Lipid Chemistry Lecture 2 PDF

LIPID CHEMISTRY Prepared by: Ass. Prof. Amany Mohamed Salah El-Din Wahb Assistant professor of Medical Biochemistry and Molecular Biology, Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Helwan University Learning object...

LIPID CHEMISTRY Prepared by: Ass. Prof. Amany Mohamed Salah El-Din Wahb Assistant professor of Medical Biochemistry and Molecular Biology, Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Helwan University Learning objectives Describe general classification of lipids. Define the types, structure and functions of fatty acids, compound lipids (phospholipids, lipoproteins, glycolipids) and importance of derived lipids (Cholesterol, Lipid soluble Vitamins). List types of lipoproteins.  Lipids Definition Organic substances relatively insoluble in water but soluble in organic solvents like chloroform, ether and benzene.  Importance of lipids (1) An efficient source of energy (1 gm of fat 9.3 Kcal). (2) Thermal insulators from body heat loss. (3) Organs support and cell membranes structure (Structural components of membranes (phospholipids and cholesterol)). (4) Lipoproteins. (5) Fat-soluble vitamins and essential fatty acids. (6) Cholesterol. (7) Steroid hormones. Importance of lipids  Classification of lipids (A)Simple lipids: (1) Neutral fats (TAG) (2) Waxes (B) Complex or compound lipids: Phospholipids- Glycolipids –Proteolipids (lipoproteins). (C) Derived lipids  Simple lipids A-Neutral Fats and oils ( Triacylglycerol) ( TAG) (Triglycerides) They are called neutral due to absence of ionizable groups in it. The neutral fats are the most abundant lipids in nature. They are the storage form of lipids in body.  Simple lipids-Triacylglycerol (TAG) / Triglycerides (TG) / Neutral fats or oils: They are esters of glycerol with 3 fatty acids. Since the 3 hydroxyl groups of glycerol are esterified, the neutral fats are also called “Triglycerides”. Esterification of glycerol with one molecule of fatty acid gives monoglyceride, and that with 2 molecules gives diglyceride.  Ester bond - COO - Fatty acid + Alcohol ester + H2O R-COOH + R-OH R-COO-R +H2O  GLYCEROL - Glycerol is a trihydric alcohol which can be esterified with one , two or three fatty acids giving mono-, di-, or triglycerides respectively. - Mono and diacylglycerols are of particular significance in the synthesis and hydrolysis of triacylglycerols.  GLYCEROL - Biomedical importance of glycerol: Formation of TAG, the storage form of lipids in body. It is used in pharmaceutical and cosmetic preparations (glycerine). It is used as a vasodilator agent in coronary heart diseases (nitroglycerine). It is used as a laxative. Fatty Acids Fatty Acid Nomenclature Chain length Most fatty acids have an even number of carbons Double bonds Number Location from methyl or carboxyl end Degree of “saturation” H H2 H H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H H H2 H H2 H2 H2 OH Fatty-acid Nomenclature Named according to chain length C18 H2 H2 H2 H2 H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H2 H2 H2 H2 H2 H2 H2 OH Fatty-acid Nomenclature Named according to the number of double bonds C18:0 H2 H2 H2 H2 H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H2 H2 H2 H2 H2 H2 H2 OH Common name: Stearic acid Fatty-acid Nomenclature Named according to the number of double bonds C18:1 H2 H2 H2 H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H2 H2 H2 H H2 H2 H2 OH Common name: Oleic acid Fatty-acid Nomenclature Named according to the number of double bonds C18:2 H2 H2 H H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H2 H H2 H H2 H2 H2 OH Common name: Linoleic acid Fatty-acid Nomenclature Named according to the number of double bonds C18:3 H H2 H H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H H H2 H H2 H2 H2 OH Common name: Linolenic acid Fatty-acid Nomenclature Named according to the location of the first double bond from the methyl end) Omega system (e.g., omega 3, 3) H H2 H H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H H H2 H H2 H2 H2 OH  H2 H2 H2 H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H2 H2 H2 H H2 H2 H2 OH Oleic acid C18:1,∆9 Omega 9 fatty acid H2 H2 H H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H2 H H2 H H2 H2 H2 OH Linoleic: C18:29, 12 Omega 6 fatty acid H H2 H H H2 H2 H2 H2 H3C C C C C C C C C O C C C C C C C C C H2 H H H2 H H2 H2 H2 OH Linolenic acid: C18:39, 12, 15 Omega 3 fatty ac Fatty Acids classification  Fatty Acids classification According to presence or absence of double bonds, A-Saturated Fatty Acids They contain no double bonds. They may be;  Short chain FA (2-10 C) ex. Acetic acid (2c), Propionic acid (3C), Butyric acid (4C).  Long chain FA (more than 10 C) ex. Palmitic acid (16C), Stearic acid (18C). They are solid at room temperature except if they are short chained.  Palmitic & stearic acids are examples of SFAs which are widely distributed in animal fats. Palmitic acid is the commonest FA in human tissues. Examples of food rich in SFAs: Cream, cheese, butter, other whole milk dairy products and fatty meats. Certain vegetable products as coconut oil & palm oil. Biomedical importance of SFAs: High intake of SFAs may lead to increase in plasma cholesterol levels and increase in the incidence of coronary heart diseases. 1-Monounsaturated fatty acids: They have only one double bond. They are present in all animal & vegetable oils (olive oil is a particular rich source). 1-Palmitoleic acid : It is found in all fats. It is C16:1,∆9, i.e., has 16 carbons and one double bond located between carbon number 9 and carbon 10. CH3-( CH2 )5CH = CH-(CH2)7 –COOH 2-Polyunsaturated fatty acids : (Essential fatty acids): Definition: They are essential fatty acids that can not be synthesized in the human body and must be taken in the diet. They are required for normal growth and metabolism Most of the double bonds in USFAs are of the cis type, making the USFAs liquid in room temperature (while the USFAs containing trans-double bonds are solid in room temperature). Source: vegetable oils such as corn oil, linseed oil, olive oil. Cod liver oil and animal fats. Functions of Essential Fatty Acids: They are useful in the treatment of atherosclerosis by help transporting blood cholesterol and triglycerides. They enter in structure of all cellular and subcellular membranes. They are essential for skin integrity and reproduction. Important in preventing and treating fatty liver. Important role in health of the retina and vision. They can be oxidized for energy production. Deficiency of Essential Fatty Acids: Their deficiency in the diet leads to nutrition deficiency disease. Its symptoms include: poor growth and health with susceptibility to infections, dermatitis, decreased capacity to reproduce, impaired transport of lipids and fatty liver. Essential Fatty Acids: 1-Linoleic: C18:29, 12. It is the most important since other essential fatty acids can be synthesized from it in the body. CH3-(CH2)4-CH = CH-CH2-CH=CH- (CH2)7-COOH  Properties of fatty acids (1) Melting point: The melting point of FA increases with the chain length and decreases according to the unsaturation. Thus acetic acid is liquid while palmitic and stearic acids are solids. (2) They are amphipathic molecules i.e. each molecule has: a hydrophilic (polar) head(formed of the COOH a hydrophobic (non-polar) tail(formed of CH).  Types of triglycerides 1-Simple triglycerides: If the three fatty acids connected to glycerol are of the same type ( rare in nature). 2-Mixed triglycerides: If the three fatty acids connected to glycerol are of different types.  Physical Properties of TAG -Solid triacylglycerol are called fats e.g. ghee (butter fat) and margarine (artificial butter). Their solid state is due to their high content of the saturated FA. - Liquid triacylglycerol are called oils e.g. olive, cotton seed, linseed and maize oils. Their liquid state is due to their high content of the unsaturated FA.  Chemical properties of TAG (1) Hydrogenation (Hardening) Addition of hydrogen to the unsaturated fatty acids of vegetable oils, produces the corresponding artificial fats (Margrine). These are now widely used as a substitute to natural fats. 2- Saponification. READ ONLY Alkaline hydrolysis produces glycerol and salts of fatty acids (soaps). Soaps cause emulsification of oily material this help easy washing of the fatty materials O O CH2 O C R1 H2C OH R1 C ONa O O R2 C O C H HO C H + R C ONa 2 O O CH2 O C R3 3 NaOH H2C OH R3 C ONa Triacylglycerol Glycerol Sodium salts of fatty acids (soap) 3-Rancidity Definition: It is a change in the natural properties of the fat leading to the development of unpleasant odor or taste or abnormal color particularly on aging after exposure to atmospheric oxygen, light, moisture, bacterial contamination. Saturated fats resist rancidity more than unsaturated fats that have unsaturated double bonds.  Oxidative Rancidity: This occurs due to oxidative addition of oxygen at the unsaturated double bond of unsaturated fatty acid of oils producing substances e.g., peroxides, aldehydes, ketones and dicarboxylic volatile acids that are toxic and have bad odor. So, saturated fats resist rancidity more than unsaturated fats that have double bonds.  Peroxidation of lipids is responsible for the deterioration of food, destruction of fat- soluble vitamins, particularly vitamin A and also for damage to the tissues in vivo causing cancer, inflammatory disease, atherosclerosis and aging. Hazards of Rancid Fats: The products of rancidity are toxic, i.e., causes food poisoning and cancer. Rancidity destroys the fat-soluble vitamins (vitamins A, D, K and E). Rancidity destroys the polyunsaturated essential fatty acids. Rancidity causes economical loss because rancid fat is inedible. Prevention of rancidity is achieved by: Avoidance of the causes (exposure to light, oxygen, moisture, high temperature and bacterial contamination). By keeping fats or oils in well-closed containers in cold, dark and dry place (i.e., good storage conditions). Addition of anti-oxidants to prevent peroxidation in fat (i.e., rancidity). The most common natural antioxidant is vitamin E (tocopherol).  OUTLINES  Compound lipids classification; A- Phospholipids (Importance , Types; Glycerophospholipids ( Phosphatidic acid- Lecithin- Cephalins- Lipositol) &Sphingophospholipids. B- Glycolipids (classification-Importance) C- Lipoproteins  Derived lipids Cholesterol ( Structure and importance) Vit.D ( Structure and importance)  Compound Lipids Definition:  They are lipids that contain additional substances, e.g., phosphorus, 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: A- Phospholipids B- Glycolipids. C- Lipoproteins  A-Phospholipids Definition: Phospholipids or phosphatides are compound lipids, which contain phosphoric acid group in their structure. Importance: They are present in large amounts in the liver and brain as well as blood. Every animal and plant cell contains phospholipids. The membranes bounding cells and subcellular organelles are composed mainly 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 provide lung alveoli with surfactants that prevent its irreversible collapse.(Lung surfactant is a di-palmitoyl lecithin. Its deficiency leads to neonatal respiratory distress syndrome) They are source of polyunsaturated fatty acids for synthesis of eicosanoids.  Eicosanoids are molecules made by oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, 20 carbon units in length).  Eicosanoids function in diverse physiological systems and pathological processes such as: inflammation, allergy, fever and other immune responses.  There are multiple , including most prominently the prostaglandins. Properties of Phospholipids They are amphipathic molecules i.e. each molecule has: a hydrophilic (polar) head(formed of the phosphate group & the alcohol group) a hydrophobic (non-polar) tail(formed of glycerol or sphingosine& the hydrocarbon chains of the fatty acids).  Classification of Phospholipids according to the type of the alcohol presents; A-Glycerophospholipids: They are regarded as derivatives of phosphatidic acids that are the simplest type of phospholipids and include: Phosphatidic acids. Lecithins Cephalins. Lipositol. B-Sphingophospholipids:Sphingomyelins. A-Glycerophospholipids 1-Phosphatidic acids: 2-Lecithins (phosphatidylcholine) : Structure: Glycerol is connected at C2 with a polyunsaturated fatty acid, at C1 with a saturated fatty acid, at C3 by phosphate to which the choline base is connected. Choline is important in nervous transmission as acetylcholine It is important for formation of lung surfactant (dipalmitoyl-lecithin): Lung surfactant is produced by lung alveolar cells to lower the alveolar surface tension and to improve gas exchange. In premature babies, this surfactant is deficient and they suffer from respiratory distress syndrome. 3-Cephalins (or Kephalins): READ ONLY Definition: They are phosphatidyl-ethanolamine. Structure: Cephalins resemble lecithins in structure except that choline is replaced by ethanolamine. O CH2 O C R1 O R2 C O C H O CH2 O P O CH2 CH2 NH2 Ethanolamine OH HO CH2 CH COOH Serine -Cephalin NH2 HO CH CH COOH Threonine CH3 NH2 4-Lipositol. (phosphatidyl inositol) READ ONLY Structure: They are similar to lecithins or cephalins but they have the cyclic sugar alcohol, inositol as the base. They are formed of glycerol, one saturated fatty acid, one unsaturated fatty acid, phosphoric acid and inositol It plays a role in cell signaling [phosphatidylinositol 4,5 bisphosphate, PIP2]. O CH2 O C R1 O R2 C O C H O OH OH 2 3 CH2 O P O H H H 1 OH 4 OH H H OH 6 5 -Phosphatidylinositol OH H  Cardiolipin (Diphosphatidylglycerol): Cardiolipin consists of 2 molecules of phosphatidic acids connected through one molecule of glycerol. It is an important component of the inner mitochondrial membrane.  B-Sphingophospholipids Sphingomyelins Definition: Sphingomyelins are found in large amounts in brain and nerves Structure: Sphingomyelins differ from lecithins and cephalins in that they contain sphingosine as the alcohol instead of glycerol, they contain two nitrogenous bases: sphingosine itself and choline. Thus, sphingomyelins contain sphingosine base, one long-chain fatty acid, choline and phosphoric acid. To the amino group of sphingosine the fatty acid is attached by an amide linkage. Ceramide This part of sphingomyelin in which the amino group of sphingosine is attached to the fatty acid by an amide linkage. Ceramide Sphingosine Fatty acid OH O CH3 (CH 2)12 CH CH CH CH NH C R1 CH2 Choline O CH3 O P O CH2 CH2 N + CH3 OH CH3 Phosphate Sphingomyelin Glycerophospholipids- Plasmalogen: Plasmalogens: It is found in many tissues as nervous and cardiovascular system: Reduced levels of plasmalogen in nervous tissue are associated with - These are similar to lecithins and cephalins but the fatty acid in position 1 is Alzheimer disease. replaced by unsaturated alcohol the enol form of a fatty aldehyde in an ether linkage.  It is important for activation of blood clotting (platelet activating - Plasmalogens factor constitute about 10% of the phospholipids of brain and muscle. is a plasmalogen).  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). They are present in cerebral tissue, therefore are called cerebrosides Classification: According to the number and nature of the carbohydrate residue(s) present in the glycolipids Cerebrosides.They have one galactose molecule (galactosides). Gangliosides. They have several sugar in addition sialic acids principally neuraminic acid and present in nervous tissues. Cerebrosides (galactolipids): READ ONLY Occurrence: They occur in myelin sheath of nerves and white matter of the brain tissues and cellular membranes. They are important for nerve conductance. Structure: They contain sugar, usually galactose, sphingosine and fatty acid, but no phosphoric acid. Ceramide Sphingosine Fatty acid OH O CH3 (CH 2)12 CH CH CH CH NH C R1 CH2 CH2OH O OH O H Galactose OH H H H H OH Psychosin Cerebroside Cerebrosides (galactolipids): Importance of glycolpids: 1- They are found in plasma membrane. 2- They are important component of myelin sheath. 3- Their carbohydrate part plays a role in cell recognition, e.g. receptors. 4- They are an important constituent of nervous system.  DERIVED LIPIDS Examples Fatty acids Steroids Cholesterol Vitamin D Cholestrol:( The most important sterol) It is made in the liver It has 27C ,a hydroxyl group on C3, a double bond between C5 and C6 and a side chain of 8 carbon atoms. It is found in all animal cells not in plants. In the blood (the total cholesterol amounts about 200 mg/dL of which 2/3 is esterified, chiefly to unsaturated fatty acids while the remainder occurs as the free cholesterol. CH3 CH3 CH3 CH3 CH3 HO Cholesterol References Course Notes: Lectures & labs Essential Book: Lippincott’s Illustrated Biochemistry Reviews (2017), 7th edition Recommended Book: Harper’s Illustrated Biochemistry (2018), 31st edition Periodicals, Web Sites: www.medscape.com, www.ekb.edu.eg