Lipids

1. Lipids • Introduction : • The lipids are a heterogeneous group of compounds, including fats, oils, steroids, waxes, and related compounds, that are related more by their physical than by their chemical properties. • They have the common property of being • (1) relatively insoluble in water and • (2) soluble in nonpolar solvents such as ether and chloroform.

2. Biochemical importance of lipids: 1. in the diet a. they provide the body with high energy. b. they provide the body with the fat soluble vitamins and the essential fatty acids. c. make the food more delicious. 2. in the human body. a. fats are stored in the adipose tissues to provide the body with energy when needed. b. lipids act as thermal insulator in the subcutaneous tissues and around certain organs. c. combination of lipids and proteins (lipoproteins) serve as the means of transporting lipids in the blood. Knowledge of lipid biochemistry is necessary in understanding many important biomedical areas, eg, obesity, diabetes mellitus, atherosclerosis, and the role of various polyunsaturated fatty acids in nutrition and health

3. Classification of lipids : By structures 1. Simple lipids: a. Fats and oils b. Waxes: 2. Complex lipids: a. Glycolipids b. Phospholipids c. Lipoproteins 3. Precursor and derived lipids: are those compounds that derived from lipids , used for the synthesis of lipids or results from the hydrolysis of lipids. Precursor a. fatty acids b. glycerol Derived lipids a . prostaglandins. b. cholesterol c . steroids

4. Fatty acids Fatty acids: these are aliphatic mono-carboxylic acids (-COOH) which either incorporated in triglyceride (fat) structure or presented as free acid in the circulation ( free fatty acids a transport form in the plasma). Properties of fatty acids . 1. Fatty acids Have the general formula R-(CH2)n-COOH , mostly have straight chain (a few exceptions have branched and heterocyclic chains). In this formula "n" is mostly an even number of carbon atoms (2-34) with a few exceptions that have an odd number. e.gcapric acid CH3- (CH2)4- COOH. 2. majority of fatty acids containing an even number of carbon atoms. 3. the chain of fatty acids could be either saturated ( contain no double bond) or unsaturated ( containing one or more unsaturated double bond). 4.

5. 4. in case of unsaturated fatty acids , geometric isomerism occurs around the axes of double bonds which do not allow rotation ( cisif the acyl chains are on the same side of the bond and trans isomers if on opposite side) . rarely the fatty acids show both the cis and trans isomers where each isomer shows different properties and has its own name . e.goleic acid which is cis isomer and elaidicacid which is the trans isomer of oleic acid. However, the majority of fatty acids show only the cis isomer. Geometric isomerism of ∆9 , 18:1 fatty acids (oleic and elaidic acids). Thus, oleic acid has an L shape, whereas elaidic acid remains "straight." Increase

6. Trans fatty acids are present in certain foods, arising as a byproduct of the saturation of fatty acids during hydrogenation, or "hardening," of natural oils in the manufacture of margarine. Consumption of trans fatty acids is now known to be detrimental to health and is associated with increased risk of diseases including cardio-vascular disease and diabetes mellitus. This has led to improved technology to produce soft margarine low in trans fatty acids or containing none at all. 6. The melting points of fatty acids increase with chain length and decrease according to unsaturation. 7. some of the Fatty acid are essential to the body for normal growth and maintenance and should be supplied with the diet, the essential fatty acids include: Linoleic acidand Arachidonic acid.

7. Fatty acids are classified according to several bases as follows: 1. According to presence or absence of double bonds they are classified into: • A- Saturated Fatty Acids • they contain carbon – carbon single bond ( no doublebonds) with 2-24 or more carbons Palmitic acid). • They are solid at room temperature except if they are short chained. • They have the following molecular formula, CnH2n+1COOH. • Fatty acid chains that contain only carbon-carbon single bonds are referred to as saturated. • Palmitacid:

8. B. Unsaturated fatty acids • These molecules that contain one or more double bond

9. Unsaturated fatty acids may be further subdivided as follows: a. Monounsaturated(monoenoic) acids, containing one double bond. b. Polyunsaturated (polyenoic) acids, containing two or more double bonds. c. Eicosanoids: These are compounds derived from polyenoiceicosa(20-carbon) fatty acids, comprise a series of biochemical compounds of physiological importance e.gleukotrienes (LTs) and prostaglandins (PGs).

11. Naming of fatty acids: majority of the fatty acid can be named by two ways : 1. either by using the systemic name which derived from the corresponding hydrocarbon name ( i.e. it depend on the number of carbon atoms presented in the fatty acid). By this system the terminal (ane) of the hydrocarbon is removed and (anoic) is added in case of saturated fatty acids e.g. octane-------►octanoic acid. Or (enoic) in case of unsaturated fatty acids. e.g. octadecane -------► Octadecenoic acid or by using the common names e.g: Octadecenoic acid = oleic acid hexadecanoicacid = palmitic acid.

12. Naming of fatty acids: 2. Carbon atoms are numbered from the carboxyl carbon (carbon No. 1). The carbon atoms adjacent to the carboxyl carbon (Nos. 2, 3, and 4) are also known as the α, β and γ carbons, respectively, and the terminal carbon is known as the ω- or n-carbon. 3. use the symbol (∆) for indicating the number and position of the double bonds eg, ∆9 indicates a double bond between carbons 9 and 10 of the fatty acid; ω 9 indicates a double bond on the ninth carbon counting from the ω carbon. Oleic acid.n-9 (n minus 9) is equivalent to ω9

13. Classification of lipids : 1. Simple lipids: these areesters of fatty acids with various alcohols and subdivided to : a. Fats and oils : esters of three fatty acids with glycerol (triglyceride) ,fats are the solid form while oils are the liquid form ( at room temperature). b. Waxes: are esters of long chain fatty acids with high molecular weight alcohol rather than glycerol (e.g. of wax : lanolin).

14. 2-Compound LipidsDefinition: • They are lipids that contain additional substances, e.g., sulfur, phosphorus, amino group, carbohydrate, or proteins beside fatty acid and alcohol. • Compound or conjugated lipids are classified into the following types according to the nature of the additional group: • Phospholipids • Glycolipids. • Lipoproteins • Sulfolipids and amino lipids

15. Phospholipids • Phosphoacylglycerolsare triesters of glycerol in which two -ОН groups are esterified with fatty acids and one the third is esterified with phosphofic acid, which in turn is esterified to an alcohol. • Phosphatidylcholines • Phosphatidylethanolamines • Phosphatidylserines • PhosphosphingolipidThey contain sphingosine as an alcohol and are named Sphingomyelinsattached by way of the terminal alcohol group.

16. phospholipids Choline ethanolamine serine

17. phosphatylcholine

18. B-Glycolipids • Definition: They are lipids that contain carbohydrate residues with sphingosine as the alcohol and a very long-chain fatty acid (24 carbon series). • Cerebrosides.They have one galactose molecule (galactosides). • Sulfatides.They are cerebrosides with sulfate on the sugar (sulfated cerebrosides). • Gangliosides.They have several sugar and sugaramine residues.

19. C-Lipoproteins • Lipoproteins are lipids combined with proteins in the tissues. The lipid component is phospholipid, cholesterol or triglycerides. They include: • Structural lipoproteins: These are widely distributed in tissues being present in cellular and subcellular membranes. In lung tissues acting as a surfactant in a complex of a protein and lecithin. In the eye, rhodopsin of rods is a lipoprotein complex. 2. Transport lipoproteins: • These are the forms present in blood plasma. They are composed of a protein called apolipoproteinand different types of lipids. (Cholesterol, cholesterol esters, phospholipids and triglycerides). As the lipid content increases, the density of plasma lipoproteins decreases

20. Lipoproteins • Chylomicrons: They have the largest diameter and the least density. They contain 1-2% protein only and 98-99% fat. The main lipid fraction is triglycerides absorbed from the intestine and they contain small amounts of the absorbed cholesterol and phospholipids. b) Very low-density lipoproteins (VLDL) or pre--lipoproteins: Their diameter is smaller than chylomicrons. They contain about 7-10% protein and 90-93% lipid. The lipid content is mainly triglycerides formed in the liver. They contain phospholipid and cholesterol more than chylomicrons. c) Low-density lipoproteins (LDL) or -lipoproteins: They contain 10-20% proteins in the form of apolipoprotein B. Their lipid content varies from 80-90%. They contain about 60% of total blood cholesterol and 40% of total blood phospholipids. As their percentage increases, the liability to atherosclerosis increases.

21. Lipoproteins d) High-density lipoproteins (HDL) or -Lipoproteins: They contain 35-55% proteins in the form of apolipoprotein A. They contain 45-65% lipids formed of cholesterol and phospholipids . They act as cholesterol scavengers, as their percentage increases, the liability to atherosclerosis decreases. They are higher in females than in males. Due to their high protein content they possess the highest density. e) Albumin-free fatty acids complex:It is a proteolipid complex with 99% protein content associated with long-chain free fatty acids for transporting them.

22. Steroids • Steroids: All steroids have a similar cyclic nucleus resembling phenanthrene (rings A, B, and C) to which a cyclopentane ring(D) is attached. • This nucleus consists of 4 fused non polar rings labeled as A,B,C and D.e .g : cholesterol, bile salts, vitamin D and the steroid hormones ( like cortisol and aldesterone).

23. Cholesterol: • Cholesterol is probably the best known steroid because of its association with atherosclerosis and heart disease . • However, biochemically it is also of significance because it is the precursor of a large number of equally important steroids that include the bile acids, adrenocortical hormones, sex hormones, D vitamins. • Cholesterol has 27 carbon atoms, a hydroxyl group at position 3 , double bond at C5=C6 , two methyl group typically at positions 10 and 13 (constituting C atoms 19 and 18) and side chain at C17

24. cholesterol • Because of the OH group, cholesterol is a steroid alcohol ( sterol) and due to this OH group , cholesterol can be esterified with long chain fatty acids to form cholesterylester. An adult individual contains about 1 gram of cholesterol / Kg body weight , about 25% of it is present in the membrane of the nervous system as a major component of the myelin sheath, cholesterol is also a major component of plasma membrane .

25. Free radicals and lipid peroxidation • What are the free radicals ? • Free radicals generally are atoms, molecules or ions with unpaired electrons. • Different forms of free radicals may presented in our bodies including : reactive oxygen species (ROS) which include(ROO.,RO.,OH.) , lipid radicals and reactive nitrogen species (RNS). • These unpaired electrons are produced during different metabolic reactions, following the ingestion of xenobiotics, following excessive exposure to oxygen,………… . • The unpaired electrons cause radicals to be highly unstable and chemically reactive, when presented in small amounts the body can deal with these radicals easily ( by the activity of anti oxidants) but when presented in large amounts these radicals can attack cell membranes causing damage and even death of these cells, if this abnormal situation continued over long period of time it may progress to serious diseases like cancer.

26. Lipid peroxidation ( auto oxidation of lipids): • is a type of oxidation – reduction reaction, it is a common fate of poly unsaturated fatty acids in both vitro and vivo In vitro oxidation of lipids by oxygen can results in food deterioration (rancidity), • while in vivo lipid peroxidation refers to the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. • lipid peroxidation can results in production of free radicals, the production of free radicals usually initiated by already presented free radicals and results in production of new free radicals (chain reaction).

27. Lipid peroxidation is summarized as in the following: • This process involves three stages: Initiation, Propagation and Termination • Initiation which is the step in which a fatty acid radical is produced. The most notable initiators in living cells are reactive oxygen species (ROS), which combines with a hydrogen atom to make water and a fatty acid radical. • Free radicals usually attack the poly unsaturated fatty acids rather than the saturated fatty acids, this is because of the fact that the presence of double bonds adjacent to a methylene group makes the methylene (C-H) bond weaker and therefore the hydrogen is more susceptible to abstraction, this leaves an unpaired electrons on the carbon forming carbon centered radical.

28. 2. Propagation • The fatty acid ( lipid ) radical is not a stable molecule, so it reacts readily with molecular oxygen, thereby creating a peroxyl-fatty acid radical. This is also an unstable species that reacts with another free fatty acid, producing a different fatty acid radical and a lipid peroxide. This cycle continues, as the new fatty acid radical reacts in the same way . • 3. Termination • When a radical reacts with a non-radical, it always produces another radical, which is why the process is called a "chain reaction mechanism". The radical reaction stops when two radicals react and produce a non-radical species.Theliving organisms have evolved different molecules that speed up termination by catching free radicals and, therefore, protecting the cell membrane. For example of antioxidant are the vitamin E and vitamin C.

29. Also the living organisms have evolved different molecules that speed up termination by catching free radicals and, therefore, protecting the cell membrane. For example of antioxidant are the vitamin E and vitamin C. Anti oxidants are important to protect our bodies from excessive ROS formation otherwise diseases may occur like cancer.

30. antioxidants fall into two classes 1. preventive antioxidants which prevent the formation of ROS for example catalase and glutathione peroxidase( enzymes). 2. Chain reaction breaking antioxidant which interfere with chain progression such as super oxide dismutase and vitamin E which acts in the lipid phase to trap ROO. radicals.

31. Amphipathic lipids: • generally, lipids are water insoluble since they contain a predominance of non polar ( hydrocarbons) groups. • However, fatty acids, phospholipids, bile salts, and to a lesser extent, cholesterol contain polar groups. Therefore, part of the molecule is hydrophobic or water insoluble and part of the molecule is hydrophilic or water soluble Such molecules are described as amphipathic. • When the amphipathic lipids are mixed in water ( aqueous medium), the polar groups (heads) orient themselves towards the aqueous phase while non polar tails oriented towards the opposite directions this leads to the formation of micelles

32. Micellespresented in the intestine (formed from the bile salts in the aqueous medium of the intestine) to facilitate the transport and absorption of lipids from the intestine. Notes: 1. the basic structure of biologic membranes is a bilayer of such amphipathic lipids. 2.emulsions are biphasic system consist of lipid phase mixable with water phase , such system is unstable system and each phase tend to separate from each other, but the addition of amphipathic lipid (which act as surface active agents) will improve the stability of this system

33. Lipid separation different methods can be used for the separation of mixture of different types of lipids including 1. thin layer chromatography (TLC) simple method, rapid and comprehensive method but not very sensitive. 2. solid phase extraction chromatography. 3. high performance liquid chromatography (HPLC).