Lipid Chemistry 2023 PDF

LIPID CHEMISTRY By PROF (MRS) J.E IKEKPEAZU  INTRODUCTION The lipids are a heterogeneous class of cellular organic biomolecules that differ widely in terms of chemical composition. They are relatively insoluble in water and other polar solvents while bein...

LIPID CHEMISTRY By PROF (MRS) J.E IKEKPEAZU  INTRODUCTION The lipids are a heterogeneous class of cellular organic biomolecules that differ widely in terms of chemical composition. They are relatively insoluble in water and other polar solvents while being highly soluble in non-polar organic solvents such as ether, chloroform and benzene. They are actually or potentially related to fatty acids and are utilized by the living cells. Certain lipids contain ionized groups, but the bulk of any lipid molecule is non-polar. The lipids include fats and oils, waxes and related compounds. The primary building blocks in human lipids are fatty acids and alcohol which may be glycerol, sphingosine and sterols.  BIOMEDICAL IMPORTANCE OF LIPIDS They have high energy value and serve as an efficient source of energy, both directly and potentially when stored in the adipose tissue (triacylglycerol). are structural component of the cell membrane occurring both in the cell membrane and in the intracellular organelles like the mitochondria within the cytoplasm. The major part of the lipid of biological membrane consists of mainly phospholipids in addition to glycolipids and cholesterol. serve as thermal insulators in the subcutaneous tissues (this accounts for our being warm- blooded).  BIOMEDICAL IMPORTANCE OF LIPIDS CONTD. when laid around vital organs, fatty tissues serve as protection against mechanical injury. act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves. Fats of natural foods contain vitamins (fat- soluble vitamins: A, D, E and K) and essential fatty acids , which are made available from their consumption. As lipoproteins (combinations of fat and protein) they serve as the means of transporting lipids in the blood. Serve as metabolic regulators (steroid hormones) prostaglandins and leukotrienes.  BIOMEDICAL IMPORTANCE OF LIPIDS CONTD. Act as surfactants, detergent and emulsifying agents(amphipathic lipids) Act as second messengers in hormone action eg phosphatidyl inositol They give shape and contour to the body. CLINICAL IMPORTANCE OF LIPIDS lipid chemistry and metabolism is important because it helps us to understand many current biomedical areas of interest in lipids such as obesity, atherosclerosis, diabetes mellitus, fatty liver and the role of polyunsaturated fatty acids in nutrition and health.  CLASSIFICATION OF LIPIDS The following classification of lipids is mainly based on that proposed by Bloor: A). SIMPLE LIPIDS: These are esters of fatty acids with various alcohols. Fats: This group, also called neutral fats are esters of fatty acids with glycerol. A fat in the liquid state is known as oil. Waxes: These are esters of fatty acids with higher molecular weight monohydric alcohols.  CLASSIFICATION OF LIPIDS CONTD. B). COMPOUND LIPIDS: This class, also known as complex lipids are esters of fatty acids and alcohol, containing other groups in addition to the alcohol and a fatty acid. Phospholipids: These are lipids containing in addition to fatty acids and an alcohol, a phosphoric acid residue. They also have nitrogen containing bases and other substituents. The phospholipids are further classified into the glycerophospholipids and sphingophospholipids. In the glycerophospholipids, the alcohol is glycerol, while in the sphingophospholipids, it is sphingosine. Glycerphospholipids include lecithin, cephalin, cardiolipin, phosphatidyl serine and phosphatidyl inositol while an example of sphingophospholipid is sphingomyelin.  Glycolipids: These are compounds of the fatty acids and alcohol with carbohydrate and may contain nitrogen but no phosphoric acid. Examples are cerebrosides and gangliosides Other Compound Lipids: Such as sulfolipids, aminolipids and lipoproteins (chylomicrons, HDL, VLDL, and LDL)may be placed in this category.  CLASSIFICATION OF LIPIDS CONTD. C). DERIVED LIPIDS: These are substances derived from the above groups(simple and compound lipids) by hydrolysis: They include fatty acids (both saturated and unsaturated), glycerol, steroids and sterols, eicosanods(prostaglandins, thromboxanes and leukotrienes), alcohols in addition to glycerol and sterols, fatty aldehydes and ketone bodies. D)Miscellaneous lipids: these posses characteristics of lipids eg squalene and carotenoids FATTY ACIDS: Nomenclature, Classificaton and Functions Fatty acids are obtained from the hydrolysis of fats. Fatty acids in natural fats usually contain I. an even number of carbon atoms II. are straight chain derivatives III. may be saturated or unsaturated. iv. All fatty acids have a single carboxyl group at the end of a hydrocarbon chain, which makes them weak carboxylic acids. v. General molecular formular: R-COOH where R represents an Alkyl group  CLASSIFICATION Carbon Chain lenght: Fatty acid may be of short chain lenghts(C2 to C6); Medium chain(C8 to C12 or 14 ); Long chain (C12 to C24); and Very long chain(more than C24) The total carbon chain: may have odd or even number but usually of even number. Nature of chain: May be saturated, unsaturated, branched(fatty acids from natural sources are mainly of straight chain) or hydroxy. Synthesis in the body: may be essential or non- essential.  NOMENCLATURE Fatty acids are named after the hydrocarbon with the same number of carbon atoms, -oic being substituted for the final e in the name of the hydrocarbon. Saturated acids end in –anoic while the unsaturated end in - enoic. Carbon atoms are numbered from the carboxyl carbon (carbon No.1). The carbon atom adjacent to the carboxyl carbon (No. 2) is also known as the -carbon. Carbon atom No. 3 is the β-carbon the end methyl carbon is known as the -carbon(omega carbon). Various conventions are in use for indicating the number and position of the double bonds in unsaturated fatty acids e.g. Δ9 indicates a double bond between carbon atoms 9 and 10 of the fatty acids.  STRUCTURE AND NOMENCLATURE OF FATTY ACIDS No of Carbons Common Name General Name Structure 4 Butyric Acid Tetranoic CH3(CH2)2COOH 6 Caproic Acid Hexanoic CH3(CH2)4COOH 8 Caprylic Acid Octanoic CH3(CH2)6COOH 10 Capric Acid Decanoic CH3(CH2)8COOH 12 Lauric Acid Dodecanoic CH3(CH2)10COOH 14 Myristic Acid Tetradecanoic CH3(CH2)12COOH 16 Palmitic Acid Hexadecanoic CH3(CH2)14COOH 18 Stearic Acid Octadecanoic CH3(CH2)16COOH 20 Arachidic Acid Eicosanoic CH3(CH2)18COOH  Common unsaturated fatty acids One double bond Omega series 18C Oleic 9-octadecenoic CH3(CH2)7CH=CH(CH2)7COOH ω9 Two double bonds 18C Linoleic 9, 12-octadecadienoic CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH ω6 Three double bonds 18C Linolenic 9, 12, 15, Octadecatrienoic CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH ω3 Four Double Bonds 20C Arachidonic 5, 8, 11, 14 Eicosatetraenoic CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH  Fatty acids with a double bond on carbon 3 counting from the omega carbon are called the omega-3 or ω3 fatty acids. Those with double bonds on carbon 6 and 9 counting from the omega carbon are called omega-6(ω6) and omega-9 (ω9) fatty acids respectively. The two abundant saturated fatty acids in humans are palmitic acid (C16) and stearic acid (C18). Oleic acid (C18:1) and palmitoleic acid (C16:1) compose the bulk of the monounsaturated, or monoenoic fatty acids in humans. Both have a carbon-carbon double bond between carbons 9 and 10.  Polyunsaturated fatty acids (PUFA), or polyenoic acids include linoleic acid (C18:2) with two double bonds; linolenic acid (C18:3) with three and arachidonic (C20:4) with four double bonds. Linoleic and linolenic acids are termed essential fatty acids because they cannot be synthesized by mammals. Arachidonic acid can be produced in humans from linoleic acid and only becomes essential in the absence of linoleic acids. Polyunsaturated fatty acids are the precursors for some physiologically important compounds such as the prostaglandins, the thromboxanes and leukotrienes. These are synthesized from Eicosatetraenoic acid ie Arachidonic acid.  Note: sources of linoleic acid include: Corn oil, peanut oil, cotton seed oil, soybean oil, many plant oils and meat/eggs. Sources of linolenic acids include: Walnutoil, canola oil(rapeseed oil), fish liver, seafood/fatty fish and soybean oil.  Functions of Essential fatty acids(EFA) 1. Synthesis of prostaglandin, prostacyclins, thromboxanes and leukotrienes 2. Sythesis of two other Ѡ-3 PUFA from linoleic acid (eicosapentaenoic acid,EPA and Docosahexaenoic acid,DHA) which are required for proper develpment and functioning of the brain and nervous tissues. 3.Maintenance of structural integrity(formation of healthy cell membranes): structural integrity of mitochondrial membrane; note that Arachidonic acid is about 5 to 15% of fatty acids in phospholipids. 4. Lipoproteins formation 5. Prevents fatty liver(deposition of TAG in the liver) 6. Antiatherogenic effect(PUFA is cardioprotective). Essential fatty acids(arachidonic acid) increase esterification and excretion of cholesterol, thereby lowering the cholesterol level.  ESSENTIAL FATTY ACID DEFICIENCY(phrynoderma or toad skin) It is characterised by horny eruptions on the skin(limbs, back, buttocks); scaly skin,eczema(in children),loss of hair and poor wound healing. Impaired lipid transport and fatty liver may occur Decreases efficiency of biological oxidation. NOTE: EFA deficiency is rare in humans but is usually seen in infants recieving formular diets which have a low fat content. It can also be seen in patients maintained on intravenous nutrition, low in EFA for longer periods.  Details A. Simple Lipids I. Neutral Fats This is the simplest class of lipids, also called triacylglycerol. They are the esters of the alcohol glycerol and fatty acids. The acids (R-COOH) forming the ester bonds are almost the long chain monocarboxylic acids of even chain length.  If all the 3 fatty acids are the same and if R were C15H35COOH , the fat would be known as tripalmitin since it consists of 3 palmitic acid residues esterified with glycerol. In a mixed acylglycerol, more than one fatty acid is involved. In naturally occurring fats, the proportion of triacylglycerol molecules containing the same fatty acid residue in all 3 ester positions is very small. They are nearly all mixed acylglycerols. The triacylglycerols are the storage form of fatty acids and thus are the most important class of lipids metabolically.  2. WAXES If the fatty acid is esterified with a high molecular weight monohydric alcohol such as Cetyl alcohol (C16H33OH), instead of with glycerol, the resulting compound is called a wax. Waxes are not important metabolically but can be used in pharmaceutical and costmetic industries.  B. Compound or Complex Lipids The neutral fats are quantitatively the most prevalent class of lipids in most living tissues, but the compound lipids are the most biologically important Compound lipids are a group of compounds that differ considerably in chemical composition. all lipid soluble, surface active compounds. collectively called complex lipids. found in high concentrations in most biological membranes. They all contain a hydrophobic group, esterified to either glycerol or sphingosine and a hydrophyllic group, either a phosphate ester or a carbohydrate  Phospholipids The phospholipids include the following: Phosphatidic acid and phosphatidyl glycerol Phosphatidyl choline Phosphatidyl ethanolamine Phosphatidyl inositol Phosphatidyl serine Lysophospholipids Plasmalogens and Sphingomyelin  Phosphoglycerides (glycerophospholipids) The most common class of compound phospholipids is the glycerophospholipids (also called the phosphoglycerides) which are substituted diacyl- glycerophosphoric acid (phosphatidic acid). Phosphoglycerides are phosphate esters of diglycerides(diacylglycerols). Glycerol -3-phosphate is the structural backbone of the phosphoglycerides. Two fatty acids are esterified to glycerol-3-phosphate to produce the phosphatidic acid, which are intermediates in the synthesis of triacylglycerols and various other phosphoglycerides.  GLYCEROPHOSPHOLIPIDS. Glycerophospholipids are formed from phosphatidic acid (PA) and an alcohol ie the phosphate group on PA can be esterified to another compound(usually a nitogenous base) containing an alcohol group. Examples PA + Glycerol = phosphatidylglycerol PA + Choline = phosphatidylcholine (lecithin) PA + Ethanolamine = phosphatidylethanolamine (cephalin) PA + Serine =phosphatidylserine PA + Inositol = phosphatidylinositol  Phosphatidylglycerol and cardiolipin and functions When X of the phosphatidic acid moiety is replaced by glycerol, we have phosphatidyl glycerol which occurs in relatively large amounts in mitochondrial membranes and is the precursor of cardiolipin. Two molecules of PA esterifies through their phosphate groups to an additional molecule of glycerol to form diphosphatidylglycerol, also called cardiolipin.  CARDIOLIPIN (DIPHOSPHATIDYLGLYCEROL)  Cardiolipin Cardiolipin is the major lipid of the mitochondrial membrane. In eukaryotes, cardiolipin is found exclusively in the inner mitochondrial membrane where it appears to be required for the maintenance of certain respiratory chain complexes. Their reduced level or structural impairment cause mitochondrial dysfunction in a number of systemic diseases. The common serologic test for syphilis - the veneral disease research laboratory (VDRL) test, utilizes cardiolipin, as an antigen. This is because cardiolipin is antigenic and is recognised by antibodies raised against Treponema pallidum, the bacterium that causes syphilis. Phosphatidylcholine -PC  Phosphatidylcholine (Lecithin) -PC By esterifying choline or trimethylethanolamine (see below) HOCH2CH2N+(CH3)3, to the phosphoric acid portion of phosphatidic acid (X), one gets phosphatidylcholine (also called lecithin). The lecithins are widely distributed in the cells of the body, having both metabolic and structural functions. They are the most abundant phospholipid of the cell membrane and represent a large proportion of the body’s store of choline. They are the major storage form for choline inside the brain from which the neurotransmitter acetylcholine is synthesized.  Choline is also required in metabolism as a store of labile methyl groups. Lecithin (as dipalmitoyl lecithin- see below) is a very effective surface active agent(surfactant), preventing adherence, due to surface tension, of the inner surfaces of the lungs aveoli. Its absence from the lungs of premature infants cause respiratory distress syndrome (RDS). In this syndrome the lung becomes stiff, expands with difficulty and has many collapsed portions. Dipalmitoyl lecithin Phosphatidylethanolamine - PE  Phosphatidylethanolamine Phosphatidyl ethanolamine (cephalin)- (PE) differs from phosphatidylcholine (lecithin)-PC only in that ethanolamine replaces choline. PC and PE are the most abundant phospholipids in most eukaryotic cells. Phosphatidylinositol -PI  Phosphatidylinositol -PI PI is an unsual phospholipid in that it often contains stearic acid on C-1 and arachidonic acid on C-2 of the glycerol backbone. PI therefore serves as a reservoir of arachidonic acid in membranes and thus provides the substrate for prostaglandins synthesis when required. The Disphosphate derivative of inositol (phosphatidyl inositol 4,5 bisphosphate) is an important constitute of cell membrane phospholipids. It is also a precursor of second messengers. With stimulation by a suitable hormone agonist, it is split into diacylglycerol and inositol trisphosphate both of which are second messengers. Phosphatidylserine  Phosphatidylserine -PS Phosphatidyl serine is cephalin-like and contains the amino acid serine rather than ethanolamine and are found in the cell membranes and in tissues. Phosphatidyl serine also plays a role in apoptosis (programmed cell death). The highly polar serine and choline groups of the phosphoglycerides make these compounds water soluble while their fatty acyl groups confer solubility in non polar agents. Lysophospholipids  Lysophosphipids These are phosphoacylglycerols containing only one acyl radical e.g. lysolecithin (see below), important in the metabolism of phospholipids. These compounds constitutes as much as 10% of the phospholipids of brain and muscle. PLASMALOGEN  PLASMALOGEN When the fatty acid at C-1 of a glycerophospholipid is replaced by an unsaturated alkyl group attached by an ether(rather than by an ester) linkage to the core glycerol molecule, a plasmalogen is produced. E.g Phosphatidalethanolamine (abundant in nerve tissue), is the plasmalogen that is similar in structure to phophatidylethanolamine. In some instances, choline, serine or inositol may be substituted for ethanolamine. Phosphatidalcholine(abundant in heart tissue) is the other quantitatively significant ether lipid in mammals.  SPHINGOLIPIDS This is the 2nd class of complex phospholipids. The basic structural components is an N-acyl derivative of the unsaturated fatty alcohol known as sphingosine Sphingosine  Sphingosine Sphingosine is thus an amino alcohol that contains a long, unsaturated fatty alcohol hydrocarbon chain or it may be looked at as containing a long-chain monounsaturated alcohol bound to ethanolamine. In addition to sphingosine, all sphingolipids contain a fatty acid. None contains glycerol. Sphingolipids abound in the nervous system as components of myelin and other structural lipids. They occur to a lesser extent in the liver, spleen, and bone marrow.  Ceramide The simplest sphingolipids, consist of a fatty acid, bound to sphingosine. In humans, ceramides function principally as intermediates in the synthesis of other sphingolipids; all other sphingolipids thus contain ceramide. Ceramide sphingomyelin Sphingomyelin  Sphingomyelin The backbone of sphingomyelin is the amino alcohol sphingosine rather than glycerol. A long-chain fatty acid is attached to the amino group through an amide linkage, producing a ceramide (this also serve as a precusor of glycolipids). The most common fatty acids in SM are palmitic (16:0),stearic (18:0), lignoceric (24:0) and nervonic acids (24:1). The SM of myelin contains predominantly lignoceric acid and nervonic acid, whearas that of gray matter contains largely stearic acid.  The alcohol group (the primary hydroxyl group) at C-1 of sphingosine is esterified to phosphorylcholine, producing sphingomyelin. This is the only significant sphingophospholipid in humans. Sphingomyelin is an important constituent of the myelin of nerve fibres. The myelin sheath is a layered, membranous structure that insulates and protects neuronal fibres of the central nervous system. GLYCOLIPIDS  GLYCOLIPIDS Glycolipids, as their name implies are sugar containing lipids. They are also called glycosphingolipids and are compounds of fatty acid with carbohydrate, esterified to sphingosine but No phosphoric acid. In animal cells, glycolipids, like sphingomyelin, are derived from sphingosine. The amino groups of the sphingosine backbone is acylated by a fatty acid to give ceramide, as in sphingomyelin.  Glycolipids differ from sphingomyelin in the nature of the unit that is linked to the primary hydroxyl group of the sphingosine backbone. In glycolypids, one or more sugars (rather than phosphoryl choline) are attached to this group. The simplest glycolipid is cerebroside, in which there is only one sugar residue. The cerebrosides thus consists of a hexose sugar such as glucose or galactose, bound to a ceramide Glucocerebroside Structure of Ganglioside  Gangliosides More complex Glycolipids, such as gangliosides, may contain a branched chain of as many as seven sugar residues (oligosasccharide). Gangliosides are thus sialic acid containing glycosphingolipids, highly concentrated in ganglion of the central nervous system particularly in the nervous endings. Gangliosides consist of ceramide bound to an oligosaccharide that contains an acidic sugar such as N-acetylneuraminic acid (sialic acid) In summary gangliosides are more complex glycolipids that occur in the brain. They contain sialic acid (e.g. N-acetyl neuraminic acid NANA); Ceramide (containing fatty acids of which 80-90% are 18 chain length), and several molecules of hexoses (glucose, galactose, N-acetylgalactosamine)  Gangliosides are also found in the nervous tissues in high concentration. The simplest gangioisde found in tissues is GM3, which contains ceramide, one molecule of glucose, one molecule of galactose -NANA. GM1 (a more complex gangioside derived from GM2) is known to be a receptor in human intestine for cholera toxin. Other gangliosides may contain one to 5 molecules of sialic acid; hence we have mono, di, trisialogangliosides etc.  Sulfatides: These are sulphated cerebrosides or cerebroside-sulfate esters Sulfatides DERIVED LIPIDS  Steroids The steroids are often in association with fat. All of the steroids have a similar cyclic nucleus resembling phenanthrene (rings A, B, and C) to which a cyclopentane ring (D) is attached. However, the rings are not uniformly saturated, so the parent (completely saturated) substance is better designated as cyclopentanoperhydrophenanthrene. The carbon positions are numbered as indicated below  In the structural formular of steroids, a simple hexagonal ring denotes a completely saturated 6C ring (not a benzene ring). Methyl side chains are shown as single bonds, occurring typically at positions 10 and 13 (constituting C atoms 19 and 18). A side chain at position 17 is usual. If the compound has one or more hydroxyl groups and no carbonyl or carboxy groups, it is a sterol and the name terminates in –ol e.g. cholesterol.  Cholesterol Cholesterol is widely distributed in all cells of the body, but particularly in nervous tissue. It is the parent compound of all steroids synthesized in the body including the steroid hormones. It occurs in animal fats but not in plant fat. It is designated as 3-hydroxy-5, 6 cholestene Other important sterols and steroids are the bile acids, adrenocortical hormones, sex hormones, D-Vitamins, cardiac glycosides etc.  PROPERTIES OF FATTY ACIDS 1. Solubility The bulk of the fatty acid chain is hydrocarbon which has non-polar characteristics. For this reason, fatty acids are generally not very soluble in water except the short length ones such as acetic and butyric acids which exhibit acidic properties. In spite of the fact that the PKa values of fatty acids are between 4.5 – 5.0, the longer chain ones do not show acidic character because of their low solubility in water.  PROPERTIES OF FATTY ACIDS 2. Melting Point/Density Fats exist either as solids or liquids at room temperature of about 200c. Animal fats that contain saturated fatty acids are solid while plant fats that contain a good deal of unsaturated fatty acids are liquid at this temperature. The latter are referred to as oils. Generally, saturated fatty acids with chain lengths of ten and above are solids at room temperature. Increase in the degree of unsaturation of a fatty acid will lower its melting point.  The melting points of even numbered carbon fatty acids increase with chain length and decrease with points of unsaturation eg a triacylglycerol of three saturated fatty acids of 12 carbons or more is solid at body temperature while those with fatty acid residues of 18:2 is liquid even below 00c. Membrane lipids must be fluid at all environmental temperatures and are thus more unsaturated than storage lipids. The density of fats lie between 0.8 and 0.9g/cm3, meaning that they are lighter than water. 3. Micelles Due to the bulky, hydrocarbon nature of lipids, they are sparingly soluble in water. The slight solubility of polar lipids is due to its content of polar groups. At a critical concentration of such a polar lipid is water, a micelle is formed. Here the polar molecules form into particles in which the polar groups are on the surface in contact with water while the hydrocarbon chains are on the inside. If the polar lipid is in an oil-water interface, it becomes oriented in such a way that the polar group is in the water phase while the non-polar group is in the oil phase.  The formation of micelles and mixed micelles between bile salts and products of fat digestion is important in increasing absorption of lipids from the intestine. Emulsions, which are larger particles, are usually formed by non-polar lipids in an aqueous medium Micelle  PROPERTIES OF FATTY ACIDS 4. Hydrolysis Enzymes called lipases hydrolyzes tracylglycerols to give fatty acids and glycerol. Pancreatic lipase hydrolyzes the ester bonds in position 1 and 3 in preference to that in position 2 to give 2-monoacylglycerol (see metabolism of lipids later) Alkaline hydrolysis of a fat is called saponification. As shown below, the products of a saponification reaction are glycerol and the alkali salts of the components fatty acids which are called soaps. Alkaline hydrolysis of fat  PROPERTIES OF FATTY ACIDS 5. Hydrogenation/Halogenation A very important property of unsaturated fatty acids is their tendency to become hydrogenated at the double bonds in the presence of a catalyst such as Nickel. In this process, the oily lipid becomes hardened. This is the process used for converting liquid fats of mainly plant origin into solid fats and this is how margarine is made. The other important addition reaction on the double bond is halogenations as shown below Halogenation  PROPERTIES OF FATTY ACIDS 6. Oxidation and Rancidity Fatty acids with double bonds are liable to chemical oxidation by atmospheric oxygen with the formation of hydroperoxides. These decompose into keto and hydroxyl-keto acids. The accumulation of these products leads to unpleasant tastes and odours in a fat and the process that leads to this is described as oxidative rancidity. In order to avoid this, antioxidants are used to protect food products that contain a large proportion of lipids.  In brief, Rancidity is a chemical change that leaves unpleasant odour and taste in fats. The oxygen of the air attacks the double bonds in fatty acids to form a peroxide linkage. Free-radicals are produced leading to a chain reaction. Lead or copper catalyzes rancidity; while exclusion of oxygen or the addition of antioxidants delays the process.  THANK YOU FOR LISTENING