Lipid Chemistry. Presented By. Ayman Elsamanoudy Salwa Abo El-khair

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2 Lipid Chemistry Presented By Ayman Elsamanoudy Salwa Abo El-khair 4

3 Objectives: 1. By the end of this chapter the student should be able to: define lipids. describe the biological importance of lipids. point out basic lipid chemistry. classify lipids. explain the chemistry and main function of simple, compound and derived lipids. 2. By the end of this chapter the student should be able to apply biochemical knowledge on analyzing biochemical bases of the diseases through case study. 3

4 Compound Lipids

5 Compound Lipids Compound (conjugated) lipids are lipids conjugated with other substances. They include: Phospholipids : (lipid+ phosphoric acid + nitrogenous base). Glycolipids :(lipid + carbohydrate). Sulpholipids :(lipids + sulphate). Lipoproteins :(lipid + protein).

6 Phospholipids They are a group of compound lipids formed of: Alcohol &Fatty acids + Phosphoric acid + Nitrogenous base (may be). They are classified according to the alcohol into: Phosphoglycerides Sphingomyelin

7 Phosphoglycerides In which nitrogen phosphorous ratio (N/P ratio =1) is 1 i.e. they contain one nitrogen and one phosphate. Sphingomyelin in which N/P ratio is 2 i.e. it contains 2 nitrogen and one phosphate.

8 A- Phosphoglycerides Phosphoglycerides are a group of phospholipids containing glycerol with N/P ratio = 1. They include: Phosphatidic acid Lecithin, Cephalins, Phosphatidyl inositol Plasmalogen Cardiolipin.

9 1- Phosphatidic acid It is phosphoric acid ester of diglycerides. Structure: Glycerol. Saturated fatty acid, attached to α carbon of glycerol by ester bond. Unsaturated fatty acid, attached to β carbon of glycerol by ester bond. Phosphoric acid attached to α carbon of glycerol by ester bond. Function of phosphatidic acid It is an intermediate compound in biosynthesis of other phosphoglycerides and triglycerides

10 2- Lecithin It is phosphatidyl choline. It is formed of: Glycerol. Saturated fatty acid, Unsaturated fatty acid, Phosphoric acid, Choline attached to phosphoric acid by ester bond. This means :phoshatidic acid + choline base

11 Function of lecithin 1. It is the most abundant phospholipids in the cell membrane. 2. It acts as a lipotropic factor (substances that prevent accumulation of lipids in the liver). 3. Dipalmityl lecithin acts as Lung surfactant (substances that line the lung alveoli forming a layer at the interface of fluid lining the alveoli and air inside alveoli preventing lung collapse).

12 Respiratory Distress Syndrome (RDS) Incidence :In premature infants. Causes : the lung alveoli don t secrete sufficient amount of lecithin. Effect : lung collapse. 12

13 Lysolecithin Snake venom contains lecithinase enzyme, which removes the unsaturated fatty acid from lecithin forming lysolecithin. Lysolecithin is a strong surface- active substance that has a marked haemolytic action causing haemolysis of the red blood cells.

14 Lysolecithin

15 Cephalins They are phosphatidyl ethanolamine & phosphatidyl serine Structure They are formed of: Glycerol. Saturated fatty acid Unsaturated fatty acid, Phosphoric acid. Ethanolamine or serine.

16 Phosphoglycerides 3- Cephalins phosphatidyl ethanolamine CH O COR1 CH CH CH CH O O O O COR2 HPO4 CH2 CH2 NH2 HO CH2 CH2 NH2 Ethanolamine COR1 COR2 CH O HPO4 CH2 CH COOH CH2 CH COOH phosphatidyl serine NH2 OH HO NH2 Serine

17 Phosphatidyl-serine 17 Phosphatidyl-ethanolamine

18 Function of cephalins They have a role in blood coagulation. They accelerate blood clotting because they share in the structure of thromboplastin, which is essential for blood clotting.

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20 4- Phosphatidyl inositol (lipoinositol). Structure It is formed of: Glycerol. Saturated fatty acid, Unsaturated fatty acid, Phosphoric acid Inositol, which is a cyclic alcohol derived from glucose.

21 R 2 O CH 2 O C R 1 O C O C H O CH 2 O P OH O H -Phosphatidylinositol 1 OH H H OH OH H OH H 5 H 4 OH 21

22 Function of phosphatidyl inositol: It is found in brain tissue. It has a role in mechanism of hormone action. on hydrolysis by phospholipase C enzyme, it gives compounds that acts as second messengers in hormone action e.g. diacyl glycerol (DAG) and inositol triphosphate (IP3).

23 5- Plasmalogens: Structure It is formed of: Glycerol. (unsaturated alcohol) at α position. (fatty aldehyde in the enol form) Unsaturated fatty acid at β position. Phosphoric acid. Nitrogenous base, which may be choline, ethanolamine or serine. SO, They are lecithin or cephalin in which the fatty acid attached to α carbon is replaced by unsaturated alcohol.

24 Function of plasmalogens They are present in cardiac muscle, skeletal muscles and brain.

25 6- Cardiolipin It is a diphosphatidyl glycerol formed of 2 phosphatidic acids attached together by glycerol. R 2 O C O O CH 2 O C R 1 CH 2 O C H O CH 2 O P O OH H C OH CH 2 R 4 C O CH 2 O Cardiolipin OH P O CH 2 O H C O C O R 3

26 Structure of Cardiolipin It is formed of: 3 glycerol molecules. 2 saturated fatty acids. 2 unsaturated fatty acids. 2 molecules of phosphoric acid. Functions of cardiolipin Cardiolipin is present in heart muscle. It is used as antigen for detection of syphilis.

27 B- Sphingomyelins Sphingomyelin is a phospholipids with N/P ratio = 2. sphingomyelin contains sphingosine base (18 C). It is called Sphingol ; long chain unsaturated amino alcohol) instead of glycerol.

28 Sphingolipids

29 Ceramide It is formed of sphingosine base to which fatty acid is attached by amide linkage.

30 Structure of sphingomyelin Sphingosine base. Unsaturated fatty acid (to the amino group of sphingosine by amide link). Phosphoric acid (to the primary alcoholic group of sphingosine by ester bond ). Choline base attached to phosphoric acid by ester bond.

31 Sphingomyelin

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33 Function sphingomelin It is abundant in the nervous system in the myelin sheath. It is present to lesser extent in liver, spleen and bone marrow.

34 N.B: Nimann Pick disease It is a disease caused by deficiency of sphingomelinase enzyme, which catabolizes sphingomyelin. This leads to accumulation of large amounts of sphingomelin in liver, spleen and brain.

35 Alcohol Fatty acids Phosphate group Nitrogenous Base N/P ratio Acroline test Types 35 phosphoglycerides Glycerol -2FA -(at α position is saturated & at β is unsaturated ) -linked by ester bond One Differ according to the type 1 Positive Phosphatidic acid,lecithen, cephalines,plasmalogen and cardiolipin Sphingophospholipids Sphingosine base (sphingol alcohol) -One -( usually long unsaturated ) -linked by amide link One Choline base 2 Negative Sphingomyeline

36 Lipid Chemistry Presented By Ayman Elsamanoudy Salwa Abo El-khair 5

37 Glycolipids They are compound lipids (carbohydrates +lipids). They contain sphingosine base They include cerebrosides and gangliosides. 1- Cerebrosides They are called cerebrosides because they are present mainly in the brain and nerves.

38 Cerebrosides Structure Sphingosine base. Long chain fatty acid attached to the amino group of the sphingosine base by amide linkage. Carbohydrate usually galactose but may be glucose.

39 According to the fatty acid present, Cerebrosides are classified into: kerasin Cerebron nervon Oxynervon FA Lignoceric acid Cerebronic acid Nervonic acid Hydroxynervonic acid Number of its C- atoms Degree of saturation Saturated Saturated Monounsaturated Monounsaturated Hydroxyl group Non hydroxy FA hydroxy FA Non hydroxy FA hydroxy FA 39

40 Functions of cerebrosides 1. They are present mainly in the nervous tissues i.e. brain and nerves. - They act as electric insulators of nerve impulses. 2. Also, they are present in spleen, liver, adrenal gland, kidney and lungs.

41 2- Gangliosides These are the most complex glycolipids. Structure Sphingosine base. Long chain fatty acid. One glucose molecule. 2 galactose molecules. N-acetyl galactosamine. N-acetyl neuraminic acid (siailic acid; NANA). Function Lipid part CHO part Gangliosides are present in high concentration in brain. They act as receptors at cell membrane.

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43 Sulpholipids They are cerebrosides containing sulphate group attached to C3 of galactose. Structure: Sphingosine base. Long chain fatty acid (attatched to the amino group of the sphingosine base). Carbohydrate usually galactose but may be glucose. Sulphate group (attatched to C3 of galactose).

44 Structure of supholipids Function They are present in brain and nervous tissues.

45 Structure of galactosylceramide (galactocerebroside, R = H), and sulfogalactosylceramide (a sulfatide, R = SO 4 2- )

46 Lipoproteins These are compound lipids formed of : lipid part (triglycerides, cholesterol or phospholipids) & protein part (α or β globulin). Function of lipoproteins: In the structure of cell membrane. Lipid transport in the blood (Lipids are insoluble in water). Lipids bind to protein to make lipoproteins water-soluble to be transported in the blood.

47 Lipoproteins Each contains different kinds and amounts of lipids and proteins The more protein, the higher the density The more lipid, the lower the density Each has different function

48 Hydrophobic lipids Amphiphilic lipids

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50 Structure of lipoprotein Hydrophobic lipids (TG, CE) in the core Amphiphilic lipids (C, PL) and proteins on the surface

51 Separation of lipoproteins Lipoproteins can be separated by: 1- Ultracentrifugation In NaCl solution, lipoproteins are separated by ultracentrifugation, as they differ in the degree of floatation, into : chylomicrons, VLDL, LDL and HDL. 2- Electrophoresis As they differ in migration rate due to differences in molecular weight and charge, lipoproteins are separated into : chylomicrons, pre β, β and α lipoproteins. 3- Chromatography

52 According to ultracentrifugation -Chylomicrons, -Very low-density lipoproteins -Low-density lipoproteins -High-density lipoproteins According to electrophoresis: -Chylomicrons, -Pre-β lipoproteins, -β lipoproteins, -α lipoproteins.

53 Lipoproteins Anode + Cathode --- α lipoproteins Pre-β lipoproteins β lipoproteins Chylomicrons (HDL) (VLDL) (LDL)

54 Lipoproteins Site of synthesis Structure Chylomicrons VLDL Small intestine Liver Mainly triglycerides, small amount of cholesterol, phospholipids and protein Mainly triglycerides, greater amount of cholesterol, phospholipids and protein

55 Lipoproteins LDL HDL Site of synthesis Liver Blood Liver Structure Mainly cholesterol and good amount of proteins, phospholipids and triglycerides Mainly proteins and phospholipids, small amount of cholesterol and little amount of triglycerides

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57 Chylomicron VLDL LDL HDL Size Largest Large Small Smallest Rate of floatation Electrophoresis Highest High Low Lowest Do not migrate because of their high content of triglycerides (have high molecular weight and no charges). Migrate after β globulin Migrate with β globulin Migrate with α globulin

58 Chylomicron Function Transport exogenous triglycerides from the small intestine to tissues. LDL Function Transport cholesterol from the liver to tissues. VLDL Transport endogenous triglycerides from the liver to tissues. HDL Retrograde transport of cholesterol from the tissues to liver. Transport phospholipids from the liver to tissues.

59 Chylomicron VLDL LDL HDL Site of synthesis Small intestine Liver Blood Mainly in Liver Size Largest Large Small Very small Structure Mainly triglycerides, small amount of cholesterol, phospholipids and protein Principally triglycerides, greater amount of cholesterol, phospholipids and protein Mainly cholesterol and appreciable amount of proteins, phospholipids and triglycerides Mainly of proteins and phospholipids, small amount of cholesterol and little amount of triglycerides Functions Transport exogenous triglycerides from the small intestine to the tissues. Transport endogenous triglycerides from the liver to the tissues Transport cholesterol from the liver to the tissues. Transport cholesterol from the tissues to the liver (reverse cholesterol transport Rate of floatation Electrophore 59 Highest Do not migrate High Migrate before β Low Migrate with β Lowest Migrate with α

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61 Activity 1- Give the hydrolytic products of the followings: 1-Lecithen 2- Cephalins 3- Cardiolipis 2-Compare between each of the followings : 1-Phosphoglycerides& sphingophospholipids 2-Chylomicron and HDL. 3- cerbrosides and gandliosides 3- enumerate the types of lipoproteins & mention the main function 61 of each of them

62 4-Enumerate: 1-lipids that contain choline base. 2- lipids that contain sphingol alcohol. 3-lipids that contain galactose sugar. 4- Methods of separation of lipoproteins 5- what is the type of bond in each of the following: 1- TAG 2-Ceramide. 62

63 Choose the best correct nswer Ceramide is a constituent of the following EXCEPT: a) cerebroside b) sulfatides c) sphingomyelins d) lecithen 63

64 GREAT THANKS Ayman Elsamanoudy Salwa Abo El-khair 11/17/2014 Ahmed A.Albadry 64