1. Metabolism of dietary lipids Biochemistry Department

3. © I L O Intended Learning Outcomes By the end of this lecture, the student should be capable of: 1.Recognizing the different types of complex lipids. 2.Finding the role of different complex lipids. 3.Identifying the structure of complex lipids. 4.summarizing the synthesis and degradation of complex lipids. 5.explaining the biosynthesis and function of some important eicosanoides. 6.Describing some abnormalities in complex lipid metabolism

4. Prostaglandins and related compounds A large family of bioactive lipids. Act as paracrine/autocrine hormones with very short half lives Prostaglandins,Thromboxanes &leukotrienes are designated by PG, TX & LT.

6. Categorization of Prostaglandins

7. The subscript number indicates the number of double bonds in the molecule.

8. Eicosanoides: In general:They regulate local inflammation but each molecule has specific effects: Prostaglandin E 2 Vasodilator (VD) Prostaglandin F 2 Vasoconstriction (VC) Prostacyclin (PGI 2 ) (VD)+inhibits plat.agg. Thromboxane A 2 (VC) +stimulates plat.agg. Leukotrienes: = allergic mediators Different PGs are made by different cell types. eg. Thromboxane A 2 made by platelets Prostacyclin made by vascular endothelium

10. -1 st step is Oxidative cyclization of arachidonic acid to yield PGH2 by PG-Synthase= (prostaglandin endoperoxide synthase. -PGH2 is converted to a variety of prostaglandins and thromboxanes, by cell-specific synthases.

11. Oxidative cyclization (prostaglandin endoperoxide synthase) =COX+Peroxidase (20:4  5,  8,  11,  14) Linoleic Acid(Diet)

12. PG- endoperoxide synthase (PGH synthase) PG-synthase is an endoplasmic reticulum membrane-bound enzyme with two catalytic activities: fatty acid cyclooxygenase (COX), requiring 2O 2, and peroxidase, depending on reduced glutathione.

13. Isozymes of PGH synthase (COX)

15. [Systemic inhibition of COX-1, with subsequent damage to the stomach and the kidneys, and impaired clotting of blood, is the basis of aspirin's toxicity.] Inhibitors specific for COX-2 (for example, celecoxib) were designed to reduce pathologic inflammatory processes while maintaining the physiologic functions of COX-1; however, their use has been associated with increased risk of heart attacks.

16. PGH2 Summary of synthesis and inhibition of PG

19. C. Role of prostaglandins in platelet homeostasis

21. Summary of functions of LTs, PGs & TXs LTA4 (LeukotrieneA4) Produced in leukocytes, platelets, mast cells and heart and lung vascular tissues.