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Leukotrienes and lipoxins
|How do leukotrienes differ from prostaglandins, prostacyclins, and thromboxanes?
|linear eicosanoids, not cyclic
|What is the role of leukotrienes?
|mediate allergy response, immunity, inflammation
|What is the most serious leukotriene that causes a response 10,000 times (5 orders of magnitude) greater than histamine?
|Peptidoleukotrienes are known to be the active component of what mediator of intense, violent, often fatal allergic rxns?
|slow-reacting substances of anaphylayxis (SRS-A)
|What is the common predominant precursor between cyclic eicosanoids and linear eicosanoids?
|The first step of Arachidonic acid metabolism is it's conversion by what to what?
|Lipoxygenases (LO) convert it to 5HPETE: hydroperoxyeicosatetraenoic acids
|What final products do the three types of lipoxygenases create?
|5-LO = leukotrienes, 15-LO = lipoxins, 12-LO = hepoxilin
|AFter conversion to 5-HPETE, what does 5LO create in it's second catalyzation?
|5-HPETE to Leukotriene A4 - the parent leukotriene
|What must also be present to assist 5LO?
|FLAP - 5-lipoxygenase activating protein
|What are the two reactions of 5LO?
|adds Ox to arachidic acid to make 5-HPETE then, acts as endoperoxidas to remove water and create an double attached Oxygen, peroxy? which is Leukotriene, A4
|What special trait does LTB4 exhibit?
|Chemotactic, attracts immune cells to fight infections
|What important antioxidant is needed as a substrate for LTA4 to convert to other actives such as LTC4, LTD4, LTE4
|glutathione via glutathion-S-transferase
|What do LTC4 and LTE4 do?
|peptidoleukotrienes - they are the actual bad ones - SRS-A's of astma and inflamation
|What is important about omega-3 fatty acids in our diet?
|They form eicosapentaenoic acid (EPA) prostaglandins and leukotrienes derived from them are less physiologically active - decreased inflammation etc..
|What are the Series Number associated with prostaglandins and leukotrienes derived from arachadonic acid?
|Prostaglandins = series 2 Leukotrienes = series 4
|What are the Series Number associated with prostaglandins and leukotrienes derived from eicosapentanoic acid (EPA)?
|Prostaglanidin = series 3 Leukotriene = series 5
|What are the Series Number associated with prostaglandins and leukotrienes derived from eicosatrienoic acid (ETA)?
|Prostaglandins = series 1 Leukotrienes= series 3
|PGH2 synthase is a multifunctional enzyme with two active sites. What operates at each?
|One = cyclooxygenase (COX) Two = endoperoxidase
|How are lipoxins different from other eicosanoids?
|The are ANTI-inflammatory agents
|How do we synthesize lipoxins?
|Why do we still think of arachidonic acid in terms of inflammation if it also makes lipoxins?
|Prostaglandin synthesis is greater than lipoxin synthesis.
|How does aspirin over come the prostaglandin/lipoxin imbalance?
|Aspirin is a suicide inhibitor of the PGH2 pathway. It ihibits COX 1 and COX2, but does not inhibit endoperoxidase at the second active site on PGH2-synthase. So 15-HPETE can make 15-epi-LXA4, which is a version of lipoxin.
|What are aspirin-triggered epilipoxins?
|enantiomers of 15S-HPETE formed when aspirin blocks the COX active site, but does not affect the endoperoxidase site on PGH2-synthatse
|The pharmaceutical industry produces an agent that targets receptors How?
|inhibit release of arachidonic acid from phosphatidyl insositol by steriods that block Phospholipase A.
|What drugs target leukotriene action by inhibiting LTC4-receptors?
|Montelukast (singular) Zarfilukast (Accolate)
|What drug inhibits 5-LO?
|What drug inhibits FLAP