1. Introduction to Lipids Structure & Functions

2. Objectives Functions of lipid compounds Clinical problems Lipid compounds of physiological importance Complex lipids: Phospholipids, lipoproteins and glycolipids

3. heterogeneous groupwater- insoluble molecules related to fatty acids. Lipids are heterogeneous group of water- insoluble molecules related to fatty acids. soluble in non-polar They are soluble in non-polar (organic solvents (benzene, ether, chloroform & acetone). B/c they are insoluble: 1.Compartmentalized ( membrane- associated lipids or as TAG in adipocytes. 2.Associated with proteins lipoproteins

4. Lipids’ve many many functions Lipids’ve many many functions : Major source of energy (1g=9kcal) Hydrophobic barrier Fat soluble vitamins ( coenzymes, regulation PGs& steroid hrs play a major regulatory roles in body’s homeostasis

5. Lipids and Related Clinical Problems Obesity Atherosclerosis and hypertension Coronary heart diseases

6. A. Simple Lipids: B. Complex Lipids:

7. Ionized at pH=7, (pK=4.8) Long-chain FA the hydrophobicity predominates Fatty Acids FA has amphipathic nature. CH 3 (CH 2 ) n COOH HydrophobicHydrophilic  >90% of FA in plasma in the form of esters contained in lipoproteins. fasting & starvation  Low levels of free fatty acids are in tissues, but imp. amn. maybe found during fasting & starvation  Free FA’re transported by serum albumin = hydrocarbon chain (alkyl chain )

8. Free Fatty Acids (FFA) 1. Chain length: Short-chain and Medium-Chain Long-Chain e.g., Palmitic acid 16:0 Very long-chain e.g., Nervonic acid 24:1 2. Degree of saturation: Saturated: No double bonds Unsaturated: Mono- or poly-unsaturated Cis- or trans-form 3. Branched Vs straight-chain 4. Essential fatty acids

9. Arachidonic ac. is an essential if linoleic acid is missing.

10. Unsaturated FA: monounsat.( one =)e.g, nervonic ac polyunsat. (two=)e.g., linoleic ac.,(three=) eg α - linolenic ac., Addition of double bonds: Tm ↓↓ Tm Increase chain length: ↑↑ Tm ↑↑ Tm Tm =melting temp/

11. Trans F.A. Are chemically classified as unsaturated f.a., but behave more like saturated f.a. They elevate serum LDL & increase the risk of CVS They don’t occur naturally in plants & occur in small amounts in animals Trans f.a. are formed during hydrogenation of liquid vegetable oils (margarine)

12. fluid nature of those lipids The presence of bouble bonds in some of LCFA of membrane FA maintain the fluid nature of those lipids

13. Free fatty acids cannot be used as a fuel for RBCS & Brain

14. Saturated Fat high levels of total plasma cholesterol & LDL-cholesterol Consumption of saturated fats is strongly associated with high levels of total plasma cholesterol & LDL-cholesterol Thus there is ↑ risk of CVS Main sources: dairy & meat products, vegetable oils as coconut & palm oils

15. *Phytanic acid’s (3,7,11,15 tetramethyl palmitic ac.) present in ↑↑ in dairy products. Branched F.A.

16. Triacylglycerols Storage form in adipose tissue ~ 90% of dietary lipids Glycerol plus 3 fatty acids Blood transport: Chylomicrons and VLDL

17. Acetone Acetoacetate 3-hydroxybutyrate 1. Water-soluble 2. Diabetic Ketoacidosis Ketone Bodies Ketone Bodies:

19. Phospholipids & Glycolipids

20. Phospholipids PL are ionic polar structure formed of an alcohol that is attached by bridge to a back bone either diacylglycerol or sphinogosine A hydrophilic head Long hydrophobic Tail

21. A. Glycerophospholipids Glycerol-containing phospholipids 1. Phosphatidylcholine (Lecithin) e.g., Surfactant (Dipalmitoylecithin) 2. Cardiolipin (antigenic) 3. Phosphatidyl inositol (signaling molecule) B. Sphingo-phospholipids: Sphingosine-containing phospholipids: e.g., sphingomyelin (Myelin sheath) Phospholipids

22. Sphingolipids The sphingolipids include:  sphingomyelins  glycosphingolipids They are essential components of cell membrane ( greatest in nerve tissue).

23. Sphingolipids Sphingosine Ceramide Precursor of glycolipids Ceramide: Parent Sphingolipid Compound

24. A sphingomyelin Alcohol at C-1 is esterified to Phoshorylcholine Important constituents of myelin in nerve fibers The only significant sphingolipids in humans

25. Clinical Significances of Glycosphingolipids outer leaflet present in the outer leaflet of the plasma membrane. carbohydrate moieties of glycolipids :  antigenic determinants on the surfaces of cells (e.g.,blood group antigens.)  cell surface receptors GM1  sources of various embryonic antigens

26. Cholesterol Structure Sterols: are steroids with 8-10 carbon atoms in the side chain at C-17 & OH at C-3 Cholesterol is the major sterol in animal tissues It is a sterol (with 8 carbons at C17,= bet 5&6)

27. Overview and Functions  Major Sterol of animal tissues  Component of cell membranes  Precursor for: Bile acids & salts Vitamin D Steroid hormones: Mineralocorticoids e.g., Aldosterone Glucocorticoids, e.g., Cortisol Sex hormones, e.g., Testosterone Estrogen & progesterone  Hypercholesterolemia: Atherosclerosis & CAD

28. Cholesterol: Types Free cholesterolEsterified cholesterol OH at C3 Hydrophobic Membranes Plasma Transport Free Less Found Less LDL/HDL Fatty acid More Absent Most HDL/LDL CONT’D

29. Lipoprotein Structure Protein part: Apoproteins or apolipoproteins Abbreviations: Apo-A, B, C Functions: Structural and transport function Enzymatic function Ligands for receptors Lipid part: According to the type of lipoproteins Different lipid components in various combinations

30. Lipoprotein Structure

31. Chylomicrons Very low density Lipoprotein (VLDL) Low density Lipoprotein (LDL) High density Lipoprotein (HDL)

32. Plasma Lipoproteins Triacylglycerol transport: Chylomicrons:TG of dietary origin VLDL: TG of endogenous synthesis Cholesterol transport: LDL: Mainly free cholesterol HDL: Mainly esterified cholesterol

33. Take Home Message  Lipids are heterogeneous group of compounds  Lipids are relatively water-insoluble  Simple lipids: FFA, TG, Ketone bodies, Cholesterol  Complex lipids: e.g., Phospholipids, Lipoproteins  Lipids have important physiological functions  Lipid disorders are the basis for common human diseases, namely obesity and atherosclerosis