Eicosanoids Flashcards
Eicosanoids
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
Eic metabolism
No de novo synth, need linoleic acid (18:2), released from inner leaflets by PLA2 or PLC
Eic metab pathway
On paper
Release of Arachidonate
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
Arach main destinations graph
On paper
Cyclooxygenase Pathway
Prostate and Tx. On paper.
PGs
20C FA with 5 sided ring
Txs
6 sided ring with central O, initiate blood clot
Thomboxane A2
Created by constitutive COX1 and COX2 (inducible by cytokinesis and growth factors, inhib by ASA)
COX and Peroxidase
Dimer
Reducing power from gluthathione (HMP rqrd)
PGI2
Prostacyclin - produced by vasc endo cells, inhib platelet aggregation, vasodilation
TXA2
Produced by platelets, activate platelet aggregation, vaso and bronchoconstriction
COX1
Consitiutive, platelet agg and stomach cytoprotective. Inhib by NSAIDS
COX2
inducible, inflamm and hyperalgesia. Inhib by NSAIDs, steroids
Reason for inhib of COX
Excessive inflammation (COX2 = major) NSAIDS bind at serine residue Aspirin = uncomp inhib (irreversible)
Prostaglandins
PGE and PGI = powerful vasodilators via increase cAMP, rapid inact - surgery
PGF2 = vasocons: induces contraction = norm labor, can induce abortion
Lipoxygenase Pathway
Leukotriene (synth in leukocytes), HETE, Lipoxin synth. On paper
HETE
mediate allergic and inflamm response
Lipoxin
induces chemotaxis and stimulates Oxygen uptake in leuks
Lipoxygenase
not inhibitable by NSAIDS but inhib by asthma treatment
Leukotrienes
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
Blocking Eicos Synth
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)
Eich pathway Draw
Draw
