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Prostaglandins.bioch212pptx

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Biochemistry …

Biochemistry
Second Year

Published in: Health & Medicine

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  • 1. DR SHAMIM SHAIKH MOHIUDDIN DEPARTMENT OF BIOCHEMISTRY UNIVERSITY OF DAMMAM 1
  • 2. Outline of this lecture topics……… 1. Overview of prostaglandins (slide no 3) 2. Different Types of Prostaglandins (slide no 4) 3. Biosynthesis of Prostaglandins (slide no 5) 4. Inhibition of Prostaglandins synthesis (slide no 7) 5. Biochemical actions of Prostaglandins (slide no 8) 6. Biomedical application of Prostaglandins (slide no 11) 2
  • 3. -Prostaglandins (PGs) and related compounds ie Prostacyclines (PGI), Thromboxanes ( TXA), Leukotrienes ( LT) and Lipoxins are collectively known as eicosanoids. -Most are produced from arachidonic acid, a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid). -The eicosanoids are considered "local hormones." as…… -They have specific effects on target cells close to their site of formation. -They are rapidly degraded, so they are not transported to distal sites within the body. Overview of prostaglandins 3
  • 4. Outline of different types of Prostaglandins 4
  • 5. Cell Membrane Phospholipids Phospholipase A2 Arachidonic Acid Prostaglandin G2 ( PGG2) Cyclooxygenase 1 & 2 Thromboxane A2Prostacyclin (PGI2) Prostaglandin F2α ( PGF2α) Prostaglandin E2 (PGE2) Prostaglandin H2 ( PGH2) PGI2 synthase reductase TXA2 synthase isomerase peroxidase Biosynthesis of Prostaglandins CORTICOSTEROIDS ASPIRIN INDOMETHACIN IBUPROFEN 5
  • 6. -Arachidonic acid(5,8,11,14 –eocosatetraenoic acid) is the precursor for most of the prostaglandins in human. -It occurs in the endoplasmic reticulum in the following stages…… 1. Phospholipase A2 release arachidonic acid from membrane bound phospholipids. Hormones such as epinephrine or bradykinin stimulates this reaction. 2. Oxidation and cyclization of arachidonic acid to PGG2 by cyclooxygenase 1 & 2 3. PGG2 is then converted to PGH2 by a reduced glutathione dependent peroxidase. 4. PGH2 serve as immediate precursor for synthesis of different types of prostaglandins 6
  • 7. Inhibition of Prostaglandin synthesis Following compounds can inhibits prostaglandin synthesis by following mechanism…… 1.Corticosteroids- Prevent the formation of Arachidonic acid by inhibiting Phospholipase A2 2.Aspirin-Irreversible inhibitor the enzyme Cyclooxygenase 3.Indomethacin- Reversible inhibitor of the enzyme cyclooxygenase 7
  • 8. Biochemical actions of Prostaglandins 1.Regulation of blood pressure PGE2 and PGI2 are vasodilators in vascular bed Increased blood flow and decrease peripheral resistance Lower blood pressure 2. Inflammation PGE1 and PGE2 induce the symptoms of inflammation (redness, swelling etc.) due to vasodialation 3. Reproduction PGE2 and PGF2α causes contraction of uterine smooth muscle in pregnant woman results in leads to 8
  • 9. 4. Pain and fever Pyrogens (fever producing agent) promotes prostaglandin biosynthesis Formation of PGE2 in hypothalamus Fever associated with pain 5. Regulation of gastric secretion -Prostaglandins inhibit gastric secretion -Prostaglandins stimulate pancreatic secretion and increase the motility of intestine diarrhea Leads to causes causes 6. Influence on immune system PGE decreases on immunological functions of B and T lymphocytes 9
  • 10. 7. Effect on respiratory function -PGEs causes bronchial smooth muscle relaxation -PGFs causes bronchial smooth muscle constriction PGE and PGF oppose the actions of each other in the lung 8. Influence on renal function Prostaglandin increases glomerular filtration rate (GFR) Promotes urine output thus thus 9. Effect on platelet aggregation -PGI2 inhibits platelet aggregation -Thromboxane (TXA2) and PGE2 promotes platelet aggregation and blood clotting that might leads to thrombosis 10
  • 11. BIOMEDICAL APPLICATION OF PROSTAGLANDINES 1. Induction of labor at term. Induction of labor is produced by: -infusion of PGF2a (carboprost tromethamine) -PGE2 (dinoprostone) 2.Treatment of peptic ulcer. Misoprostol [Cytotec] -a methylated derivative of PGE1 -is approved for use in patients taking high doses of nonsteroidal antiinflammatory drugs (NSAIDs) to reduce gastric ulceration. 11