this is the brief introductory prsentation about lipids and its physiological significance.

1. LIPIDS OF PHYSIOLOGICAL SIGNIFICANCE & ITS ROLE IN HEALTH AND DISEASES Presented by, Shruti Sharma (D.Phil Scholar)

4. Classification of fatty acids;- Fatty acids Saturated FA Unsaturated FA

6. Unsaturated fatty acids;- Unsaturated fatty acid: a fatty acid with one or more points of unsaturation. Unsaturated fats are found in foods from both plant and animal sources. Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids.

7. Divisions of unsaturated fatty acids;- Unsaturated Fatty acids MUFA PUFA Eicosanoids

11. SERUM LIPIDS— >raises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol >increases the ratio of total cholesterol to HDL cholesterol, a powerful predictor of the risk of CHD >increase the blood levels of triglycerides , of Lp(a) lipoprotein, and reduce the particle size of LDL cholesterol: further raise the risk of CHD. >trans fatty acids have markedly adverse effects on serum lipids Physiological effects of trans fatty acids continued…

12. Systemic inflammation— inflammation: an independent risk factor for atherosclerosis, sudden death from cardiac causes, diabetes, and heart failure the inflammatory effects of trans fats may account in part for their effects on cardiovascular health For example, the difference in C-reactive protein levels ; 2.1 percent vs 0.9 percent intake: an increase in cardiovascular risk of approximately 30 percent. Physiological effects of trans fatty acids continued…

13. ENDOTHELIAL-CELL FUNCTION-- increased levels of several markers of endothelial dysfunction: for eg;- soluble intercellular adhesion molecule, soluble vascular-cell adhesion molecule, and E-selectin Physiological effects of trans fatty acids continued…

14. Polyunsaturated fatty acids;- Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points, found in nuts and vegetable oils such as safflower, sunflower, and soybean, and in fatty fish. They possess protective role on human health.considered as beneficial for consumpmtion.

16. Omega-3-fatty acids- Benefits- >Lower PGE2s level >Anti-inflammatory >Lower triglyceride and cholesterol levels >Benefits vision and >brain function >Decrease Skin >inflammation >Inhibit platelet adhesion >Increase insulin sensitivity

17. Omega-6 fatty acids- Linoleic fatty acid Arachidonic acid Benefits- Platelet aggregation, cardiovascular diseases, and inflammation. Reduce the symptoms of eczema and psoriasis. Clear up different types of acne.

21. Sterols ;- Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring. Cholesterol- best known steroid because of its association with atherosclerosis and heart diseases. Contains same steroid nucleus. Exclusively present in animals . Functions;- --Bile acids – Sex hormones – Adrenal hormones – Vitamin D --Cardiac glycosides

23. Lipoproteins;- Lipoproteins are th macromolecular complex of lipids and proteins. Transportation of lipids in the blood. Structure of lipoproteins ;- Hydrophobic lipids (TG, CE) in core; Hydrophilic lipids (UC, PL) on surface

24. Classes of lipoproteins ;- Chylomicrons, VLDL, LDL HDL > 30 nm 9–15 nm 20–22 nm D<1.006 g/ml D=1.019-1.063g/ml D=1.063-1.21 g/ml Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000; 149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994

28. Chylomicrons ;- TG rich . Synthesized in intestine. Transports endogenous TGs. Hydrophobic Core Triglyceride (93%) Cholesteryl Esters (1%)

29. VLDL;- rich in CE and TGs- Surface Monolayer Phospholipids (12%) Free Cholesterol (14%) Protein (4%) Hydrophobic Core Triglyceride (65%) Cholesteryl Esters (8%)

30. LDL;- cholesterol rich. Surface Monolayer Phospholipids (25%) Free Cholesterol (15%) Protein (22%) Synthesized from VLDL in blood circulation. Transports cholesterol from liver and delivers to other tissues.

31. High density lipoprotein- Surface Monolayer Phospholipids (25%) Free Cholesterol (7%) Protein (45%) Promotes re-esterification process of cholesterol.

32. HDL Subpopulations Rye et al. Atherosclerosis 1999;145:227-238. Apolipoprotein Composition A-I HDL A-I/A-II HDL A-II HDL Particle Shape Discoidal Spherical Lipid Composition TG, CE, and PL Particle Size HDL 2b HDL 2a HDL 3a HDL 3b HDL 3c

36. Arachidonic acid and the brain-- One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function. The level of AA in the brain is comparable to that of DHA. At 8–11% of the fatty acid phospholipids, it is severalfold higher than any other (n-6) PUFA (by comparison, linoleic acid content is ;1%). Connell et al,(2007 ) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivated receptor-g (17). Furthermore, it has been shown that AA, as well as DHA, activates syntaxin-3, a critical factor in the growth and regeneration of neurons.

37. Prevention of cancer;- Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast, prostate, and colon cancer cell lines cultured outside the body Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary, prostate, and intestinal tumors

40. Diagrammatic representation of the disease (atherosclerosis)-

41. Metabolic disorders of cerebrosides Dermatitis,skeletal deformation,hoarseness. ceramide ceramidase Ref- Harper’s biochemistry Farber’s disease Enlarged liver and spleen sphingomyelin sphingomyelinase Niemann-pick disease Enlarged liver and spleen, eroison of long bones ,mental retardation glucosylceramide B-glucosidase Gaucher’s disease Mental retardation,complete loss of myelin sheath. galactosylceramide B-galactosidase Krabbe’s disease Skin rashes,kidney failure galactosylceramide A-galactosidase. Fabry;’s disease Mentalretardation,blindness,muscular weakness. symptoms gangliosides Lipid accumulating hexosaminidase Enzyme deficiency Tay –sachs disease diseases

42. Lipoprotein disorders ;- Hyperlipoproteinemias- --do-- Chylomicron and VLDL Ref- Harper’s biochemistry --do-- v May/may not increase TGs Overproduction of TGs lv high TGs and cholesterol Abnormality in apo -e lll high TGs and cholesterol Overproduction of apo-b llb Very high cholesterol Deficiency of LDLreceptors lla increase Risk of athersclerosis chylomicrons Increased plasma lipid most Deficiency of lipoproteinlipase Metabolic defect l Hy. Lipo.types

43. Infant repiratory distress syndrome- Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin . It prevents collapsing of the alveoli and also decreases the surface tension . Deficiency is common in young infants. Xanthomatosis;- Deposition of yellow-orange colours lipids occurs in the liver ,spleen and flat bones. Usually related with severe hypercholesterolemia and hyperlipidemia. Phrynoderma or Toad skin ;- Caused due to the deficiency of essential fatty acids. Horny eruptions occurs on posterior and lateral limbs.poor wound healing. Multiple sclerosis;- It is a demyelinating condition. loss of both phospholipids and sphingolipids occurs from white matter. Neurodegeneration is common.

44. Defects in the metabolism of essential fatty acids - Cystic fibrosis,Acrodermatitis enterohepatica,Hepato renal syndrome, Crohn’s disease,Cirrhosis, Alcoholism, Reye's syndrome etc. Zwellweger’s disease;- Rare disorder. occurs due to the accumulation of long chain polyenoic fatty acids in the brain. Causes loss of functions and neural degeneration . Dicarboxylic aciduria- It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme.

45. Common Atherogenic dyslipidemias ) 􀂃 polygenic inheritance – dietary component – secondarily enhanced by insulin resistance (see further why) 􀂃 prognosis of combined hyperlipidemia is worse than that of hypercholesterolemia 􀂃 main features – impaired clearance of TAG by LPL (􀀪 insulin) from chylomicrons -> increased TAG and increased delivery of TAG for liver – increased production of VLDL by liver (􀀪 insulin) from TAG, FFA from adipose tissue (􀀪 insulin) and glucose (􀀪 insulin) – therefore increased conversion of VLDL to LDL – low HDL

48. References-- 1) Connell E, Darios F, Broersen K, Gatsby N, Peak-Chew SY, Rickman C, Davletov B. Mechanism of arachidonic acid action on syntaxin- Munc18. EMBO Rep. 2007;8:414–9 2) Granner,K. and Robert,K.(2006). Harper’s illustrated biochemistry .27 th edition.Tata McGraw Hills publication. 3)Satyanarayan,U. (2006). Biochemistry .3 rd edition. Books and Allied (P)Ltd. 4) Whelan ,J.(2008 ).(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain: Food for Thought. Abstract J. Nutr. 138: 2521–2522.

49. Thank you.