological effects

33

Functions of PGI, E, or D

increase vasodilation, cAMP,
decrease platelet aggregation, Leukocyte aggregation, lymphocyte migration, T cell proliferation

34

Function of TXA2

Increases vasoconstriction, platelet aggregation, lymphocyte proliferation and broncho-constriction

35

Low aspirin therapy to manage risk of thrombosis is given. What action of Eicosanoids does aspirin interfere with?

Platelet aggregation

36

what are the functions of Lipoxins?

Stimulate leukocyte production of superoxides and anions
induce chemotaxis

37

what are some functions of Leukotrienes?

increase vascular permeability, T cell proliferation, Leukocyte aggregation, Broncho constriction, release of pro-inflammatory cytokines such as IFN-y, IL-1 , IL-2

38

Role of HETE and diHETEE

implicated in
Ocular, vascular, endocrine and renal systems

39

PGE1 and 2

suppress gastric ulceration by preventing/stopping release of HCl acid from stomach mucous cells

40

Can't get it up? Try ...

PGE1
just inject it into your penis
works via inducing vasodilation

41

Mechanisms of action of eicosaniods via

activation of cAMP/PKA pathway
or increasing production of intracellular calcium

42

Pro or anti inflammatory? - Leukotrienes

Pro

43

Pro or anti inflammatory? Lipoxins

Pro

44

Vasoconstrictive or vasodilator? Prostaglandins

PGF - vasoconstricts
PGI, E, D - Vasodilators

45

Vasoconstrictor or vasodilator? Thromboxanes

Vasoconstrictor

46

Induces Platelet aggregation?

Thromboxanes

47

Broncho constrictor

PGF
TXA
LTC,LTD

48

Increases vascular permeability?

Leukotrienes

49

Stimulate uterine contraction, induce labor and control postpartum bleeding?

PGE2 and PGF2a

50

Maintains a patent ductus arteriosus?

PGE1

51

Analogs of PGI2 (Prostacyclin)

tx of primary pulmonary hypertension