Eicosanoids
C2, PLA2 (phospholipase A2)
Arachidonic acid resides at the _____ position of membrane PLs. Released from there by activation of _____.
serine
Aspirin acetylates a _____ residue to the active sites of COX1 and 2.
TXA2, prostacyclin (PGI2)
Aspirin reduces activity of _____ but does not have much effect on _____ because endothelial cells can make new COX1/2, which decreases platelet aggregation
Joints, skin, eyes
Eicosanoids mostly produce inflammatory responses on these 3 body areas:
5-LOX
In leukotriene synthesis, arachidonic acid ---> HPETE via
Prostaglandin
Induction of COX2 leads to _____ synthesis, which increases pain, heat, swelling, and fever.
Glutamate
LC4 --> LTD4 when _____ is removed.
Glutathione
LTA4 gives rise to LTC4 by addition of _____
Bronchoconstriction (also vasoconstriction and lung edema)
LTC --> LTE increase vascular permeability (for allergy/hypersensitivity reactions) but can lead to severe _____
Glycine
LTD4 ---> LTE4 when _____ is removed.
2
Linoleic acid is a _____ series PUFA.
3
Linolenic acid is a _____ series PUFA.
alpha-linolenic (omega 3)
Minor eicosanoids are derived from _____ obtained in diet.
PGH2 synthase
PGH2 (parent prostaglandin) is synthesized from PGG2 by _____
prostaglandins, thromboxanes
PGH2 gives rise to _____ and ____
Cyclooxygenase, peroxidase
PGH2 has these 2 activities _____ (rate limiting) and _____.
EPA
TXA3 is less potent than TXA2, so increasing amounts of _____ instead of arachidonic acid promotes better vascular health (less risk for clots). This molecule will be released by activation of PLA2 instead of arachidonic acid.
Cyclooxygenase (COX1 and COX2)
The rate-limiting enzyme in prostaglandin and thromboxane synthesis is _____
Thromboxane A2 (TXA2), prostacyclin (PGI2)
These 2 molecules have opposite affects on platelet aggregation/BVs.
LTC --> LTF
These 4 molecules are cysteinyl leukotrienes
EPA (eicosapentenoic acid)
This PUFA = 20:5
LTA4
This is the parent leukotriene
PLA2 (phospholipase A2)
____ cleaves PIP2 into arachidonic acid and Lyso-PIP2.
Aspirin
____ irreversibly inhibits COX1 and COX2, decreasing synthesis of prostaglandins and thromboxanes.
Asthma
____ is treated by inhibiting leukotriene synthesis or leukotriene receptors.
TXA2
____ promotes platelet aggregation, vasoconstriction, and contraction of SM.
Prostacyclin (PGI2)
____ promotes vasodilation and inhibits platelet aggregation.
Cysteinyl-leukotrienes
_____ are relased during anaphylaxis and are components of the slow-reacting substance of anaphylaxis.
Cortisol
_____ inhibits activation PLA2, preventing the release of arachnoid acid and the formation of ALL eicosanoids (prevent inflammation)
LTB
_____ is a chemoattractant and is not directly involved in allergic/hypersensitivity reactions.
COX1, COX2
_____ is constitutively active while _____ has to be induced.
NSAIDs (non-steroidal)
_____ reduce inflammation by inhibiting BOTH COX1 and COX2, resulting in reduced production of prostaglandins and thromboxanes.
Linoleic acid (18:2)
Arachidonic acid (20:4) is derived from _____, an omega 3 FA.
cAMP, IC Ca
All eicosanoids function through specific GPCR pathways, leading to either increased _____ or increased _____.
RBCs
All mammalian cells except _____ synthesize eicosanoids.
PLA2, COX2
Glucocorticoids can inhibit _____ and _____