Lipid Chemistry Lecture Notes PDF

Biochemistry of dietary, functional and structural lipids Dr/ Reham Ibrahim Eldosoky Lecturer of Medical Biochemistry Assiut university  Objectives Classification & Biological importance of fat Discuss structure and function of fatty acids, fa...

Biochemistry of dietary, functional and structural lipids Dr/ Reham Ibrahim Eldosoky Lecturer of Medical Biochemistry Assiut university  Objectives Classification & Biological importance of fat Discuss structure and function of fatty acids, fatty alcohols, and their derivatives  Definition of lipids Lipids (or fats) are organic compounds formed mainly from alcohol and fatty acids combined together by ester linkage. Lipids include fats, oils, waxes and related compounds. They are widely distributed in nature both in plants and in animals. O H2O O R CH2 OH HO C R R CH2 O C R + Fatty alcohol Fatty acid Esterase (lipase) ester (lipid) Classification of lipids  I- Simple lipids: They are esters of fatty acids with alcohol. They are called neutral lipids due to absence of ionizable groups (i.e., uncharged). They are classified according to the alcohol present into: Neutral fats: are esters of fatty acids with glycerol (triacylglycerols, or triglycerides).  Waxes: Esters of fatty acids with long-chain alcohols other than glycerol that is mostly monohydric. Cholesterol esters with any fatty acid are waxes. Esters of vitamin A and vitamin D with fatty acid, e.g., palmitic or stearic acid are waxes, too. Ester bond Long-chain alcohol Fatty acid  II- Compound or conjugated lipids: They are esters of fatty acids and alcohols in addition to other groups. They include the following types: Phospholipids (phosphatides): Compound lipids containing fatty acids, alcohol, phosphoric acid and often a nitrogenous base. They are further classified according to the alcohol moiety into: (a) Glycerophospholipids, where the alcohol is glycerol. (b) Sphingophospholipids, where the alcohol is sphingosine.  Glycolipids: Compound lipids containing fatty acids, carbohydrate and sphingosine, but not phosphoric acid nor glycerol. Lipoproteins: Compound lipids composed of a lipid part associating by secondary bonds with proteins as plasma and membranous lipoproteins. Other compound lipids: include: Sulfolipids: containing sulfur. Aminolipids: containing amino acids.  III- Derived Lipids: They are products of hydrolysis of simple and compound lipids and/or their derivatives that still possess the general characteristics of lipids. They include: Fatty acids, monoglycerides and aldehydes. Alcohols including glycerol. steroids and hormonal derivatives of vitamin D. Eicosanoids (prostaglandins, leukotrienes and thromboxanes). Ketone bodies.  Biological Importance of Lipids They have a high-energy value (25% of body needs) and they provide more energy per gram than carbohydrates and proteins. Supply the essential fatty acids that cannot be synthesized by the body. Supply the body with fat-soluble vitamins (A, D, E and K). They are important constituents of the nervous system.  Tissue fat “constant fat” is an essential constituent of cell membrane and nervous system. It is mainly phospholipids in nature that are not affected by starvation.  Stored lipids “depot fat” are stored mainly in adipocytes. It is mainly triglycerides in nature and acts as: - A store of energy. - A pad for the internal organs to protect them from outside shocks. - A subcutaneous thermal insulator against loss of body heat.  Lipoproteins, which are complex of lipids and proteins, are important cellular constituents that present both in the cellular and subcellular membranes. Cholesterol enters in membrane structure and is used for synthesis of adrenal cortical hormones, vitamin D3 and bile acids. Understanding biochemistry of lipids provide bases for dealing with diseases such as obesity, atherosclerosis, lipid-storage diseases, respiratory distress syndrome.  Fatty Acids Definition: Fatty acids are aliphatic mono-carboxylic acids that are mostly obtained from the hydrolysis of natural fats and oils. They have the general formula R-(CH2)n-COOH and 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 or even zero in acetic acid. Fatty acids can be classified as follows: I) Saturated, i.e., they contain no double bonds with 2-24 or more carbons. They are solid at room temperature except if they are short chained. They have the following molecular formula, CnH2n+1COOH. Examples are butyric, palmitic and stearic acids. II) Unsaturated, i.e., they contain one (monounsaturated, CnH2n-1COOH) or more double bonds (polyunsaturated, CnH2n- more than 1COOH). Some fatty acids may contain hydroxyl or ketogroups, few cyclic fatty acids are known. Polyunsaturated fatty acids (Essential fatty acids polyenoic or polyethenoid): Definition: They are essential fatty acids that can not be synthesized in the human body (due to lack of enzymes that can form more than one double bond) and must be taken in adequate amounts in the diet. They are required for normal growth and metabolism. They are liquids at room temperature.  Function 1. They are useful in the treatment of atherosclerosis by help the transport of blood cholesterol and lowering it. 2. The hormone-like eicosanoids are synthesized from them. 3. They participate in the structure of all cellular and subcellular membranes and the transporting plasma phospholipids. 4. They are essential for skin integrity, normal growth and reproduction. 5. They have an important role in blood clotting (intrinsic factor). 6. Important in preventing and treating fatty liver. 7. They have an important role in the health of the retina and vision. 8. They can be oxidized for energy production.  Deficiency: Their deficiency in the diet leads to nutritional deficiency disease. Its symptoms include: poor growth and health with susceptibility to infections, dermatitis, decreased capacity to reproduce, impaired transport of lipids, fatty liver, and lowered resistance to stress. Source: vegetable oils such as corn oil, linseed oil, peanut oil, olive oil, cottonseed oil, soybean oil and many other plant oils, cod liver oil and animal fats. Examples: Include: Linoleic: C18:29, 12. CH3-(CH2)4-CH=CH-CH2-CH=CH-(CH2)7-COOH -Linolenic acid: C18:39, 12, 15, in corn, linseed, peanut, olive, cottonseed and soybean oils. -Linolenic acid: is a positional isomer for -Linolenic acid, C18:36, 9, 12.  Arachidonic acid: C20:45, 8, 11, 14. It is an important component of phospholipids in animal and in peanut oil. It is synthesized in the body from linoleic acid which in turn metabolized into prostaglandins. Clupandonic acid: 22:57, 10, 13, 16, 19. It is present in fish oils and brain phospholipids. III- Hydroxy fatty acids -They contain one or more hydroxyl groups, e.g., ricinoleic (18:19, hydroxy at C12), dihydroxy-stearic acids (18: dihydroxy at C9 and C10), both are found in castor oil, oxynervonic (24:115, hydroxy at C2), cerebronic (24: hydroxy at C2) found in brain glycolipids. OH | CH3-(CH2)5-CH- CH2-CH=CH-(CH2)7-COOH Recinoleic acid CH3-(CH2)7—CH-- CH-(CH2)7-COOH | | OH OH Dihydroxy-stearic IV- Branched chain fatty acids: - There are fatty acids with branched chains such as phytanic acid that is a by-product of chlorophyll catabolism in human and animal that is present in butter. If it is not oxidized in the body it will be toxic (Refsum’s disease).  Fatty Acids Saturated Unsaturated Hydroxy FA Branched chain FA Short chain Long chain Monounsaturated Polyunsaturated 2-10 c More than 10 c Palmitoleic acid Linoleic Oleic acid -Linolenic acid Volatile Non-volatile Nervonic acid -Linolenic acid Arachidonic acid Clupandonic acid  Alcohols Alcohols associated with lipids include: glycerol, cholesterol and higher alcohols (e.g., cetyl alcohol, mericyl alcohol, dolicols…etc.) Glycerol: - It is a trihydric alcohol (i.e., containing three OH groups) and has the popular name glycerin. It is synthesized in the body from glucose. On heating with sulfuric acid or KHSO4 (dehydration), it gives acrolein (acryl aldehyde) that has a bad odor. This reaction is used for detection of free glycerol or any compound containing glycerol. CH2 OH 2 H2O CHO HO CH CH Heating, KHSO4 CH2 OH CH2 Glycerol Acrolein  On esterification with fatty acids it gives: Monoglyceride or monoacyl-glycerol: one fatty acid + glycerol. Diglyceride or diacyl-glycerol: two fatty acids + glycerol. Triglyceride or triacyl-glycerol: three fatty acids + glycerol. It has a nutritive value by conversion into glucose and enters in structure of phospholipids. Uses of Glycerol: Glycerol enters in pharmaceutical and cosmetic preparations (hygroscopic). Nitroglycerin (glyceryl trinitrate) is used as a vasodilator especially for the coronary arteries, thus it is used in treatment of angina pectoris. Glycerol is used in treatment of glaucoma (increased intraocular pressure) due to its ability to dehydrate the tissue from its water content. CH2 ONO2 O2NO CH CH2 ONO2 Trinitroglycerine Sphingosine: It is the alcohol present in sphingolipids. It is synthesized in the body from serine and palmitic acid. It is not positive with acrolein test. OH CH3-(CH2)12-CH CH CH CH NH2 CH2OH Sphingosine  Objectives ❖Discuss Structure and function of phospholipids, glycolipids with special emphasis on cell membrane ❖Discuss Structure and function of lipoproteins  a) Phospholipids Structure: Phospholipids are compound lipids, which contain alcohol, fatty acids, nitrogenous base and phosphoric acid group. There are two classes of phospholipids according to the type of the alcohol present. Glycerophospholipids (contain glycerol as alcohol) - Lecithins - Cephalins - Cardiolipin - Inositides - Plasmalogens Sphingophospholipids (contain sphingosine as alcohol) - Sphingomyelins  Functions: In association with proteins, phospholipids form the structural components of membranes and regulate membrane permeability. The subcellular organelles (endoplasmic reticulum, Golgi apparatus, mitochondria, nucleus, and lysosomes) are composed mainly of phospholipids. Thus, the transfer of substances through these membranes is controlled by properties of phospholipids.  They are important components of the lipoprotein coat essential for secretion and transport of plasma lipoprotein complexes. Thus, they are lipotropic agents that prevent fatty liver. Myelin sheath of nerves is rich with phospholipids. Important in digestion and absorption of neutral lipids and excretion of cholesterol in the bile. They have important functions in blood clotting and platelet aggregation (cephalin).  They provide lung alveoli with surfactants that prevent its irreversible collapse ( lecithin or dipalmitoyl phosphatidyl choline). They have an important role in signal transduction across the cell membrane (precursor for second messenger) (Phosphatidyl Inositol). They are source of polyunsaturated fatty acids for synthesis of eicosanoids  b) Glycolipids structure: They are lipids that contain carbohydrate residues with sphingosine as the alcohol and a very long-chain fatty acid (24 carbon series). They are present in cerebral tissue, therefore are called cerebrosides. They are also referred as sphingogalactolipids or galactosides Ceramide Sphingosine Fatty acid OH O CH3 (CH2)12 CH CH CH CH NH C R1 CH2 CH2OH O OH O H Galactose OH H H H H OH Psychosin  Classification: According to the number and nature of the carbohydrate residue(s) present in the glycolipids, the following types exist: Cerebrosides. They have one galactose molecule (galactoside) or it may have one glucose (glucoside) or one lactose (lactoside) + ceramide. Sulfatides. They are cerebrosides with sulfate on the sugar (sulfated cerebrosides) + ceramide Globosides: two or more hexoses + ceramide. Gangliosides. They have several sugar and aminosuger residues + ceramide + sialic acid.  Functions: Are an essential part of cell membranes Glycolipids (globosides) determine the blood group of the individuals. Gangliosides transfer biogenic amines across the cell membrane and act as a cell membrane receptor for cholera and tetanus toxins. This helps immune system to destroy and clear pathogen from body.  C- Lipoproteins What is lipoproteins? Lipoproteins are spherical macromolecular complexes of lipids and specific protein called apo-protein.  What are the functions of lipoproteins? 1- They keep water insoluble lipids in solution of aqueous plasma. 2- Provide mechanism for transporting their lipid components to and from the tissue. Name the classes of lipoproteins? 1- Chylomicrons 2- Very low density lipoproteins (VLDL) 3- Low density lipoprotein (LDL or -lipoprotein) 4-High density lipoprotein (HDL or -Lipoprotein) 5-Free Fatty Acid – Albumin complex  a) Chylomicrons: They contain 1-2% protein only and 98-99% fat. Function: They carry triglyceride, cholesterol ester and phospholipids from the intestine to the peripheral tissues. b) Very low-density lipoproteins (VLDL) or pre--lipoproteins: They contain about 7-10% protein and 90-93% lipid. Function: It carries triglycerides from the liver to extrahepatic tissues. 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. Function: It carries cholesterol to various tissues. As their percentage increases in the blood, the liability to atherosclerosis increases. d) High-density lipoproteins (HDL) or -Lipoproteins: They contain 40% proteins in the form of apolipoprotein A. They contain 60% lipids formed of cholesterol (40% of total blood content) and phospholipids (60% of total blood content). They act as cholesterol scavengers, as their percentage increases, the liability to atherosclerosis decreases. e) Albumin-free fatty acids complex: It is a proteolipid carried on plasma albumin with 99% protein content associated with long-chain free fatty acids (1%) for transporting them.