Eicosanoids

Structure, functions and metabolism of eicosanoids

1. Eicosanoids Structure, functions and metabolism R. C. Gupta Professor and Head Department of Biochemistry National Institute of Medical Sciences Jaipur, India

2. Hence, they were named prostaglandins They were first found in seminal fluid and were believed to be synthesized only in prostate gland The first eicosanoids to be discovered were prostaglandins

3. They were found to affect reproductive system, cardio-vascular system, central nervous system, gastro-intestinal tract etc Prostaglandins were later found to have wide tissue distribution They were found to produce profound physiological and biochemical effects

4. T hromboxanes were initially discover ed in thrombocytes L eukotrienes were initially discovered in leukocytes Some other cells were later found to synthesize thromboxanes and l eukotrienes

5. Prostanoic acid has a five-carbon ring and two side chains attached to the ring Prostaglandins (PGs) structurally resemble prostanoic acid, a 20-carbon fatty acid Prostaglandins

6. Depending upon the substituents, the prosta-glandins are divided into PGA, PGB etc The number of double bonds varies from 1-3 Each type is sub-divided according to the number of carbon-carbon double bonds in the side chains

7. For example, PGE 1 means that it is a prostaglandin of type E The subscript shows that it has one carbon-carbon double bond The type of PG is shown by a letter and the double bonds by a subscript

8. Prostaglandins of type F are PGF 1 a , PGF 2 a and PGF 3 a The most important prostaglandins are of types E and F Prostaglandins of type E are PGE 1 , PGE 2 and PGE 3

9. Thromboxanes are similar in structure to prostaglandins with the difference that they have a six-membered oxane ring Thromboxanes They are of several types, e.g. TXA 1 , TXA 2 and TXA 3 etc , depending upon the number of double bonds in the side chains

10. Leukotrienes Leukotrienes are 20-carbon polyenoic fatty acids having a number of substituents Depending upon the substituents, they are divided into LTA, LTB, LTC, LTD and LTE

11. The most important leukotrienes are LTC 4 , LTD 4 and LTE 4 Each type is divided into sub-groups depending upon the number of double bonds which vary from 3-5

12. In LTC 4 , glutathione is attached as a substituent to C 6 In LTE 4 , the substituent is cysteine The substituent is cysteinylglycine i n LTD 4

13. Synthesis of eicosanoids

14. By similar reactions, arachidonic acid (20:4;5,8,11,14) can form: Prostaglandins E 2 and F 2 a Thromboxane A 2 Leukotrienes A 4 , B 4 , C 4 , D 4 and E 4

15. By similar reactions , eicosapentaenoic acid ( 20:5;5,8,11,14,17 ) can form: Prostaglandins E 3 and F 3 a Thromboxane A 3 Leukotrienes A 5 , B 5 and C 5

16. Catabolism of eicosanoids

17. Functions of eicosanoids

18. Actions of prostaglandins Continued …

19. Continued …

20. Actions of thromboxanes

21. Actions of leukotrienes

22. Inhibitors of eicosanoid synthesis

23. Thank you