Eicosanoids
_________ inhibits cyclooxygenase
Aspirin (the only NSAID that will covalently modify cyclooxygenase) (COX-1)
_______ is also produced in a non-enzymatic conversion of leukotriene A4
LTB4
lipoxygenase pathway produces
Leukotrienes (Think : L and L)
minor prostaglandins
PGA PGD
major prostaglandins
PGE PGF
Series 1: _______ derived from _____
PGE1 (prosta E with one double bond) eicosatrienoic acid
Series 2: derived from_______
PGE2 from arachidonic acid
Series 3 : _____ derived from _____
PGE3 derived from eicosapentaenoic acid (5 double bonds)
cyclic endoperoxide (intermediate in eicosanoid biosynthesis)
PGG PGH (very transient; just an intermediate, no other function
prostacyclin
PGI
what is required to the rate limiting step to happen?
a signal
Aspirin covalently modifies the serine residue by _________
acetylation
_________ are endogenously synthesized derivatives of arachidonic acid and may be involved in appetite regulation
anandamides
_______ is esterified to carbon 2 of the phospholipid
arachidonic acid
synthesis of leukotrienes derived from _______
arachidonic acid
acetylation of serine residue causes steric blockage of _______
arachidonic acid (substrate) (kills cyclooxygenase)
COX 1 inhibited by _____
aspirin
LTB4 is an important ______ compound
chemotactic (signaling)
TXA2 causes _____
constriction of smooth muscles
how is the structure of thromboxane different from other eicosanoids?
doesn't have a ring structure
What determines which series of eicosanoid will be synthesized?
fatty acid precursor
COX-2 is inducible by a number of factors, incluiding____
mitogens
enzyme that releases arachidonic acid from this package?
phospholipase A2 (rate limiting step of eicosanoid synthesis)
________ used in non-platelet cell _____ used in platelet cells
phospholipase A2 in non-platelet phsopholipase C in platelets
eicosanoids derived from ________
polyunsaturated fatty acids
Balance must be maintained between _______
prostacyclin and thromboxane
endothelial cells are rich in ______
prostacyclin synthesis COX2 (negative effect on platelet aggregation)
cyclooxygenase has a ______ residue in the active site
serine
COX2 inhibited by ______
steroids
SRA causes
sustained contraction of smooth muscles of the bronchii
COX 1 function
synthesizes eicosanoids needed for maintenance of cellular function
Leukotrienes C4, D4, and E4 are active components of _______
the slow reacting substance of anaphylaxis (SRA)
Storage form of eicosanoids
there is none they are synthesized upond demand; always a basal level of synthesis
platelets are rich in ________
thromboxane synthesis COX1 (platelet aggregation, vasoconstriction)
other NSAIDs inhibit cyclooxygenase by _______
tight-binding or competitive inhibition (not covalent inhibition)
2 pathways of eicosanoid synthesis after the release of arachidonic acid
1. cyclooxygenase pathway 2. lipoxygenase pathway
cyclooxygenase pathway produces
1. prostaglandins 2. thromboxanes 3. prostacyclines
How many carbons in eicosanoids?
20
2 types of cyclooxygenase
COX1 (basal; house-keeping) and COX 2 (inducal)
COX-2 is involved in the _______ resopnse
inflammatory
COX 2 primarily involved in ______
inflammatory response
Eicosanoids are not stored, but they can be packaged as ________
membrane bound phospholipids
