Lipids I 2024 PDF

Biochemistry I Dr. Shumaila Usman Associate Professor College of Molecular Medicine Lipids & Storage lipids (Biochemistry) Lipids Lipids is insoluble in polar solvent and have good solubility in non-polar solvent Lipids has hydrocarbon chain and ester gro...

Biochemistry I Dr. Shumaila Usman Associate Professor College of Molecular Medicine Lipids & Storage lipids (Biochemistry) Lipids Lipids is insoluble in polar solvent and have good solubility in non-polar solvent Lipids has hydrocarbon chain and ester group Lipids classified as simple and complex lipids Lipid composed by ester of fatty acid … The main function of lipids : Energy storage Structural components of cell membranes As important signalling molecules Oxidation of lipids are produced more energy than the oxidation of carbohydrates Humans have fat tissue under the skin, in the abdominal cavity, and in the mammary gland Fatty Acids Are Hydrocarbon Derivatives Carboxylic acids with hydrocarbon chains containing between 4 to 36 carbons Almost all natural fatty acids have an even number of carbons. Most natural fatty acids are unbranched. Saturated: no double bonds between carbons in the chain Monounsaturated: one double bond between carbons in the alkyl chain Polyunsaturated: more than one double bond in the alkyl chain  Fatty Acid Nomenclature Simplified format for unbranched fatty acids: chain length and number of double bonds separated by a colon. (e.g., 16:0, 18:1). Example: Palmitic acid (16 carbons, saturated) is abbreviated as 16:0. Example: Oleic acid (18 carbons, one double bond) is abbreviated as 18:1. Structural Representation: Each line segment in the zigzag represents a single bond between adjacent carbons. Carboxyl carbon assigned as C-1, and the α carbon next to it as C-2. Position of double bonds specified relative to C-1 (Δ, delta), with a superscript number. Examples of Nomenclature: Oleic acid with a double bond between C-9 and C-10 is designated as 18:1(Δ9). A 20-carbon fatty acid with double bonds between C-9 and C-10, and C-12 and C-13 is designated as 20:2(Δ9,12). Common Characteristics: Most occurring fatty acids have even numbers of carbon atoms (12 to 24) in an unbranched chain. Even number of carbons results from the synthesis involving successive condensations of two-carbon acetyl units. Double Bond Patterns: Common pattern in monounsaturated fatty acids: double bond between C-9 and C-10 (Δ9). Polyunsaturated fatty acids: Double bonds generally at Δ12 and Δ15 (except arachidonic acid). Configuration and Exceptions: Double bonds are generally in cis configuration in naturally occurring unsaturated fatty acids. Exceptions: Trans fatty acids produced by fermentation in the rumen of dairy animals.  Importance of polyunsaturated fatty acids (PUFAs) with a double bond between the third and fourth carbon from the methyl end. Alternative nomenclature based on the ω (omega) carbon is used to emphasize the physiological significance of the first double bond. ω (Omega) Carbon: ω carbon is the carbon most distant from the carboxyl group, labeled as C-1. Double bond positions are indicated relative to the ω carbon. Classification: PUFAs with a double bond between C-3 and C-4 are omega-3 (ω-3) fatty acids. Those with a double bond between C-6 and C-7 are omega-6 (ω-6) fatty acids. Example: Eicosapentaenoic Acid (EPA): Standard nomenclature: 20:5(Δ5,8,11,14,17). Alternative: Designated as an omega-3 fatty acid, highlighting the biologically important double bond in the omega-3 position.  Melting points influenced by chain length and degree of unsaturation. Saturated fatty acids (12:0 to 24:0) at 25°C: waxy consistency. Unsaturated fatty acids (same lengths): oily liquids. Melting point difference due to varying packing of fatty acid molecules. Fully saturated compounds: Free rotation, flexible, fully extended form, tight packing in crystalline arrays. Unsaturated fatty acids: Cis double bonds introduce kinks, hinder tight packing, weaker interactions. Structural influence on melting points: Fully saturated - tight packing, unsaturated - hindered packing. Consequence of weaker interactions: Poorly ordered arrays of unsaturated fatty acids, lower melting points.  Triacylglycerols Are Fatty Acid Esters of Glycerol Simplest lipids constructed from fatty acids are triacylglycerols, also known as triglycerides, fats, or neutral fats. Triacylglycerols consist of three fatty acids, each esterified to a glycerol molecule. Simple triacylglycerols have the same fatty acid in all three positions; examples include tripalmitin (16:0), tristearin (18:0), and triolein (18:1). Most naturally occurring triacylglycerols are mixed, containing two or three different fatty acids. Triacylglycerols are nonpolar and hydrophobic due to ester linkages between polar hydroxyls of glycerol and polar carboxylates of fatty acids. Their nonpolar nature makes triacylglycerols essentially insoluble in water. Lipids, including triacylglycerols, have lower specific gravities than Triacylglycerols Provide Stored Energy and Insulation Triacylglycerols form microscopic, oily droplets in the cytosol of most eukaryotic cells, serving as fuel depots. Adipocytes, specialized cells in vertebrates, store large triacylglycerol amounts as fat droplets that fill the cell. Plant seeds store triacylglycerols as oils, providing energy and biosynthetic precursors during germination. Adipocytes and germinating seeds house lipases, enzymes catalyzing triacylglycerol hydrolysis. Lipases release fatty acids from stored triacylglycerols, exporting them for use as fuel  Reasons Why is Partial Hydrogenation Applied to Cooking Oils? Partial hydrogenation is utilized in cooking oils, such as vegetable oils, to enhance their stability and shelf life. During this process, hydrogen is added to the oil, leading to the saturation of some double bonds in the fatty acids. This saturation results in a more solid consistency at room temperature, making the oil more suitable for various culinary applications. The altered chemical structure achieved through partial hydrogenation increases the stability of the oil, reducing the likelihood of rancidity and ensuring a longer usability period for cooking purposes. Why Are Vegetable Oils Liquid at Room Temperature? Vegetable oils, such as corn (maize) oil and olive oil, are primarily composed of triacylglycerols with unsaturated fatty acids, making them liquids at room temperature. The presence of unsaturated fatty acids introduces kinks in the fatty acid chains, preventing close packing and  What Are the Implications of Partial Hydrogenation on Cooking Oils and Human Health? Purpose of Partial Hydrogenation: Partial hydrogenation is employed to enhance the stability of cooking oils, especially vegetable oils, by converting liquid unsaturated fats into more stable saturated or partially saturated fats. Composition and States of Natural Fats: Natural fats, found in vegetable oils, dairy products, and animal fat, are complex mixtures containing various fatty acids. Vegetable oils, rich in unsaturated fatty acids, remain liquids at room temperature, while those containing saturated fatty acids, like tristearin in beef fat, are solid. Health Implications: Partial hydrogenation, while enhancing stability, leads to the creation of trans fats and saturated fats, associated with harmful health effects, such as increased risk of cardiovascular diseases.  What Are the Consequences of Prolonged Exposure of Lipid-Rich Foods to Oxygen, and How Does Partial Hydrogenation Address These Issues? Rancidity Due to Oxidative Cleavage: Lipid-rich foods exposed to oxygen can undergo oxidative cleavage of double bonds in unsaturated fatty acids, resulting in the formation of aldehydes and carboxylic acids. This process leads to rancidity, characterized by an unpleasant taste and smell. Partial Hydrogenation Purpose: Partial hydrogenation of commercial vegetable oils was historically employed to enhance shelf life and improve stability, particularly at high temperatures used in deep- frying. This process involves converting some cis double bonds to single bonds and raising the melting temperature of oils, making them more solid at room temperature. Undesirable Effect of Partial Hydrogenation: While addressing stability concerns, partial hydrogenation also introduces an undesirable effect: the conversion of some cis double bonds to trans double bonds.  Solubility and Melting Point of Fatty Acids Solubility decreases as the chain length increases Melting Point decreases as the chain length decreases decreases as the number of double bonds increases Waxes Serve as Energy Stores and Water Repellents Biological waxes are esters of long-chain (C14 to C36) saturated and unsaturated fatty acids with long-chain (C16 to C30) alcohols. Their melting points (60 to 100 °C) are generally higher than those of triacylglycerols. In plankton, the free-floating microorganisms at the bottom of the food chain for marine animals, waxes are the chief storage form of metabolic fuel. Structural Lipids in Membranes Biological Membranes biological membranes = double layer of lipids that acts as a barrier to polar molecules and ions membrane lipids: amphipathic = one end of the molecule is hydrophobic, the other hydrophilic hydrophobic regions associate with each other hydrophilic regions associate with water Some Common Types of Storage and Membrane Lipids  Four General Types of Membrane Lipids phospholipids = have hydrophobic regions composed of two fatty acids joined to glycerol or sphingosine glycolipids = contain a simple sugar or a complex oligosaccharide at the polar ends archaeal tetraether lipids = have two very long alkyl chains ether-linked to glycerol at both ends sterols = compounds characterized by a rigid system of four fused hydrocarbon rings Ceramides Are The Structural Parent of All Sphingolipids C-1, C-2, and C-3 of sphingosine are structurally analogous of the three carbons of glycerol in glycerophospholipids ceramide = compound resulting when a fatty acid is attached in amide linkage to the –NH2 on C-2 – structurally similar to a diacylglycerol  Structural Lipids in Membranes (Polar) Contain polar head groups and nonpolar tails (usually attached fatty acids)  Diversification can come from: modifying a different backbone changing the fatty acids modifying the head groups The properties of head groups determine the surface properties of membranes. Different organisms have different membrane lipid head group compositions. Different tissues have different membrane lipid head group Glycerophospholipids Primary constituents of cell membranes Two fatty acids form ester linkages with the first and second hydroxyl groups of L-glycerol-3-phosphate. The phosphate group is charged at physiological pH. Glycerophospholipids Are Derivatives of Phosphatidic Acid glycerophospholipids (phosphoglycerides) = membrane lipids in which two fatty acids are attached in ester linkage to the first and second carbons of glycerol, and a highly polar or charged group is attached through a phosphodiester linkage to the third carbon Glycerophospholipids Are Named as Derivatives of Phosphatidic Acid Membrane lipids known as glycerophospholipids. Composed of glycerol, two fatty acids (attached in ester linkage to the first and second carbons of glycerol), and a polar or charged group (attached through a phosphodiester linkage to the third carbon). Glycerol, initially prochiral, becomes chiral upon phosphate attachment, allowing multiple naming conventions (L-glycerol 3- phosphate, D-glycerol 1-phosphate, or sn-glycerol 3-phosphate). Named as derivatives of the parent compound, phosphatidic acid, based on the polar alcohol in the head group. Glycerophospholipids Are Named as Derivatives of Phosphatidic Acid Examples of polar head groups include choline and ethanolamine in phosphatidylcholine and phosphatidylethanolamine, respectively. Cardiolipin is a two-tailed glycerophospholipid where two phosphatidic acid moieties share the same glycerol as their head group. Cardiolipin is prevalent in bacterial membranes, while in eukaryotic cells, it is primarily found in the inner mitochondrial membrane, supporting the endosymbiosis hypothesis for the origin of mitochondria.  Glycerophospholipids share a common structural feature: the head group attachment to glycerol through a phosphodiester bond. The phosphate group in the phosphodiester bond carries a negative charge under neutral pH conditions. The polar alcohol in the head group can exhibit various charge states: o Negatively charged (e.g., phosphatidylinositol 4,5-bisphosphate). o Neutral (e.g., phosphatidylserine). o Positively charged (e.g., phosphatidylcholine, phosphatidylethanolamine). These varying charges have significant implications for the surface properties of membranes, influencing their overall behavior and functions. Glycerophospholipids Are Named as Derivatives of Phosphatidic Acid A phosphodiester bond joins the head group to glycerol The phosphate group can bear a negative, neutral, or positive charge Phosphatidylcholine Phosphatidylcholine is the major component of most eukaryotic cell membranes. Many prokaryotes, including E. coli, cannot synthesize this lipid; their membranes do not contain phosphatidylcholine.  Some Glycerophospholipids Have Ether-Linked Fatty Acids ether lipids = one of the two acyl chains is attached to glycerol in ether, rather than ester, linkage – chain may be saturated – chain may contain a double bond between C-1 and C-2 as in plasmalogens Ether Lipids: Platelets- Activating Factor Aliphatic ether analog of phosphatidylcholine Acetic acid has esterified position C2 First signaling lipid to be identified Stimulates aggregation of blood platelets Plays role in mediation of inflammation Platelet-Activating Factor platelet-activating factor = an ether lipid that serves as a potent molecular signal – releases from leukocytes called basophils – stimulates platelet aggregation and serotonin release – plays a role in inflammation and the allergic response Sphingolipids The backbone of sphingolipids is NOT glycerol. The backbone of sphingolipids is a long-chain amino alcohol sphingosine. A fatty acid is joined to sphingosine via an amide linkage, rather than an ester linkage as usually seen in lipids. A polar head group is connected to sphingosine by a glycosidic or phosphodiester linkage. The sugar-containing glycosphingolipids are found largely in the outer face of plasma membranes. Galactolipids of Plants and Ether-Linked Lipids of Archaea Are Environmental Adaptations galactolipids = member of the glycolipids group that predominate in plant cells – one or two galactose residues are connected by a glycosidic linkage to C-3 of a 1,2-diacylglycerol Sphingolipids Sphingomyelin Ceramide (sphingosine + amide-linked fatty acid) + phosphocholine attached to the alcohol Sphingomyelin is abundant in myelin sheath that surrounds some nerve cells in animals. Sphingomyelin Is Structurally Similar to Phosphatidylcholine Sphingolipids Are Derivatives of Sphingosine sphingolipids = large class of membrane phospholipids and glycolipids – have a polar head group and two nonpolar tails – contain no glycerol – contain one molecule of the long-chain amino alcohol sphingosine or one of its derivatives Sphingomyelins sphingomyelins = subclass of sphingolipids that contains phosphocholine or phosphoethanolamine as their polar head group Cerebrosides and Globosides cerebrosides = have a single sugar linked to ceramide – those with galactose are found in the plasma membranes of cells in neural tissue – those with glucose are found in the plasma membranes of cells in nonneural tissues globosides = glycosphingolipids with 2+ sugars, usually D- glucose, D-galactose, or N- acetyl-D-galactosamine sometimes called neutral glycolipids, as they have no charge at pH 7 Gangliosides gangliosides = have oligosaccharides as their polar head groups and 1+ residues of N-acetylneuraminic acid (Neu5Ac), a sialic acid, at the termini – 1 sialic acid residue = GM (M for mono-) series – 2 sialic acid residues = GD (D for di-) series – 3 sialic acid residues = GT (T for tri-) series (and so on) Tay-Sachs disease is the result of a genetic defect in the metabolism of: A) gangliosides. B) phosphatidyl ethanolamine. C) sterols. D) triacylglycerols. E) vitamin D  Clicker questions Which sphingolipids have a single monosaccharide as a component? a.cerebrosides b.gangliosides c. globosides d.Plasmalogens cerebrosides Cerebrosides have a single sugar linked to ceramide  Glycosphingolipids and Blood Groups The blood groups are determined in part by the type of sugars located on the head groups in glycosphingolipids. The structure of sugar is determined by an expression of specific glycosyltransferases. – Individuals with no active glycosyltransferase will have the O antigen. – Individuals with a glycosyltransferase that transfers an N-acetylgalactosamine group have A blood group. – Individuals with a glycosyltransferase that transfers a galactose group have B blood group.  Sphingolipids at Cell Surfaces Are Sites of Biological Recognition prominent in the plasma membranes of neurons human blood groups (O, A, B) are determined in part by the oligosaccharide head groups of these glycosphingolipids Glycosphingolipids Determine Blood Groups  Structural and Signaling Lipids Are Degraded in the Lysosome Most cells continually degrade and replace their membrane lipids. Phospholipids are degraded by phospholipases A−D. Each phospholipase cleaves a specific bond. Gangliosides are degraded via a series of enzymatic cleavages. Failure to correctly degrade gangliosides results in build-up of lipids in  Lipid Anchors Some membrane proteins are lipoproteins They contain a covalently linked lipid molecule – Long-chain fatty acids – Isoprenoids – Sterols – Glycosylated phosphatidylinositol (PGI) The lipid part can become part of the membrane The protein is now anchored to the membrane – reversible process – allows targeting of proteins – Some, such as GPI anchors are found only on the outer face of plasma membrane Sterols Have Four Fused Carbon Rings sterols = structural lipids present in the membranes of most eukaryotic cells steroid nucleus: – consists of four fused rings – almost planar – relatively rigid  Sterols and Sterol Cholesterol – steroid nucleus: four fused rings – hydroxyl group (polar head) in the A-ring – various nonpolar side chains The tetracycle structure of sterols is almost planar.  Choleste rol cholesterol = major sterol in animal tissues – amphipathic – polar head group – nonpolar hydrocarbon body – membran e constituen ts – similar to stigmasterol in  Sterols Serve as Precursors for Products with Specific Biological Activities steroid hormones regulate gene expression bile acids = polar derivatives of cholesterol that emulsify dietary fats in the intestine to make them more readily accessible to digestive lipases  Physiological Role of Sterols Cholesterol and related sterols are present in the membranes of most eukaryotic cells. – modulate fluidity and permeability – thicken the plasma membrane – no sterols in most bacteria Mammals obtain cholesterol from food or synthesize it de novo in the liver. Cholesterol, bound to proteins, is transported to tissues via blood vessels. – Cholesterol in low-density lipoproteins tends to deposit and clog arteries. Many hormones are derivatives of