Lipids & Membranes: Structure and Function PDF

LIPIDS & MEMBRANES STRUCTURE AND FUNCTION Dr. Male Keneth 1 2  Chapter at a Glance Classification of lipids Classification of fatty acids Saturated and unsaturated fatty acids Glycerides: Triacylglycerols (TAGs)/ Neutral fats Phospholipids (...

LIPIDS & MEMBRANES STRUCTURE AND FUNCTION Dr. Male Keneth 1 2  Chapter at a Glance Classification of lipids Classification of fatty acids Saturated and unsaturated fatty acids Glycerides: Triacylglycerols (TAGs)/ Neutral fats Phospholipids (glycerophospholipids) Non-phosphorylated lipids/ sphingolipids (Sphingomyelin & Glycolipids) Eicosanoids e.g. prostaglandins, thromboxanes, leukotrienes Isoprenoids; Steroids 3  Objectives Give a general description/ definition of lipids Explain the structural and functional roles of lipids Classify lipids based on either functional or chemical basis with solid examples Give an analysis on the functions, chemical and physical properties of the different classes of lipids including their application in membranes. Note: we shall emphasize the chemical structure of the various lipids as a basis for their biological importance. 4  Definition  Biological molecules that are insoluble in aqueous solutions and soluble in organic solvents e.g., ether, benzene, acetone, chloroform  As molecules that are largely hydrocarbon in nature, lipids represent highly reduced forms of carbon upon whose oxidation in metabolism, yield large amounts of energy.  Lipids are thus the molecules of choice for metabolic energy storage (9.45 kcal/g)  Proteins/Carbohydrates yield (about 4 Kcal/g) 5  Functions of lipids They provide storage form of energy (as triacylglycerols in the adipose tissue). They serve as structural components of biological membranes (phospholipids and cholesterol). Some lipids and lipid derivatives serve as vitamins and hormones. Help in absorption of fat soluble vitamins Lipophilic bile acids aid in lipid solubilization (emulsifying agents) Protect internal organs by providing a cushioning effect (pads of fat) 6  Functions of lipids, cont’d Other lipids act as metabolic regulators such as; enzyme cofactors ( e.g. coenzyme A) hydrophobic anchors (dolichols) for proteins and intracellular messengers Electron carriers (coenzyme Q, plastoquinone) Improves taste and palatability of food Enzyme cofactors Light-absorbing pigments (carotenoids) 7  Lipid Classification 1 Based on groups of two’s: Saponifiable lipids have two subclasses Simple saponifable has two sub-categories Waxes Triglycerides Complex saponifable has two subcategories Phosphoglycerides Sphingolipids Nonsaponifiable have two subclasses Steroids Prostaglandins 8 Saponification: When triglycerides in fat/oil react with aqueous NaOH or KOH, they are converted into soap and glycerol. This is called alkaline hydrolysis of esters. 9  Lipid Classification 1 cont’d Lipids Saponifiable Nonsaponifiable Simple Complex Steroids Prostaglandins Sphingolipids Phosphoglycerides Waxes Triglycerides 10 Classification 2 according to function 11  Classification 3 Four Main Groups Fatty Acids – Saturated – Unsaturated Glycerides glycerol-containing lipids Nonglyceride lipids – Sphingolipids – Steroids – Waxes Complex lipids lipoproteins 12 Classification 3 cont’d 13   Fatty acids  Are long-chain hydrocarbon molecules containing a carboxylic acid moiety, COOH at one end.  At physiological pH, the carboxyl group is readily ionized, rendering a negative charge onto the fatty acids. 14  zig-zag amphipathic kink 15  Fatty acids  Form part of a variety of other lipids, the triacylglycerols and the waxes. Fatty acids have 4 -24 C atoms although the common ones in biological systems range from 12-24. Those with 16 and 18 carbon atoms are the most abundant. Most of the fatty acids have even number of carbon atoms as they are synthesized in biological systems by condensation of two-carbon acetate units although those with an odd number do exist e.g. propanoic acid. 16  Fatty acids Physiological roles of Fatty acids: 1. As the components of more complex membrane lipids. 2. As the major components of stored fat in the form of triacylglycerols. 3. Are building blocks of phospholipids, glycolipids and cholesterol esters 4. Fatty acids derivatives act as hormones and intracellular messengers 17  Fatty acids  Fatty acid nomenclature The numbering of carbons in fatty acids begins with the carbon of the carboxylate group. C14 C16 C18 O C8 C10 C12 C2 C4 C6 C15 C17 C9 C11 C13 C3 C5 C7 C1 HO C14 C16 C18 O C8 C10 C12 C2 C4 C6 C C17 C9 C11 C13 C3 C5 C7 H15 C1 HO 18  Fatty acid nomenclature Names do not ideally describe the nature of the fatty acid. A simplified numeric nomenclature for fatty acids uses the number of carbon atoms (chain length) followed by the number of double bonds, separated by a colon e.g. 18:0 for 18-C saturated fatty acid (stearic acid) 16:1 for 16-C monounsaturated fatty acid (palmitoleic acid) 19  Fatty acid nomenclature Naming can be done using;  the Δ (delta) designation (Is the mostly used method) or  n or ω- (omega) designation In the Δ (delta) designation - The positions of any double bonds are specified by superscript numbers following Δ (delta). Eg 16:1 Δ9. 20 Fatty acid nomenclature Carbon atoms adjacent to C1, i.e. C2, C3, C4 are also known as the α, β, γ carbons respectively, and the terminal methyl carbon is known as the ω-carbon/omega C. O    C 4 3 1 O 2 fatty acid with a cis-9 double bond 21  Fatty acid nomenclature In the n or ω-designation; naming starts from the omega carbon e.g. ω3 or n3 indicates a double bond on the 3rd carbon counting from the ω-carbon. The double bonds are always spaced by 3C. Thus, in the n or ω designation, 18:3 n3 indicates bonds in the n3, n6, n9, positions. In the Δ (delta) designation it is; 18:3 Δ 9, 12, 15 C14 C16 C18 O C8 C10 C12 C2 C4 C6 C C17 C9 C11 C13 C3 C5 C7 H15 C1 HO 22 Saturated and unsaturated fatty acids Saturated fatty acids – are those that do not contain any carbon- carbon double bond, so cannot undergo further hydrogenation. Unsaturated fatty acids – those that contain C=C double bonds. C14 C16 C18 O C8 C10 C12 C2 C4 C6 C C17 C9 C11 C13 C3 C5 C7 H15 C1 HO Unsaturated Fas: monounsaturated (one site of unsaturation) or polyunsaturated fatty acids (PUFAs) -multiple sites of unsaturation. – Over half of the fatty acid residues of plants and animal lipids are unsaturated (or polyunsaturated) 23  Common saturated fatty acids No. of common name IUPAC name melting carbons point (Co) 12:0 Laurate/ic acid Dodeconoate/ic acid 44 14:0 Myristate/ic acid Tetradeconoate/ic acid 52 16:0 Palmitate/ic acid Hexadeconoate/ic acid 63 18:0 Stearate/ic acid Octadeconoate 70 20:0 Arachidate/ic acid Eicosanoate/ic acid 75 22:0 Behenate/ic acid Docosanoate/ic acid 81 24:0 Lignocerate/ic acid Tetracosanate/ic acid 84 24  Common unsaturated fatty acids melting common name IUPAC name point (Co) 16:0 Palmitate Hexadecanoate 63 16:1 9 palmitoleate cis-9-hexadecenoate -0.5 18:0 Stearate Octadecanoate 70 18:1 9 oleate cis-9- octadecenoate 13 18:2 9,12 linoleate cis-9,12- Octadecadienoate -9 18:3 9,12,15 linolenate cis-9,12,15- Octadecatrienoate -17 20:0 Arachidate Eicosanoate 75 cis- 5,8,11,14- 20:4 5,8,11,14 arachindonate -49 eicosatetraenoate cis- 20:5 5,8,11,14,17 Timnodonate 5,8,11,14eicosapentaenoate -56 25  Fatty acids Physical Properties 1. At room temperature, saturated fatty acids from 12:0 to 24:0 are solids like wax; unsaturated fatty acids of corresponding lengths are liquids like oils. 2. They are amphipathic in nature b’se of non-polar hydrophobic carbon chain and the polar (–COOH) end. The solubility depends on how the chain outweighs the –COOH effect. 3. The melting point of fatty acids is related to chain length and degree of unsaturation. Increase in chain length increases m.p; high unsaturation lowers the m.p. 26  Physical Properties of Fatty acids Saturation 18:0 18:1 18:3 70o 13o -17o Melting point The lower part shows the packing of saturated (c) and unsaturated (d) fatty acids within membranes. Unsaturation (d) maintains the fluidity of membranes 27  Physical Properties of Fatty acids The difference in melting point is because of lower compaction/ inefficient packing of the hydrocarbon chains in unsaturated FAs which have a sharp kink at every C=C double bond in cis configuration. – This leads to a reduction in van der Waals interaction that accounts for lower melting point. Similarly, the fluidity of membranes containing high proportions of lipids with unsaturated fatty acyl residues is higher than corresponding saturated fatty acyl residues. This phenomenon has significant bearing on the activity and functions of biological membranes. 28  Fatty acids  Essential and Non essential fatty acids Non-essential fatty acids - can be synthesized in the body; from products of glucose oxidation. May be saturated or unsaturated. Essential fatty acids cannot be biosynthesized by the body in many species of animals, including humans. – They include Linolenic acid (omega 3) and Linoleic acid (omega 6). Arachidonic acid is semi-essential since it is only synthesized from essential fatty acids. 29  Essential fatty acids They are necessary for health; cannot be produced within the human body. – They are polyunsaturated fatty acids (PUFAs). – Monounsaturated fatty acids (MUFAs) are synthesized by the body (not essential); but also very important. Monounsaturated fatty acids: Oleic acid (18:1) is the most abundant in the human body; Palmitoleic acid (16:1) also an abundant in human cells. – The Fas represent the majority of MUFAs present in membrane phospholipids, triglycerides, and cholesterol esters. Are important in maintaining low levels of LDL in the blood and also associated with elevated levels of HDL 30  Functions of Essential fatty acids 1. Required for phospholipid synthesis. They are present in all tissues, brain, blood, cell membrane and mitochondrial membranes. 2. Precursors for eicosanoids, i.e. prostaglandins, prostacyclins, thromboxanes and leukotrienes 3. Play a role in normal reproduction (Flax oil and fish oil are rich in Omega-3 fatty acids. Omega-3 acids - – help fertility by helping to regulate hormones in the body, increase cervical mucous, promote ovulation and overall improve the quality of the uterus by increasing the blood flow to the reproductive organs) 31  Essential fatty acids Functions cont’d 4. Anti – atherogenic (Inhibit formation of fatty deposits in the arteries); promote the fat mobilization from liver in order to prevent fatty liver 5. Reduce inflammation; help prevent chronic diseases, such as heart disease and arthritis. 6. Important for brain health and development, as well as normal growth and development. 7. There is good evidence that fish oil containing EPA and DHA (omega-3 FAs) may help treat heart disease, prevent heart attack and stroke, and slightly reduce high blood pressure. 32  Deficiencies 1. Reduced growth 2. Scaly dermatitis 3. Fatty liver 4. Reproductive failure 5. Urinary tract lesions, necrosis (the death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply) 6. Impaired stress resistance 33 34  Omega-6 PUFAs: Consumed in the diet esp. vegetable oils and consist of linoleic acid. Linoleic acid serves as a precursor for synthesis arachidonic acid, a component of membrane phospholipids at C-2. Also very important (thru arachidonic acid) in synthesis of Eicosanoids e.g prostaglandins. 35  Physiologically Relevant Fatty Acids Numerical Common Name and Structure Comments Symbol 14:0 Myristic acid Often found attached to the N-term. of plasma membrane-associated cytoplasmic proteins Palmitic acid 16:0 End product of mammalian fatty acid synthesis common constituent of the glycerides of human adipose tissue, Palmitoleic acid 16:1Δ9 present in all tissues but, in general, found in higher concentrations in the liver 36  Physiologically Relevant Fatty Acids, cont’d Numerical Symbol Common Name and Structure Comments 18:0 Stearic acid in animal fat Oleic acid An omega-9 18:1Δ9 monounsaturated fatty acid 18:2Δ9,12 Linoleic acid Essential fatty acid An omega-6 polyunsaturated fatty acid 18:3Δ9,12,15 α-Linolenic acid (ALA) Essential fatty acid An omega-3 polyunsaturated fatty acid 37  Physiologically Relevant Fatty Acids, cont’d Numerical Common Name and Structure Comments Symbol 20:4Δ5,8,11,14 Arachidonic acid An omega-6 polyunsaturated fatty acid. Precursor for eicosanoid synthesis 20:5Δ5,8,11,14,17 Eicosapentaenoic acid (EPA) An omega-3 polyunsaturated fatty acid enriched in fish oils 22:6Δ4,7,10,13,16,19 Docosahexaenoic acid (DHA) An omega-3 polyunsaturated fatty acid enriched in fish oils 38 39  Omega-3 Omega-6 40  Naturally occurring fatty acids Most naturally occurring fatty acids are saturated. Double bonds are located in specific positions. There is a common pattern in the location of double bonds: monounsaturated FA: Δ9,Δ12,Δ 15 ……… Polyunsaturated FA: double bonds are never conjugated and are in the cis configuration (-CH=CH-CH2-CH=CH-)n 41  Eicosanoids Are fatty acid derivatives with a variety of extremely potent hormone like actions on various tissues Derived from arachidonic acid 3 classes: prostaglandins, thromboxanes and leukotrienes Prostaglandins: – PGE (ether-soluble); PGF (phosphate buffer soluble): modulate blood clotting, inflammatory response, muscle contraction & relaxation 42  Eicosanoids Thromboxanes: – Produced by platelets (thrombocytes) and act in the formation of blood clots. Leukotrienes – They are able to lure white blood cells to the site of injury and bind them to the vessel wall. But, overproduction of leukotrienes cause asthmatic attacks – Involved in chemotaxis, inflammation, and allergic rxns. 43  Glycerides Esters of glycerol and a variable number and type(s) of fatty acids and/or a Phosphate group. Neutral Glycerides (fats) are composed of only glycerol and a number of fatty acids. – Can have 1 to 3 fatty acids, each of which may be different. 44 – Depending on the number of fatty acids they are called: Monoacylglycerols (MAGs) (Monoglycerides) – Glycerol + 1 fatty acid Diacylglycerols (DAGs) Diglygerides – Glycerol + 2 Fatty acids Triacylglycerols (TAGs)/Triglygerides – Glycerol + 3 fatty acids Phosphoglycerides have 1 or more phosphate group(s) 45   Triacylglycerols (TAGs) Are the simplest of lipids Neutral glycerides (fats) Simple triacylglycerols - Those containing the same kind of fatty acid in all three positions on glycerol. Mixed triacylglycerides - when different fatty acids are esterified to the hydroxyl gps of glycerol. Majority of the naturally occurring fats and oils are mixed triacylglycerides 46 TAGs Phosphoglycerides have 1 or more phosphate group(s) 47  TAGs Physical Properties Triacylglycerols Triacylglycerols are non-polar, hydrophobic and essentially insoluble in water (polar hydroxyls and the carboxyl are bound in ester linkage). Have densities lower than that of water, do not mix with water and so forms a separate phase and float on water. Vertebrate animals have specialized cells called adipocytes (fat cells) that store large amounts of triacylglycerols as fat droplets, which nearly fill the cell. – In most cells, TAGs form fat droplets in the cytosol serving as deposits of metabolic fuel. 48 49 Nomenclature & properties of neutral Glycerides Based on name(s) of the constituent fatty acids: E.g. Tristearin is a simple TAG with 3 Stearic acid residues Oleodistearin is a mixed TAG with 1 oleic and 2 stearic acid residues TAGs are the most abundant in nature but MAGs and DAGs can also be found in small amounts as important metabolites TAGs can undergo autooxidation when exposed to air Complete oxidation Yield 9Kcal/g as compared to 4Kcal/g from Proteins and CHOs due to their highly reduced and anhydrous state 50  Nomenclature & properties of neutral Glycerides Very non polar and weakly ionic unlike proteins and CHOs which are more polar and highly hydrated. 1g of TAG can store 6 times as much energy as 1g of glycogen TAGs are synthesized and stored in adipocytes (Fat cells) as fat droplets and can be mobilized into fuels molecules and transported to other tissues by blood 51  Physical & Chemical Properties Neutral Fats Insoluble in water but soluble in non – polar solvents: – Dominated by the hydrophobic alkyl groups: Weak amphiphiles The richer the fat is in short chain and unsaturated FA residues the greater the solubility and the lower the melting points – Saturation and increasing the chain length leads to elevation of m.p – E.g 52  Physical & Chemical Properties Neutral Fats Most samples of animal fats predominantly contain esters of Palmitic, stearic, Palmitoleic and linoleic acids in various proportions – Fats from diverse portions of the same organism may differ widely in composition E.g. human subcutaneous fat has more sat. FAs than liver which is richer in Unsat. Fas. Many vegetable oils and fats which exhibit diversity in FA composition are liquids at R.T 53  Chemical properties of TAGs Hydrolysis by; boiling water/steam, Acidic Basic (KOH or NaOH) – saponification to yield soaps, enzyme (Esterases/lipases): Note: The reaction is irreversible 54  Chemical properties of TAGS Hydrogenation. Vegetable oils have more unsaturated fats which make them liquid. As the degree of hydrogenation increases saturation and they become more solid. Industrial hydrogenation turns oils into fats. The hydrogenation of vegetable oils is commercially used for production of margarines. 55  Chemical Properties (cont’d) Rancidity of Fats Refers to the occurrence of an unpleasant smell and taste for fats and oil Oxidative Rancidity – Usually caused by various oxidative processes E.g; oxidation at the double bonds of unsaturated fatty acyl residues may form peroxides, which then decompose to form aldehydes of bad odor and taste (aldehydes can be poisonous). – This process is greatly increased by exposure to light. – PUFAs are readily oxidized by exposure to air. – Also due to hydrolytic enzymes naturally occurring in fats and oils Vegetable oils high in PUFAs are preserved by addition of antioxidants 56  Microbial rancidity whereby microorganisms, such as bacteria or molds (fungi), use their enzymes lipases to break down fat.  This pathway can be prevented by sterilization. Hydrolytic Rancidity due to hydrolytic enzymes that naturally occurring in fats and oils – Vegetable oils high in PUFAs are preserved by addition of ANTIOXIDANTS (Natural or Synthetic) – Natural antioxidants include polyphenols (for instance flavonoids), ascorbic acid (vitamin C) and tocopherols (vitamin E). 57  Characterization of fats. Acid number. – the no. of milligrams of KOH required to neutralize the free fatty acids in 1 g of the oil or fat. Saponification number – the no. of milligrams of KOH required tо completely saponify l00 g of the oil or fat. Iodine number. the no. of grams of iodine that combine with 100 g of oil or fat. It is а measure of the degree of unsaturation of а fat or oil; а high iodine number indicates а high degree of unsaturation of the fatty acids of the fat. Acetyl Number. The number of free hydroxyl groups in a fat or oil. The acetyl value is determined by the milligrams of KOH required to neutralize the acetic acid produced when 1 gram of fat or oil is acetylated with acetic anhydride. 58   Waxes Esters of long chain fatty acids (C14-36) with long chain alcohols (C16-30) Highly insoluble and have water-repellent properties They nurture the skin and fur of animals - wax-coated They can be used for energy storage in some organisms (Plankton) Leaves of many plants – prevent excessive evaporation of water protection against parasites. Birds have wax secreting glands to prevent their feather from being wet. 59   Waxes Skin glands of certain vertebrates secrete waxes to protect their hair and skin and keep them lubricated and waterproof. – Waxes of biological origin are commercially important too. They are widely used in pharmaceutical industries to make cosmetics, ointments and polishes, etc. High melting points (60-100C) than TAGs Bees wax is a tough wax formed from a mixture of several cpds. 60  major component of beeswax Triacontanoylpalmitate 61   Structural Lipids (Membrane lipids) These include; Phospholipids and Sphingolipids/ glycolipid 1. Phospholipids - glycerophospholipids * sphingomyelin (Phosphosphingolipids) 2. Sphingolipids – Glycolipid / Glycosphingolipids  Note: * Sphingomyelin can be categorized under Phospholipids or Sphingolipids since its backbone is Sphingosine 62 Structure  Phospholipids Generally, lipids with phosphate group Glycerol + 2 fatty acids + phosphate group  Function Structural Components of Biological Membranes – Component of cell membranes (40% in RBCs and 95% in inner mitochondrial membrane) Phospholipids play a role in Intracellular Signaling Regulation of cell metabolism Phospholipids are involved in Membrane Fusion and Exocytosis Lipid transport as part of lipoproteins  Food sources: Egg yolks, liver, soybeans, peanuts 63  Phospholipids cont’d Classes of phospholipids (i) glycerophospholipids – glycerol backbone (ii) sphingomyelin – spingosine backbone i) Glycerophospholipids/Phosphoglycerides essential for membrane structure most abundant membrane lipids no genetic defects in humans 64   Glycerophospholipids Characteristics  Are the most polar lipids, and are amphipathic – posses both hydrophillic and hydrophobic groups  They are amphoteric bearing both –vely and +vely charged groups  Complete hydrolysis yields ……….??? 65 L-Glycerol-3-phosphate and D-glycerol 1-phosphate, the backbone of phospholipids D-glycerol 1-phosphate L-Glycerol-3-phosphate (appear in small quantities) L-Glycerol-3-phosphate is the major natural phosphate ester of glycerol 66  Glycerophospholipids cont’d Are triesters of glycerol-3-phosphate; two with fatty acids and the third with phosphate group linked (phosphodiester bond) to another variable compound, X. 67  Glycerophospholipids Diacylglycerol 3 phosphate or phosphatidate (Phosphatidate) Phosphatidate is a key intermediate in the biosynthesis of other phosphoglycerides. The simplest glycerophospholipid is phosphatidic acid, which has a hydrogen atom as the variable group - X. The phosphoryl group can attach to different alcoholic groups in the biosynthesis of other phosphoglycerides 68  Glycerophospholipids cont’d Classification Glycerophospholipids include the following compounds; 1. Phosphatidylserine 2. Phosphatidylethanolamine (PE) (a cephalin) 3. Phosphatidylcholine (PC) (also called the lecithin) 4. Phosphatidylglycerol (PG) 5. Phosphatidylinositol (PI) 6. Cardiolipin (CP) 69  Common alcoholic moieties (X) 1. Serine 2. Ethanolamine 3. Choline 4. Glycerol 5. Inositol 6. phosphatidyl-glycerol 70  Saturated FA Unsaturated FA phosphatidic acid H Phosphatidylethanolamine ethanolamine Phosphatidylcholine choline Phosphatidylserine serine Phosphatidylglycerol glycerol Phosphatidylinositol inositol 4,5- 4,5-bisphosphate bisphosphate Cardiolipin phosphatidyl- glycerol 71 Cardiolipin (CL) Cardiolipin (CL) is the major lipid of mitochondrial membrane cardiolipin is found almost exclusively in the inner mitochondrial membrane where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism – the heart of mitochondrial metabolism Decreased levels lead to mitochondrial dysfunction and heart failure Cardiolipin was first found in animal hearts. 72  Phosphatidyl Inositol (PI) Often contain Stearic acid (R1) on C1 and Arachidonic acid (R2) on C2. Serves as reservoir for arachidonic acid 73  Glycerophospholipids cont’d Phospholipases The membrane phospholipids of most cells are continuously degraded and replaced. The hydrolytic enzymes responsible for degradation of membrane phospholipids are called phospholipases Types of phospholipases (are bond specific) Phospholipases A1 from the brain catalyses hydrolysis of the 1st acyl ester bond; Phospholipases A2 from the pancreas catalyses hydrolysis of the 2nd acyl ester bond while the phospholipase C and D hydrolyze the phosphodiester bonds (are also called phosphodiesterases) 74  Sites of action of phospholipases 75 Phospholipids and sphingolipids are degraded in lysosomes 76   Ether linked phospholipids Some other glycerophospholipids have one of the two fatty acids attached to glycerol in ether, rather than, ester linkage. 1. Plasmalogens  found in central nervous system and in heart muscle ether linkage at glycerol C-1  have choline and ethanolamine head groups  resistant to phospholipases 77 2. Platelet activating factor  active at very low concentration (0.1 nM)  released from leukocytes called basophils  cause platelet aggregation and vasoconstriction (via release of serotonin from platelets)  involved in smooth muscle contraction – inflammation, allergic response  acetyl group makes it water soluble 78   Sphingolipids Structure and Functions Outline 79  Sphingolipids Backbone (Base structure) – Sphingosine Sphingosine - an 18-carbon amino alcohol Ceramides are amide linkages of fatty acids to the nitrogen of sphingosine Sphingomyelins are phosphocholine or phosphoethanolamine derivatives of Ceramides – therefore can be called Phospholipids Glycosphingolipids ( glycolipids) are ceramides with one or more sugars in beta-glycosidic linkage at the 1-hydroxyl group Glycosphingolipids with one sugar are cerebrosides Gangliosides - ceramides with 3 or more sugars, one of which is a Sialic acid (NANA) 80   Sphingolipids Sphingolipids (not all are phospholipids) sphingomyelin, neutral glycolipid and gangliosides Note that Sphingolipids Are abundant in tissues of CNS Are involved in recognition events at the cell surface, such as cell recognition & cell-cell communication Ceramide (sphingosine + FA) is the structural unit common to all sphingolipids 81  Sphingolipids Sphingosine Sphingosine is an 18-carbon amino alcohol Is the backbone of all Sphingolipids Is a lipid/ amino alcohol with a long hydrocarbon tail and a polar domain that includes an amino group H H 82  Sphingolipids Ceramide sphingosine Ceramide makes the core structure of naturally occurring phospholipids including glycosphingolipids 83   Sphingomyelins Ceramide + Phosphocholine (i.e. ceramide derivative) – The only phospholipids in membranes not derived from Glycerol – The Only sphingolipid that contains phosphate – The Only sphingolipid that has no sugar moiety. – Conformation resembles that of Phosphatidyl Choline – Found abundantly in brain and nerve tissues – Surround and insulate the nerve cell axons – Degraded by Sphingomyelinase which removes the Phosphoryl choline unit. – The resultant Ceramide is cleaved by ceramidase to give sphingosine and a free FA 84 Sphingomyelins X = phosphocholine 85   Glycolipids Lipids containing a sphingosine, fatty acid and a carbohydrate They are located in the outer leaflet of the plasma membrane, where they interact with the extracellular environment. i. As such, they play a role in the regulation of cellular interactions, growth, and development. ii. Glycolipids are antigenic - source of blood group antigens, [Note: The carbohydrate portion of a glycolipid is the antigenic determinant.] iii. also serve as cell surface receptors for cholera and … tetanus toxins, as well as for certain viruses and … microbes. 86 Sphingolipids at Cell Surface are Sites of Biological Recognition The carbohydrate moieties define the human blood groups. 87  Classes of Glycolipids There are three major classes: 1. Cerebrosides (Neutral glycosphingolipids) – (Ceramide + contain 1 sugar moiety) 2. Globosides (Ceramide + 2 or more sugars) (ceramide oligosaccharides). 3. Gangliosides (Like Globoside + 1 Sialic acid (NANA) Globoside + sialic acid = Ganglioside Most complex Sphingolipids Are acidic at physiological pH 88 89 90 91 92 93 94 95 96  Terpenes Unsaturated compounds formed by joining isoprene units One isoprene unit contains five carbon atoms 2 - methylbuta – 1,3 – diene are components of a wide variety of fruit and floral flavours and aromas. in plants they can be oxidized to produce terpenoids responsible for the distinctive aroma of spices. 97  Isoprene units can be linked head to tail to form linear terpenes or in rings to form cyclic terpenes. Limonene is a cyclic terpene found in citrus fruits. It is made of two isoprene units linked in a ring. 98  β-carotene is a linear terpene found in carrots. It is made from 8 isoprene units linked head to tail. Menthol is a cyclic terpenoid – a terpene which has been oxidised. It is found in peppermint and has a distinctive aroma. 99 The Isoprene Rule 100 101  Squalene, a triterpene, is a precursor of steroid molecules a natural 30-carbon organic compound originally obtained for commercial purposes primarily from shark liver oil 102 Lycopene and -carotene are tetraterpenes called carotenoids a bright red carotene and carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, watermelons, gac, and papayas, an organic, strongly colored red-orange pigment abundant in plants and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons. 103 Conversion to Vitamin A -carotene OH OH retinol retinol 104   Steroids Based on a core structure consisting of three 6-membered rings A, B, C & one 5-membered ring D, all fused together. It is called a steroid nucleus 105  Cholesterol  Steroids: (i) cholesterol and sterols of plants and fungi (ii) steroid hormones (iii) bile salts  Roles of cholesterol in mammals (i) structural component of plasma membrane and modulates membrane fluidity (ii) precursor of steroid hormones and bile acids  cholesterol is rarely found in plants, never in bacteria 106  Cholesterol Cholesterol is the major steroid in human body. It is precursor for all other steroids in animals Steroid hormones serve many functions in animals - including salt balance, metabolic function and reproductive function Steroids are amphipathic with polar –OH group and Hydrophobic tail 107  Cholesterol Functions – Component of cell membranes – Precursor to other substances Sterol hormones Vitamin D Bile acids/salts Synthesis – Made mainly in the liver Food sources – Found only in animal foods 108  Cholesterol Most abundant sterol in animal tissue particularly in the nervous tissue Major constituent of cell membrane and plasma lipoproteins Precursor of a large no. of equally important steroids:- Bile acids, adrenocortical hormones e.g cortisol, sex hormones and D - Vitamins When it is mixed with fat or oil, it enables the latter to absorb large amounts of water by forming water-in-oil emulsions 2/3 of cholesterol is found in combination with mostly unsaturated fatty acids as cholesteryl esters 109 Cholesterol 110  Steroid hormones Sex hormones 1. Estradiol - Secreted by 2.Testosterone - It is the ovaries, it is a primary principal male sex hormone female sex hormone secreted primarily by the testes & the ovaries 3. Progesterone/ progestins (pregnancy hormones) 111 112   Ergosterol is provitamin form 4.Adrenocortical Hormones of vitamin D2; Aldosterone UV light, rt Cortisol Vitamin D2 ( Ergocalciferol) Vitamin D is a steroid and a derivative of cholesterol, e.g cholecalcipherol, that is known as the vitamin D3.  Bile salts/Bile acids Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. They act as emulsifying agents in the intestine Different molecular forms of bile acids can be synthesized in the liver by different species. Bile acids are conjugated with taurine or glycine in the liver, forming bile salts. 114  Membranes Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media Lipid micelle Lipid bilayer Lipid vesicle (or liposome) (ionized fatty acids) (membrane lipids) < 20 nm in diameter Extensive, up to 106 nm Hydrocarbon tails pack with mainly van der Waals attractive forces Polar groups interact with water with electrostatic and H-bonding forces. 115 Cell membranes are phospholipid bilayers 116  Cholesterol can pack with phospholipids in a 1:1 ratio 117  The “Fluidity” of a Lipid Bilayer Is Determined by Its Composition Short chain fatty acyl groups tend to increase lateral mobility Unsaturated fatty acids tend to increase fluidity Cholesterol and other sterols tend to impede fatty acid mobility (act as a fluidity buffer) 118  Lipids as signals, cofactors, and pigments  Phosphatidylinositols act as intracellular signals  Eicosanoids carry messages to nearby cells  Steroid hormones carry messages between tissues  Vitamins A and D are hormone precursors 119  WISH YOU THE VERY BEST 120