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Biochem Block 6

Prostaglandins Block 6

Three related compounds that are considered eicosanoids? prostaglandins, leukotrienes, thromboxanes
Where are eicosaniods (ie. prostaglandins)made? synthesized in all cells
How do eicosanoids act? How long? act locally with very short half-life
What quantity is needed to elicit a reaction? very small concentration for desired effect
What eicosanoid do platelets synthesize? Why? thromboxane; TXA2, promotes platelet aggregation and local vasoconstriction
What eicosanoid do vascular endothelial cells synthesize? Why? prostacylin; PGI2, inhibits platlet aggregation and stimulates vasodilation
What are the two eicosanoids with opposing actions? From what cells? thrombaxane from platelets vs. prostacylin from vascular endothelial cells
Thromboxane causes what reactions? platelet aggregation vasoconstriction
Prostacylin causes what reactions? platelet dispersion vasodilation
Which type eicosanoid does aspirin affect? suicide inhibitor for thromboxane - with no nucleus the platelets cannot make more of it.
What is the most common precursor of prostaglandins? arachidonic acid
What is the dietary precursor of a prostaglandin? linoleic acid
Where does arachidonic acid come from? released from membrane-bound phospholipids by phospholipase A2
The important enzyme for leukotriene creation lipoxygenase
the important enzyme for prostacylin and thromboxanes? cyclo-oxygenase
The two enzymes Luchia want you to know regarding prostaglandin production phospholipase A2 cyclo-oxygenase
The two important anti-inflammatory drugs that inhibit prostagladins? steriodal drugs (glucocorticoids) & NSID
What do glucocorticoids inhibit? phospholipase A2, thus prevent production of arachidonic acid
What do Aspirin and other non-steroidal anti-inflammatory drugs inhibit? cyclooxygenase, thus preventing PGH2
What is PGH2? What is the 2? Prostaglandin endoperoxide - the two indicates where the double bond is located
Where does glucocorticoid regulation of inflammation reactions (such as asthma attack) occur? It is steriod - so in nucleus!!! down regulates expression of phospholipase A2 gene
What is the difference between COX1 and COX2 isozymes? COX 1 is made constantly in most tissue COX 2 is inducible in a limited tissues
What is the role of COX1? maintenance of healthy gastric tissue, renal homeostasis, platelet aggregation
What is role of COX2? activated in immune response and inflammation; causes the pain, heat, redness, swelling, and fever. My COX does 2
How does aspirin work against COX1 & COX2? Non Competitive and Non-selective acetylation: irreverisibly inactivates it
Why does low dose aspirin therapy work? platelets have life span of 7-10 days, when taken daily aspirin affects them as they are made.
What effect does aspirin have on vascular endothelial cells? It mildly minimizes prostacyclin, but the nucleated cells can make more!
What effect is created by low dose aspirin therapy? mild defect in hemostasis, or blood clotting. Prevents the thrombus formation in area of atherosclerotic plaque
Specific area low dose aspirin helps in the vascular tree coronary arteries
What is the basis of aspirins and other NSID's toxicity? systemic inhibition of COX-1 with damage to stomach, kidneys and impaired clotting
What is the problem with the COX-2 inhibitors linked to increase in heart attacks
What does COX-2 do in the body when over produced, such as chronic insult up-regulates cytokines, endotoxin, growth factors and tumor promotors.
In healthy endothelium, prostacylin is released into the blood. What effect does this have plasma prostacyclin binds to receptors activating cAMP. cAMP inhibits release of granules with platlet aggregating agents
What are platelet aggregating agents ADP + Serotonin
TXA2 promotes what 4 things 1. vasoconstriction 2. platelet aggregation 3. mobilizes intracellular calcium 4. contraction of smooth muscle
PGI2 promotes what 2 things 1. vasodilation 2. inhibits platelet aggregation
Bonus question: PGF2(alpha) does what smooth muscle contraction stimulate uterine contraction
Bonus question:PGE2 does what vasodilation relaxes smooth muscle used to induce labor
Why would the body secrete TXA2 and PGI2 at the same time? limits the formation of thrombi to the sight of injury
If you have asthma what eicosanoids are causing you trouble? Leukotrienes
What forms leukotrienes from arachinic acid? arachidonic acid catalyzed by 5-lipoxygenase to 5-HPETE. This forms different leukotrienes depending on the tissue
How does aspirin therapy help asthmatics? It does not help. Must use steriods
Created by: El Diablo on 2010-02-11

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