metabolism of unsaturated fatty acids & eicosanoids
TRANSCRIPT
![Page 1: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/1.jpg)
Metabolism of Unsaturated FattyAcids & Eicosanoids
![Page 2: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/2.jpg)
Eicosanoids
• Prostaglandins • Thromboxanes • Leukotrienes • Lipoxins
![Page 3: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/3.jpg)
• Prostaglandins– Inflammation– Produce pain– induce sleep – involved in the regulation of blood coagulation– Reproduction
![Page 4: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/4.jpg)
• Leukotrienes – Muscle contractant – Chemotactic properties• Important in allergic reactions and inflammation
![Page 5: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/5.jpg)
• Essential fatty acids– Linoleic and α-linolenic acids– arachidonic acid can be formed from linoleic acid
• Double bonds can not be introduced beyond the Δ9 position
![Page 6: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/6.jpg)
Structure of some unsaturated fatty acids
![Page 7: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/7.jpg)
• Monounsaturated fatty Acids are synthesized by Δ9 desaturase system
• SYNTHESIS OF POLYUNSATURATED FATTY ACIDS– DESATURASE– ELONGASE
• The desaturation and chain elongation system is greatly diminished in the starving state
![Page 8: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/8.jpg)
![Page 9: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/9.jpg)
![Page 10: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/10.jpg)
• Essential fatty acids– often in the 2 position of phospholipids– structural integrity of the mitochondrial
membrane
![Page 11: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/11.jpg)
Conversion of linoleate to arachidonate
![Page 12: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/12.jpg)
• In essential fatty acid deficiency– Nonessential polyenoic acids of the ω9 family
replace the essential fatty acids in phospholipids• The triene:tetraene ratio in plasma lipids • Trans Fatty Acids Are Implicated in Various
Disorders– Trans fatty acids compete with essential fatty acids– they are structurally similar to saturated fatty acids
• promotion of hypercholesterolemia and atherosclerosis
![Page 13: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/13.jpg)
EICOSANOIDS
• FORMED FROM C20 POLYUNSATURATED FATTY ACIDS • act as local hormones
– Functioning through G-protein-linked receptors
• C20 eicosanoic acids derived from– Essential fatty acids– Directly from dietary arachidonate and eicosapentaenoate
• by the – Cyclooxygenase pathway
• PROSTANOID SYNTHESIS
– Lipoxygenase pathway
![Page 14: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/14.jpg)
EICOSANOIDS
• Each cell type produces only one type of prostanoid
![Page 15: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/15.jpg)
![Page 16: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/16.jpg)
![Page 17: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/17.jpg)
Essential Fatty Acids
• Physiologic Effects– Prostaglandin Synthesis – Membrane formation
![Page 18: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/18.jpg)
Conversion of arachidonic acid to prostaglandins and thromboxanes of series 2.
![Page 19: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/19.jpg)
LEUKOTRIENES & LIPOXINS
• By LIPOXYGENASE PATHWAY• The leukotrienes– a family of conjugated trienes • from eicosanoic acids
– Leukocytes, mastocytoma cells, platelets, and macrophages
• Lipoxins– a family of conjugated tetraenes • arising in leukocytes
![Page 20: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/20.jpg)
Conversion of arachidonic acid to leukotrienes and lipoxins of series 4.
![Page 21: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/21.jpg)
CLINICAL ASPECTS
• Essential Fatty Acid Deficiency – Symptoms • Skin Lesions & Impairment of Lipid Transport
• Abnormal Metabolism of Essential Fatty Acids– Cystic fibrosis – Cirrhosis and alcoholism– Zellweger’s syndrome
![Page 22: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/22.jpg)
• Thromboxanes– Vasoconstriction
• Contraction of smooth muscle
– Platelet aggregation
• Prostacyclins (PGI2)– Inhibitors of platelet aggregation
• Prostaglandins– increase cAMP in platelets, thyroid, corpus luteum,fetal
bone, adenohypophysis, and lung– Reduce cAMP in renal tubule cells and adipose tissue
![Page 23: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/23.jpg)
Leukotrienes & Lipoxins
• Potent regulators of many disease processes– Slow-reacting substance of anaphylaxis (SRS-A)• Mixture of leukotrienes C4, D4, and E4
– Constrictor of the bronchial airway musculature – together with leukotriene B4 also cause vascular permeability
» Attraction and activation of leukocytes
• Leukotrienes are vasoactive • Lipoxins – Vasoactive and immunoregulatory function
![Page 24: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/24.jpg)
• Higher animals have Δ4, Δ5, Δ6, and Δ9 desaturases but cannot insert new double bonds beyond the 9 position of fatty acids. Thus, the essential fatty acids linoleic (ω6) and α-linolenic (ω3) must be obtained from the diet.
![Page 25: Metabolism of Unsaturated Fatty Acids & Eicosanoids](https://reader033.vdocuments.site/reader033/viewer/2022061607/56649e2a5503460f94b17638/html5/thumbnails/25.jpg)
Eicosanoids
• Derived from– C20 (eicosanoic) fatty acids• Synthesized from the essential fatty acids
– Comprise– Prostaglandins – Thromboxanes– Leukotrienes– Lipoxins
• Important groups of physiologically and pharmacologically active compounds.