Eicosanoids

Question 1

Eicosanoids

Answer 1

Synth from arachidonic acid, from inner leaflet of membrane for broad based stimuli. Function largely in defense, derived from 20C:4 FA, all cells except RBC and lymphocytes

Question 2

Eic metabolism

Answer 2

No de novo synth, need linoleic acid (18:2), released from inner leaflets by PLA2 or PLC

Question 3

Eic metab pathway

Answer 3

On paper

Question 4

Release of Arachidonate

Answer 4

Broad based stimuli (histamine, cytokines) can activate PLipase pathways to release arachidonate.

PLA2 attacks C2 ester of Phosphatidyl Choline (act = Ca; inhib = glucocorticoids)

PLC breaks Phosphatidyl inositol biphosphate from C1,C3 to 1,2 diacylglycerol. This becomes arach via DG lipase

Question 5

Arach main destinations graph

Answer 5

On paper

Question 6

Cyclooxygenase Pathway

Answer 6

Prostate and Tx. On paper.

Question 7

PGs

Answer 7

20C FA with 5 sided ring

Question 8

Txs

Answer 8

6 sided ring with central O, initiate blood clot

Question 9

Thomboxane A2

Answer 9

Created by constitutive COX1 and COX2 (inducible by cytokinesis and growth factors, inhib by ASA)

Question 10

COX and Peroxidase

Answer 10

Dimer

Reducing power from gluthathione (HMP rqrd)

Question 11

PGI2

Answer 11

Prostacyclin - produced by vasc endo cells, inhib platelet aggregation, vasodilation

Question 12

TXA2

Answer 12

Produced by platelets, activate platelet aggregation, vaso and bronchoconstriction

Question 13

COX1

Answer 13

Consitiutive, platelet agg and stomach cytoprotective. Inhib by NSAIDS

Question 14

COX2

Answer 14

inducible, inflamm and hyperalgesia. Inhib by NSAIDs, steroids

Question 15

Reason for inhib of COX

Answer 15

Excessive inflammation (COX2 = major)
NSAIDS bind at serine residue
Aspirin = uncomp inhib (irreversible)

Question 16

Prostaglandins

Answer 16

PGE and PGI = powerful vasodilators via increase cAMP, rapid inact - surgery
PGF2 = vasocons: induces contraction = norm labor, can induce abortion

Question 17

Lipoxygenase Pathway

Answer 17

Leukotriene (synth in leukocytes), HETE, Lipoxin synth. On paper

Question 18

HETE

Answer 18

mediate allergic and inflamm response

Question 19

Lipoxin

Answer 19

induces chemotaxis and stimulates Oxygen uptake in leuks

Question 20

Lipoxygenase

Answer 20

not inhibitable by NSAIDS but inhib by asthma treatment

Question 21

Leukotrienes

Answer 21

Synth in leukocytes and powerful bronchoconstrictor and SmM cons
SRS-Anaphylaxis stronger than histamine
LTC4 to LTE4 and Gluthathione to Glutamine and glycine
Pathway draw

Question 22

Blocking Eicos Synth

Answer 22

Glucocorticoids - blocks PLA2 so all
NSAIDs inhib COX (target - OH of serine: Aspirin = perm; tyl and Ibu = nonperm. Aspirin contraindicated in asthma as it directs arach acid to synth leukotrienes (vasocons)

Question 23

Eich pathway Draw

Answer 23

Draw