Lipids

1. Lipids

2. What are Lipids? • Lipids are non-polar (hydrophobic) organic compounds, insoluble in water, soluble in organic solvents (ether, acetone, carbontetrachloride). • They contain carbon, hydrogen, and oxygen; sometimes nitrogen and phosphorus. • In most cases they yield fatty acids on hydrolysis. • They take place in lipid and plant metabolism.

3. Fatty acids • Fatty acids (FAs) consist of hydrocarbon chain with a carboxylic acid at one end  straight-chain organic acids • Most naturally occurring fatty acids have an even number of carbon atoms • They can be saturated and unsaturated. • Unsaturated fatty acids have lower melting points than saturated fatty acid.

4. Fatty acids • Monounsaturated FAs  one double bond • Polyunsaturated FAs many double bonds • Eicosanoids (include prostaglandins, leukotriens, prostacyclins, thromboxanes) • Double bonds in fatty acids are usually in the cisconfiguration.

6. Linoleic acid • Linoleic acid is a nutritionally essential fatty acid. that must be ingestedby humans and other animals because the body requires itbut cannot synthesize it. • It is found in large conc. in corn, peanut, soyabean oils but not in olive oil. • Absence of linoleic acid by infants  weight loss and ezema.

7. Classification of lipids according to their structures

8. Classification of lipids according to their structures • Simple lipids  esters of FAs (FAT, OIL, WAX) [One or two chemical identities) • Hydrolysis of a simple lipid  Simple lipid + H2Ofatty acid + alcohol • If the alcohol is glycerol (FAT or OIL) • If the alcohol is a monohydric alcohol WAX • Hydrolysis of complex lipids more fatty acids + alcohol +other compound • Phospholipid + H2O (hydrolysis) FA + alcohol + phosphorus + nitrogen compound. • Phospholipids phosphoglyceride or phosphosphingoside • Glycolipid + H2O (hydrolysis)  FA +a carbohydrate + sphingosine

9. Classification of lipids according to their structures • Precursor lipids compounds resulting from hydrolysis of simple or complex lipids (FA, sphingosine) • Derived lipids lipids which are formed due to the transformation of fatty acids (Prostaglandins, Fat-soluble vitamins)

10. Fats and oils • Fats with a melting point below room temperature are called oils.

11. Iodine number • The iodine number of a fat or an oil is the umber of grams of iodine that will react with the double bond present in 100 g of fat or oil • Higher iodine number higher degree of unsaturation • Generally iodine number of animal fats < iodine number of vegetable oils • Iodine number of fats <70 • Iodine number of oils > 70

12. Some uses of lipids in the body • Fats serve as fuel. • Fats serve as reserve supply of food and energy. • Fats are stored in special adipose tissues and serve as a protector for vital organs. • Fats act as heat insulators. • Some lipids allow rapid propagation of electrical signals.

13. Physical properties • White or yellowish solid or liquids • Pure fats and oils are odorless and tasteless. Over a period of time they become rancid and develop an unpleasant odor and tatse. • Lighter than water. • When shaken with water  temporarily emulsion. • Emulsion can made permanent by addition of emulsifying agent such soap. • Fats and oils must be emulsified before they can be digested.

14. Chemical reactions • Hydrolysis 3. Enzyme

15. Saponification

16. Hydrogenation • In Practice not all double bonds are hydrogenated. • Hydrogenation lowers the iodine number.

17. Acrolein test: Test for fats or oils which contain glycerol • Glycerol (KHSO4) (heat)Acrolein (strong odor) • Rancidity: unpleasant odor or taste developed when fats stand at room temperature for a short period of time. • Rancidity is due to hydrolysis and oxidation reactions. • Oxidation of double bonds  short chain aldehydes and acids bad odor and taste (Antioxidant Vit. E and C.) • Fats + Water in butter (in presence of microorganisms)hydrolysis of fats Butyric acid disagreeable odor. • Fats and foods containing fats have to be covered and stored in the refrigerator

18. Cleansing action of soaps • CH3-(CH2)16-COONa (Sodium stearate) • Non-Polar Polar • Hydrophopic Hydrophilic Micelle • Mechanical Washing causes the oil to break down into small drops • Soap emulsifies then the oil and prevents it from coalescing. • Soap acts also as surfactant  lowers surface tension

19. Detergents • Synthetic compounds used as cleansing agents. • Soaps do not work in hard water  insoluble Ca and Mg salts • Detergents work also in hard water • Soaps (alkaline); Detergents (neutral)  Detergents can be used on silks and wool; Sops not. • Detergents: Sodium salts if long chain alcohol sulfates • Example: Sodium laurylsulfate • C12H23OH + H2SO4 C11H23CH2OSO3H + H2O • C11H23CH2OSO3H + NaOH  C11H23CH2OSO3Na + H2O

20. Complex lipids and cell Membranes: an overview Some functions of membranes (40-50% lipids; 50-60% Proteins) Mechanical support. Seperate contents of the cells from the environment Structural support for proteins (pumps; receptors)

21. Introduction to lipids Biochemistry II Self aggregation of lipids non-polar end hydrophobic end) Polar end (hydrophilic end)

22. Glycerophospholipids(phosphoglycerides), are common constituents of cellular membranes. They have a glycerol backbone. Hydroxyls at C1 & C2 are esterified to fatty acids. Glycerophospholipids An ester forms when a hydroxyl reacts with a carboxylic acid, with loss of H2O.

23. Phosphatidate In phosphatidate: • fatty acids are esterified to hydroxyls on C1 & C2 • the C3 hydroxyl is esterified to Pi.

24. In most glycerophospholipids (phosphoglycerides), Pi is in turn esterified to OH of a polarhead group (X): e.g., serine, choline, ethanolamine, glycerol, or inositol. The 2 fatty acids tend to be non-identical. They may differ in length and/or the presence/absence of double bonds.

25. Phosphatidylinositol, with inositol as polar head group, is one glycerophospholipid. In addition to being a membrane lipid, phosphatidylinositol has roles in cell signaling.

26. Phosphatidylcholine, with choline as polar head group, is another glycerophospholipid. It is a common membrane lipid.

27. Each glycerophospholipid includes • a polar region: glycerol, carbonylO of fatty acids, Pi, & the polar head group (X) • non-polar hydrocarbon tails of fatty acids (R1, R2).

28. Structure of phospholipids

29. Sphingolipidsare derivatives of the lipid sphingosine, which has a long hydrocarbon tail, and a polar domain that includes an amino group. Sphingosine may be reversibly phosphorylated to produce the signal molecule sphingosine-1-phosphate. Other derivatives of sphingosine are commonly found as constituents of biological membranes.

30. The amino group of sphingosine can form an amide bond with a fatty acid carboxyl, to yield a ceramide. In the more complex sphingolipids, a polar “head group" is connected to the terminal hydroxyl of the sphingosine moiety of the ceramide. 

31. Sphingomyelin has a phosphocholine or phosphethanolamine head group. Sphingomyelins are common constituent of plasma membranes. Sphingomyelin, with a phosphocholine head group, is similar in size and shape to the glycerophospholipid phosphatidyl choline.

32. Cholesterol, an important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail. Cholesterol is largely hydrophobic. But it has one polar group, a hydroxyl, making it amphipathic.

33. Structural features of cholesterol (Chol) and cholesteryl esters (Chol-esters) Cholesterol • Four fused hydrocarbon rings (A, B, C, and D, called the "steroid nucleus" • C8 branched hydrocarbon chain attached to C17 • Hydroxyl group at C-3 • Double bond between C-5 and C-6 • Sterols: Steroids with 8 to 10 C in sides chain and hydroxyl group at C-3 • Cholesterol does not occur in plants Cholesteryl esters • Most plasma cholesterol is in an esterified form. • More hydrophobic than Chol • Not in membranes

34. Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase & its hydrophobic ring system adjacent to fatty acid chains of phospholipids. The OH group of cholesterol forms hydrogen bonds with polar phospholipid head groups.

35. Two strategies by which phase changes of membrane lipids are avoided: • Cholesterol is abundant in membranes, such as plasma membranes, that include many lipids with long-chain saturated fatty acids. In the absence of cholesterol, such membranes would crystallize at physiological temperatures. • The inner mitochondrial membrane lacks cholesterol, but includes many phospholipids whose fatty acids have one or more double bonds, which lower the melting point to below physiological temperature.

36. Introduction to lipids Biochemistry II Membrane lipids / Cholesterol Testosterone, the male sex hormone, is produced in the testes. Estradiol, one of the female sex hormones, is produced in the ovaries and placenta. Cortisol and aldosterone are hormones synthesized in the cortex of the adrenal gland; they regulate glucose metabolism and salt excretion. Prednisolone and prednisone are synthetic steroids used as antiinflammatory agents.

37. Anabolic steroids (Athletes) Testosterone • Increase of body mass, strength • Side effects (men)  liver cancer, impotence • Hypercholesterolemia • Breast growth • Side effects (women) increased amount of body hair • Voice deepening • Menstrual irregularities

38. Introduction to lipids Biochemistry II Membrane lipids / Cholesterol

39. Atherosclerosis • Form of ateriosclerosis resulting from the deposition of lipids, primarily TAGs, and Chol, from the blood stream • Chol. is the larger threat • We have to reduce lipid intake • Unstaurated fish and vegetable oil  Loweing of Chol level • Normal Chol level = 200-220 mg/dl • Elevated Chol level should be cotrolled by diet • In extreme cases  cholesterol lowering drungs (pravastatin, lovastatin)

40. Structure Of glycosphingolipids GM2 Sphingomyelin • Glycosphingolipids differ from sphingomyelin in that they do not contain phosphate. • The polar head function is provided by a monosaccharide or oligosaccharide attached directly to the ceramide by an o-glycosidic bond.

41. O H O H H O O H O H O O H O O O H O H O O O H N N H A c ( C H ) C H O H O H O 2 1 6 3 O O O H ( C H ) C 2 1 2 O H O H Neutral glycosphingolipids O b a GalNAc- 1,3-Gal- 1,4- globo- b b Lactosylceramide (Gal- 1,4-Glc- 1,1'-Cer) O O O H O H O H O O H N H N ( C H ) C H ( C H ) C H 2 1 6 3 2 1 6 3 H O H O H O O O ( C H ) C H ( C H ) C H 2 1 2 3 2 1 2 3 O H O H O H O H Glucosylceramide Galactosylceramide • The simplest neutral (uncharged) glycosphingolipids are the cerebrosides (ceramide + galactose or ceramide + glucose). • They serves primarily as an intermediate in the synthesis and degradation of the more complex glycosphingolipids). • The cerebroside are found predominantly in the brain and peripheral nervous tissue. • Ceramide oligosaccharides (or globosides) are produced by attaching additional monosaccharides (including GalNAc).

42. Functions of the Eicosanoids • Eicosanoids participate in many processes in the body: • Inflammatoryresponse that occurs after infection or injury with symptoms such as pain, swelling, and fever. An exaggerated or inappropriateexpression of the normal inflammatory response may occur in individualswho have allergic or hypersensitivity reactions • Contraction of smooth muscles(particularly in the intestine and uterus) • Increase in the excretion of water and sodium by the kidney • Regulation of blood pressure • Regulationof bronchoconstrictionand bronchodilation (modulators)

43. Biosynthesis of the Eicosanoids

44. Cyclooxygenase Pathway: Synthesis of the Prostaglandins and Thromboxanes • 1. Synthesis of PGH2 • Oxidative cyclization of free arachidonic acid by prostaglandin endo-peroxide synthase PGH2 !!!! • PGH2!!!! variety of prostaglandins and thromboxanes • Prostaglandin endoperoxide synthase-2 activities (COX and peroxidase) 2 isoenzymes (COX1 and COX2) [2 O2 molecules] • COX1: (in most tissues): maintenance of healthy gastric tissue, renal homeostasis, and platelet aggregation. • COX2: (inducible in a limited number of tissues) in response to products of activated immune and inflammatory cells.

45. Cyclooxygenase Pathway: Synthesis of the Prostaglandins and Thromboxanes • 2. Inhibition of prostaglandin synthesis • Cortisol (a steroidal anti-inflammatory agent • inhibition of PLA2, COX2 but not COX1. • NSAIDS (nonsteroidal anti-inflammatory agents (e.g. Aspirin) inhibition of COX1 and COX2 damage to the stomach and the kidneys, and impaired clotting of blood, is the basis of aspirin's toxicity. • Specific inhibitors for COX2 (for example, celecoxib1) are designed to reduce pathologic inflammatory processes while maintaining the physiologic functions of COX2.