Fatty Acid Metabolism

1. Fatty Acid Metabolism Wolfgang Bayer, Ph.D. AK World Congress, May 2006,Vienna

2. Fat – what is it? H2-C-OOC-(CH2)14-CH3 H-C-OOC-(CH2)14-CH3 H2-C-OOC-(CH2)14-CH3 triglycerid H2-C-OH + HOOC-(CH2)14-CH3 H-C-OH + HOOC-(CH2)14-CH3 H2-C-OH + HOOC-(CH2)14-CH3 glycerol palmitic acid - 3 H2O Natural fats and oils are comprised of glycerol esters of the higher even-numbered fatty acids = triglycerides

3. fatty acid 1 fatty acid 1 glycerol glycerol fatty acid 2 fatty acid 2 fatty acid 3 =phosphate choline P P triglycerid phospholipid (phosphatidylcholin) fatty acid fatty acid sphingosine sphingosine sugar choline P sphingolipid (sphingomyelin) glycolipid (cerebrosid)

4. fatty acids saturated fatty acids unsaturated fatty acids monounsaturated fatty acids polyunsaturated fatty acids ω-3 fatty acids ω-6 fatty acids

5. Fatty acids - nomenclature What is the designation for this fatty acid? ω-end δ-end 18 15 12 9 1 cis-9,12,15-octadecatrienoic acid 18:3, ω-3 α-linolenic acid

6. stearic acid, 18:0 saturated mono- unsaturated poly- unsaturated oleic acid linoleic acid, α- α-linolenic acid, docosahexaenoic acid,

7. Cis and trans fatty acids trans cis H3C CH3 H3C H C C C C H H H CH3 Cis fatty acids are the naturally occurring forms of fatty acids. Trans fatty acids are produced when fats are hydrogenated (margarine). They have rigid structures and are described as having atherogenic properties.

8. Uptake and synthesis of fatty acids (1) In the duodenum, nutritional fats (triglycerides) are split by lipases into monoglycerides and free fatty acids. Following absorption, triglycerides are resynthesized, then transported to tissues, or stored in fatty tissues, by means of chylomicrons. Fatty acids can be synthesized endogenously from glucose by means of the enzyme fatty acid synthase (FAS). This process results in saturated fatty acids with up to 16 C atoms – palmitic acid (C 16:0).

9. Uptake and synthesis of fatty acids (2) Following reactions result in extended saturated and monounsaturated fatty acids, but not in the poly-unsaturated C 18 fatty acids (ω-3 and ω-6). Triglycerides can be synthesized from the fatty acids produced in the liver. They enter the bloodstream bound to VLDLs. Fats are stored in fat cells (adipocytes), where they are continuously built up and broken down. The amount of body fat is approx. 8-15 kg in men and 10-20 kg in women.

10. Fatty acid breakdown by ß-oxidation The fatty acid is short-ened by 2 C atoms in each reaction cycle. Acetyl-CoA is prod-uced, which can then be metabolized to CO2 and ATP in the citrate cycle. 1 mol of palmitic acid produces 106 mols of ATP, equiv-alent to 3,300 kJ/mol. = coenzyme A

11. Fatty acid breakdown and energy production fatty tissue fat lipolysis fatty acids bowels triglycerides split fatty acids plasma fatty acids muscle ketones acetyl-CoA ox.phos. ATP liver fatty acids ß-oxidation acetyl-CoA ketogenesis ketones ATP

12. Physiological functions of fatty acids Energy pro-duction in the mitochondria Building blocks of cell membranes Eicosanoid synthesis: immunoregulation, regulation of Insulation: mechanical, electrical vasotonus and brochotonus • Influence lipid metabolism, lower triglyceride levels • Regulate central nervous and sensory functions • Important during pregnancy: development of foetal nervous system and brain

13. Omega-3 and omega-6 fatty acids • α-linolenic and linoleic acid, the basic components of the ω-3 and ω-6 fatty acids, cannot be synthe-sized by the human organism. • These are essential fatty acids that must be included regulary, in balanced amounts, in the diet. D.A.CH. recommended ratio ω-6/ω-3: 5/1. Ratio of ω-6 to ω-3 fatty acids For further information: www.labor-bayer.de

14. Omega-3 and omega-6 fatty acids • Omega-3 and omega-6 fatty acids cannot be transformed into one another. • Other longer-chained fatty acids can be made from α-linolenic acid and linoleic acid by means of desaturation and elongation steps. (One reads this frequently in the literature – but is it really true?) For further information: www.labor-bayer.de

15. omega-9-series omega-6-series omega-3-series oleic acid 18:1, ω-9 linoleic acid 18:2, ω-6 α-linolenic acid 18:3, ω-3 δ-6-desaturase 18:2, ω-9 γ-linolenic acid 18:3, ω-6 18:4, ω-3 elongation 20:2, ω-9 dihomo-γ-linolenic acid 20:3, ω-6 20:4, ω-3 δ-5-desaturase eicosatrienoic acid 20:3, ω-9 arachidonic acid 20:4, ω-6 eicosapentaenoic acid 20:5, ω-3 elongation eicosanoides eicosanoides eicosanoides series 1 series 2 series 3 PGE1,PGI1,TXA1 PGE2,PGI2,TXA2 PGE3,PGI3,TXA3 LTB4, LTC4 LTB5, LTC5 22:5, ω-3 δ-4-desaturase pro- inflammatory anti- inflammatory docosahexaenoic acid 22:6, ω-3

16. The eicosanoids 1.Prostaglandins can be produced in numerous tissues and posses tissue-specific effects, e.g. in enzymatic systems. 2.Prostacyclins are produced in endothelial cells of the blood vessels. They inhibit thrombocyte aggregation and dilate blood vessels. 3. Thromboxanes, the antagonists of the prostacyclins, are produced in thrombocytes. They lead to thrombocyte aggregation and stenosis of blood vessels. 4. Leukotrienes are produced in leucocytes and other cells and contribute to allergic and inflammatory reactions.

17. ω-6 ω-3 anti-inflammatory pro-inflammatory

18. Omega-3 fatty acids and markers of inflammation ,ω-6 ,ω-3 James, M.J. et al.: Am. J. Clin. Nutr. 71, 343S-348S, 2000 + 9 g fish oil + 9 g fish oil

19. Fatty acid status 41 years old female patient, intake of 3 table-spoons flaxseed oil 5 times a week for months

20. Danke!