Eicosanoids

Question 1

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

Answer 1

Linoleate

Question 2

What is the source for all eicosanoids?

Answer 2

Arachidonic acid

Question 3

How is arachidonic acid obtained to make eicosanoids?

Answer 3

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

Question 4

What are eicosanoids?

Answer 4

Polysaturated fatty acids derived from the breakdown of phospholipids

Question 5

What are eicosanoid biological functions?

Answer 5

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

Question 6

What are the enzymes are involved in eicosanoid synthesis?

Answer 6

Cyclo-oxygenase, lipoxygenase, cytochrome P450

Question 7

Cyclo-oxygenase produces _____ and _____ from arachidonic acid.

Answer 7

Prostaglandins and thromboxanes

Question 8

Lipoxygenase produces these three eicosanoids.

Answer 8

Leukotrienes, HETE, lipoxins

Question 9

Cytochrome P450 produces _____ and _____.

Answer 9

diHETE and HETE

Question 10

How many carbons does the ring on prostoglandin have?

Answer 10

5

Question 11

How many carbons does the ring on thromboxane have?

Answer 11

6

Question 12

What is the synthesis enzyme of prostoglandins and thromboxanes called?

Answer 12

Cyclooxygenase

Question 13

What does cyclooxygenase do to the arachidonic acid?

Answer 13

Forms the 5 rings structure (PGG2)

Question 14

What must PGG2 do to become stable?

Answer 14

Rapidly reduced by peroxidase to form PGH2

Question 15

In vascular tissue, PGH2 becomes _____ via PGI synthase.

Answer 15

PGI2 (prostacyclin)

which modulates vascular tone and platelet aggregation

Question 16

Platelets will convert PGH2 to _____ via TXA synthase.

Answer 16

TXA2

also modulates vascular tone and platelet aggregation

Question 17

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

Answer 17

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

Question 18

What are COX 1 and 2 inhibited by?

Answer 18

Non-steroidal anti-inflammatory drugs (NSAIDS)

Aspirin, ibuprofen, acetaminophen

Question 19

What does aspirin do to COX 1 and 2?

Answer 19

Transfers an acteyl group to enzyme, irreversibly inactivating it

Question 20

Which NSAID are reversible inhibitors of COX?

Answer 20

Ibuprofen and acetaminophen

Question 21

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

Answer 21

Celecoxib (Celebrex)

Rofecoxib (Vioxx) - not in market

Question 22

What do glucocorticoids do in terms of eicosanoid synthesis?

Answer 22

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

Question 23

What are leukotrienes?

Answer 23

Molecules synthesized by leukocytes which have a triene structure

Question 24

What are lipoxins?

Answer 24

Tri-hydroxy derivatives of arachidonic acid

Question 25

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

Answer 25

arachidonic acid, HPETEs

Question 26

What will the HPETE convert to spontaneously?

Answer 26

HETE

Question 27

How is lipotoxin formed from HETEs?

Answer 27

A series of reductions

Question 28

What does lipotoxin do?

Answer 28

Function to induce chemotaxis and stimulate superoxide anion production in leukocytes

Question 29

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

Answer 29

diHETEs (because they are diols)

Question 30

What pathway are epoxides formed thorugh?

Answer 30

Cytochrome p450

Question 31

What are epoxides implicated to do?

Answer 31

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

Question 32

Prostacyclin and Thromboxane have

Answer 32

antagonistic biological effects

Question 33

Functions of PGI, E, or D

Answer 33

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

Question 34

Function of TXA2

Answer 34

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

Question 35

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

Answer 35

Platelet aggregation

Question 36

what are the functions of Lipoxins?

Answer 36

Stimulate leukocyte production of superoxides and anions | induce chemotaxis

Question 37

what are some functions of Leukotrienes?

Answer 37

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

Question 38

Role of HETE and diHETEE

Answer 38

implicated in | Ocular, vascular, endocrine and renal systems

Question 39

PGE1 and 2

Answer 39

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

Question 40

Can't get it up? Try ...

Answer 40

PGE1 just inject it into your penis works via inducing vasodilation

Question 41

Mechanisms of action of eicosaniods via

Answer 41

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

Question 42

Pro or anti inflammatory? - Leukotrienes

Answer 42

Pro

Question 43

Pro or anti inflammatory? Lipoxins

Answer 43

Pro

Question 44

Vasoconstrictive or vasodilator? Prostaglandins

Answer 44

PGF - vasoconstricts | PGI, E, D - Vasodilators

Question 45

Vasoconstrictor or vasodilator? Thromboxanes

Answer 45

Vasoconstrictor

Question 46

Induces Platelet aggregation?

Answer 46

Thromboxanes

Question 47

Broncho constrictor

Answer 47

PGF TXA LTC,LTD

Question 48

Increases vascular permeability?

Answer 48

Leukotrienes

Question 49

Stimulate uterine contraction, induce labor and control postpartum bleeding?

Answer 49

PGE2 and PGF2a

Question 50

Maintains a patent ductus arteriosus?

Answer 50

PGE1

Question 51

Analogs of PGI2 (Prostacyclin)

Answer 51

tx of primary pulmonary hypertension