Eicosanoids

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_________ 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


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