Eicosanoids Flashcards
what are eicosanoids
autocrine/paracrine hormones derived from 20-carbon unsaturated fatty acids
cleaved from membrane phospholipids
produced by all cells
not stored, rapidly degraded
what is the most abundant eicosanoid?
arachidonic acid
how long do eicosanoids last in circulation?
very short half lives- only work locally
what types of molecules are examples of eicosanoids?
prostaglandins, thromoxanes, leukotriens, lipoxins, and resolvins
how do NSAIDS work on eicosanoids
block the conversion of arachadonic acid and other fatty acids into prostaglandins and thromboxanes
what is the difference between NSAIDs and glucocortocoids
steroids block further upstream in the synthesis pathway, thus they also block the production of leukotrienes in addition to prostaglandins and thromboxanes
steroids induce synthesis of annexin 1
describe the process of platelet formation d/t vascular injury
exposed sub endothelial collagen becomes exposed and activates platelet receptors. these activate thromoxane a2 causing aggregation and vasoconstriction
in response, the surrounding epothelium secretes prostacyclin, which is antiaggregation and a vasodilator
prostacyclin
nonaggregation and vasodilation
thromboxane
aggregtation and vasoconstriction
what is the theory on why omega 3 and 6 fatty acids are beneficial
the intermediates formed while converting to prostaglandins and thromboxins do not promote platelet aggregation as easily as other fat types
getting prostaglandin I3 and thromboxane a3, which strongly inhibit aggregation and weakly cause aggregation respectively
vs
getting I2 and A2, which inhibit aggregation and cause aggregation respectively
how are omega 3 and 6 fatty acids related to TNF
the more 3.6 fatty acids you make, the less TNF you make (which is inflammatory)
what role do lipoxins, resolvins, and protectins play?
they are derived from the same precursors as prostaglandins and leukotrienes, but work towards inflammation resolution vs chronic inflammation
describe the different prostaglandins made by different cell types
platelets- thromboxin a2- (vasoconstriction/aggregation)
endothelium- PG2 (dilation, declumping)
uterus- PGF2 (contraction)
mast cells- PGD2 (chemotaxis, allergic rxns)
most cells- PGE2
describe some of the influences of PGE
IN GENERAL- CAUSES INFLAMMATION
osteoclasts- bone resorbtion
fever
ovarian cells- maturation for ovulation
neurons- enhance pain
leukotrienes and mast cells are involved in what disease?
asthma- cause constriction and inflammation in the lungs
what enzyme is key for converting fatty acid into prostaglandin?
cyclooxygenase 1 and 2 (COX 1 and 2)
why do drugs inhibit COX 2 and not 1?
COX2 is the enzyme that produces prostaglandins in response to inflammation
1 produces prostaglandins in the gut
why are NSAIDs bad for your stomach?
they inhibit both COX 1 and 2, and COX 1 is necessary in the gut
why is aspirin so good at treating vascular disease?
it inhibits COX 1 in platelets irreversibly, and platelets cannot generate new enzyme b/c they dont have a nucleus
how do prostaglandins effect the ductus arteriosus
keep it open in the fetus
describe prostaglandins effect in reproduction
stimulated by LH
induce folliucular rupture
cervical dilation
uterus contraction
corpus luteum regression
penile erection
misoprostol
analogue used in for reproductive effects
eicosanoids and the kidney
counter contraction effects of angiotensin and vasopressin
how does aspirin help w/ colon cancer?
mutant PI3-kinase- inhibiting COX2 while slow down signaling, allowing for apoptosis
leukotriene B4
chemotaxis, adhesion, vascular permeability
mast cells
lipoxygenase
converts fatty acids to leukotrienes
inhibited by lipoxygenase inhibitors
what enzyme frees arachionic acid
phospholipase a
