Eicosanoids Flashcards
What are eicosanoids synthesized from? via reduction or oxidation?
arachidonic acid via oxidation
What are the three classes of eicosanoids?
prostaglandins, thromboxanes, leukotriends
Are Eicosanoids hydrophobic or hydrophilic? What systems are they involved in?
hydrophobic, involved in autocrine, paracrine, and can be endocrine
What are eicosanoids important in?
inflammation
What would you target to prevent arachidonic acid formation?
Phospholipase A2 or C
What is arachodinic acid formed from?
The cleaving of the glycerol backbone off of diacylglercol or phospholipid
What can arachoidonic acid be turned into? Which is more common?
PGH2 or Luekotriens; PGH2 is more common
What can we target to inhibit prostaglandins?
PTGS1 or 2 (or cox-1 or 2)
What can we target to inhibit leukotriends?
leukotriens
What turns arachondic acid into PGH2?
PTGS1 or PTGS2
What turns arachadonic acid into leukotriens?
LOX-5
What the four targeted tissue for PTGS2 and what do prostaglandins do to them?
Joints/soft tissue - pain/inflammation;
Colon cancer - cytoprotecton and anit-apoptotic;
Uterus - luteolysis; endothelium - vasodilation and platelet resting
What are the two targeted tissues of PTGS1 and what do prostaglandins do to them?
Gastric mucosa - cytoprotection and anti-apoptotic
Platelets - aggregation and vasoconstriction
What is the targeted tissue of 5-LOX and what does it do to them?
airways - bronchoconstriction and mucus secretion.
Explain the PGE2 pathway; which G proteins are involved and what occurs?
PGE2 binds to the E2 receptor which recruits and activates G proteins which can either activate adenyl cyclase to produce camp or inhibits adenylate cyclase . Adenylate cyclase will produce CAMP which can activate various pathways.
Explain the TXA2 receptor pathway, what G proteins are involved, what do these G proteins activate?
TXA2 binds to TPb which recruit and activate Gq proteins which activate phospholipase C to produce DAG and IP3 which activate various pathways.
What all can Eicosanoids cause? 8 things
Neutrophil and Eosinophil recruitment and activation mast cell maturation Vasodilation and leakage SM contraction Platelet aggregation Enhanced epithelial barrier function Hyperalgesia
What are the four cardinal signs of inflammation and what are they mediated by?
Rubor - redness due to vasodilation
Tumor - swelling due to vascular permeability
Calor - fever due to activation of leukocytes
Dolor - pain due to increase nocipetion
Mediated by Eicosanoids
What can glucocortecoids do to Eicosanoids and how?
inhibit them via Annexin A1 which inhibits phsopholipase A2
What are the effects of Glucocorticoids?
Suppression of inflammation and immune response, catabolic -release AA; and liver gluconeogenesis
What do glucocorticoids promote?
glucose concentration to the brain at the expense of tissues and immune response (because they both have lots of energy)
What happens if we block PTGS1 and 2?
We blockPGH2 and Prostaglandins, prostacyclins, thromboxanes
Explain what happens during cyto-protection and inflammation
Mild irritant in stomach > activate inflammatory pathways> arachondic acid released > in mucosa, PTGS1 > PGH2 > PGE2 activates phospholipase C > activate G1 pathway > PLC > anti-apoptotic increase mucus
Mild irritant has a 5-LOX enzyme > creates leukotriene B4
What can inhibitors of PTGS1/2 do?
inhibitors reduce inflammation and relieve pain but may cause ulcers
