Lipids PDF

Nutritional Biochemistry Lipids DIET413/BHCS1019 Dr Nathaniel Clark FHEA RNutr MRSB [email protected] 1 Last time - Quiz 1. Account for the origin of the term 1. Carbon hydrate = (C + H2O )n. carbohydrate....

Nutritional Biochemistry Lipids DIET413/BHCS1019 Dr Nathaniel Clark FHEA RNutr MRSB [email protected] 1 Last time - Quiz 1. Account for the origin of the term 1. Carbon hydrate = (C + H2O )n. carbohydrate. 2. Aldose-ketose, epimers, aldose-ketose, anomers. 2. Indicate whether each of the following pairs 3. Glucose is reactive because of the of sugars consist of anomers, epimers or an presence of an aldehyde group in its aldose-ketose pair: open-chain form. The aldehyde group D-glyceraldehyde and dihydroxyacetone. slowly condenses with amino groups to form bonds with haemoglobin. D-glucose and D mannose. 4. Two monosaccharides joined together D-glucose and D-fructose. to form a disaccharide using the alpha α-D-glucose and β-D-glucose. anomeric carbons. The left molecule is glucose, and the right fructose, which 3. Glucose reacts with haemoglobin and other makes the disaccharide sucrose. The H proteins to form covalent compounds. Why position is cis with the methanol group, is glucose reactive? meaning it is an alpha formation, but beta for fructose. The bond, a 4. Briefly describe what you see in the image – glycosidic bond, is formed through the include as much detail as possible. C1 of the glucose molecule and the C2 of the fructose. Glucose is in a pyranose ring and fructose in a furanose ring. 2 Previously Carbohydrates have a minimum of 3 carbon atoms and are in the ratio of (CH2O)n. They (except for dihydroxyacetone) can exist as isomers. Glucose, fructose, ribose, mannose and galactose are common monosaccharides. Exist in linear or cyclic versions. α and β versions exist of the rings, depending on OH orientation and can be pyranose or furanose. They form a hemiacetal or hemiketal. Disaccharide formation involves a glycosidic bond, and the end sugar of a polysaccharide can be a reducing sugar (open and closed form). Complex polysaccharides exist of glycogen, starch and cellulose. Glycoproteins are frequent in the body and have 3 different categories. 3 Learning outcomes 1. Describe the structure of fat molecules. 2. Understand the types of fat in foods are different due to their structure that gives rise to different properties. 3. Briefly describe the name and numbering system used for fats. 4. Describe phospholipid structure and understand how their molecular diversity arises (linked to Lecture 7). 5. Glycolipids and cholesterol are important membrane lipids (linked to Lecture 7). 6. Describe how amphipathic properties gives rise to a bilayer. 4 By the end... Hopefully, you will be able to understand papers that used specific nomenclature for lipids. We will build up to understanding this by the end of the first half. In this example, various fatty acids are being measured in human milk samples. The body has an incredible way of managing itself and can change in response to needs. Some compounds/molecules change depending on the state e.g. disease. 5 What can you tell me about these structures? 6 1. Lipids Lipids are the one class of large biological molecules that does not include true polymers, and they are generally not big enough to be considered macromolecules. The compound's called lipids are grouped together because they share one important trait: they mix poorly, if at all, with water. The hydrophobic behaviour of lipids is based on their molecular structure (Lecture 3). Although they may have some polar bonds associated with oxygen, lipids consist mostly of hydrocarbon regions. Lipids are varied in form and function but the most biologically important are fats, phospholipids, glycolipids and steroids. 7 Activity: complete the following 8 1. Fats Although fats are not polymers, they are large molecules assembled from a few smaller molecules by dehydration reactions – what is lost? A fat is constructed from two kinds of smaller molecules: glycerol and fatty acids. Glycerol is an alcohol with three carbons, each with a hydroxyl group. 9 1. Fats – fatty acids The fatty acid hydrocarbon tail can be short, medium or long (Note, not all atoms labelled here). 16 or 18 carbon atoms in length is the most common (14-24 found in biological systems). The dominance of fatty acid chains containing an even number of carbon atoms is in accord with the way in which fatty acids are biosynthesised (Jane’s Lectures). 10 1. De novo lipogenesis DNL is a metabolic process that converts nonlipid carbon precursors into lipids. Use of glucose into citrate to form Acetyl-CoA leading to the involvement of fatty acid synthase from M- CoA. 11 1. Putting “acid” in “fatty acid” The carbon at one end of the fatty acid is part of a carboxyl group, the functional group that gives these molecules the name fatty acid. Attached to the carboxyl group is a long hydrocarbon chain. The relatively nonpolar carbon-hydrogen bonds in the hydrocarbon chains of fatty acids are the reason fats are hydrophobic (Lecture 3). Fats separate from water because the water molecules hydrogen-bond to one another and exclude the fats. This is the reason that vegetable oil (a liquid fat) separates from the aqueous vinegar solution in a bottle of salad dressing. 12 1. Fats - structure Two structural components. In making a fat, three fatty acid molecules each join to glycerol by an ester linkage (C-O bond), a bond between a hydroxyl group (glycerol) and a carboxyl group (fatty acid). The resulting fat, also called a triacylglycerol, consists of three fatty acids linked to one glycerol molecule. The word triglyceride is often used on food packaged = same. 13 1. Fatty acid saturation Fatty acids vary in length and in the number and locations of double bonds. The terms saturated fats and unsaturated fats are commonly used in the context of nutrition. Refer to the structure of the hydrocarbon chains of the fatty acids. If there are no double bonds in the alkyl (hydrocarbon) chain, then as many hydrogen atoms as possible are bonded to the carbon skeleton. Such a structure is saturated with hydrogen, so the resulting fatty acid is called a saturated fatty acid. Depicted in different ways – 3D tetrahedral structure causes “wonky” structure. 14 1. Fatty acid unsaturation An unsaturated fatty acid has one or more double bonds, formed by the removal of a hydrogen atom from the carbon skeleton. The fatty acid will have a kink in its hydrocarbon chain where a cis double bond occurs. The configuration of the double bonds in most unsaturated fatty acids is cis. Why the preference for cis? 15 2. Animal fats A fat made from saturated fatty acids is called a saturated fat. Most animal fats are saturated. The hydrocarbon chains of their fatty acids – the “tails” of the fat molecules – lack double bonds, and their flexibility allows the fat molecules to pack together tightly. Saturated animal fats (such as lard and butter) are solid at room temperature. 16 2. Vegetable/fish fats In contrast, the fats of plants and fishes are generally unsaturated, meaning that they are built of one or more types of unsaturated fatty acids. Usually liquid at room temperature, plant and fish fats are referred to as oils – olive oil and cod liver oil. The kinks where the cis double bonds are located prevent the molecules from packing together closely enough to solidify at room temperature. 17 2. Science behind observations The properties of fatty acids and lipids derived from them are markedly dependent on chain length and degree of saturation. Unsaturated fatty acids are liquid at room temperature. Therefore, they have lower melting points than saturated fatty acids of the same length. For example, the melting point of stearic acid is 69.6 oC whereas that of oleic acid (which contains one cis double bond) is 13.4oC. 18 2. Science behind observations (2) The melting point of polyunsaturated fatty acids of the C18 series are even lower. Linoleic acid Chain length also affect melting points: palmitic acid (C16) is 6.5 degrees lower than that of stearic acid (C18). Shorter length = lower melting point. Thus, short chain length and unsaturation enhance the fluidity of fatty acids and of their derivatives. 19 2. Hydrogenated fats The phrase “hydrogenated vegetable oils” on food labels means that unsaturated fats have been synthetically converted to saturated fats by adding hydrogen. In a hydrogenation reaction, the fat reacts with hydrogen in the presence of a metal catalyst. The hydrogenation reaction reduces the number of double bonds in the fatty acid. If all the double bonds are turned into single bonds, then a saturated, hydrogenated fat is formed. Peanut butter and margarine are (partially) hydrogenated to prevent lipids from separating out in liquid. 20 2. Diet and atherosclerosis A diet rich in saturated fats is one of several factors that may contribute to the cardiovascular disease, atherosclerosis. Deposits called plaque develop within the blood vessel walls, causing bulges that impede blood flow and reduce resilience of the vessel. Studies have shown that the process of hydrogenating vegetable oils produces not only saturated fats but also unsaturated fats with trans double bonds. These trans fats may contribute to atherosclerosis and other problems. 21  2. Fats: an overview Also unsaturated! 22 2. The role of fats Fat has such a negative Components of gasoline connotation in our culture that you might wonder why we need it. The major function of fats is energy storage. The hydrocarbon tails of fats are like gasoline molecules and just as rich in energy. A gram of fat stores more than twice as much energy as a gram of polysaccharide such as starch. 23 2. Portable combustion Animals must carry energy stores with them, so there is an advantage to having a more compact reservoir of fuel – fat. Humans store it in adipose cells, which swell and shrink as fat is deposited and withdrawn from storage. In addition to storing energy, adipose tissue also cushions such vital organs as the kidneys, and a layer of fat beneath the skin that insulates the body. 24 2. Interactions of lipids and glucose Often think/taught about macromolecules in isolation. Need to be aware they can influence one another. Excess lipid accumulation can impact glucose metabolism by skeletal muscle and the pancreas. Promotes insulin resistance and type II diabetes. 25 3. Fatty acid names The systematic name for a fatty acid is derived from the name of its parent hydrocarbon by the substitution of “oic” for the final “e”. For example, the C18 saturated fatty acid is called octadecanoic acid because the parent hydrocarbon is octadecane. Butane. A C18 fatty acid with one double bond is called octadecenoic acid; with two double bonds octadecadienoic acid; and with three double bonds, octadecatrienoic acid. Placement of bonds can change. Butene. 26 3. Fatty acid names (2) The notation 18:0 denotes a C18 fatty acid with no double bonds, whereas 18:2 signifies that there are two double bonds. The structure of the unionized forms of two common fatty acids, palmitic acid and oleic acid are shown. The double bonds in polyunsaturated fatty acids are separated by a least one methylene group (CH2). 27 3. Carbon numbering Fatty acid carbon atoms are numbered starting at the carboxyl terminus. Carbon atoms 2 and 3 are often referred to as α and β, respectively. The position of a double bond is represented by the symbol Δ (delta) followed by the superscript number. For example, cis-Δ9 means that there is a cis double bond between carbon atoms 9 and 10. Trans-Δ11 means that there is a trans double bond between carbon 11 and 12. 28 3. Carbon numbering (2) Alternatively, the position of a double bond can be denoted by counting from the distal end, with the ω-carbon atom (methyl carbon) as number 1. Fatty acids are ionized at physiological pH, and so it is appropriate to refer to them according to their carboxylate form; e.g., palmitate. https://www.youtube.com/watch ?v=NLkOuegnPD4 29 3. Fatty acids – omega 3’s 30 3. Fatty acid nomenclature 31 Summary 1 Fats are composed of glycerol and fatty acid tails via an ester linkage. The fatty acids can be saturated (animal) or unsaturated (vegetable) with hydrogens – double bonds in the latter. The degree of saturation affects the physical properties of the fat (e.g., melting point). The degree of H found can be altered – hydrogenated fats. Notation can denote the number of double bonds (e.g., 18:0, 18:2). Fatty acid carbon atoms are numbered starting at the carboxyl terminus. Δ or ω denotes where a double bond is found in an unsaturated fatty acid (depending on the starting carbon). 32 10-minute break 33 Activity C20:5 Δ 5, 8, 11, 14, 17 C22:6 Δ 4, 7, 10, 13, 16, 19 C20:4 Δ 5, 8, 11, 14 Using the delta and omega numbering system, what is the name of these compounds according to their convention? Identify the end of the molecule. Where do you start with for delta and omega numbering? How many double bonds are present? Based on the omega name, what are they? 34 4. Phospholipids https://www.youtube.com/watch?v=Q 67goxABqKk versus Phospholipids are essential for cells because they form cell membranes. Their structure provides a classic example of how form first functions at the molecular level (system level = DIET414/BHCS1020). A phospholipid molecule is constructed from four components: One or more fatty acids. A platform to which the fatty acids are attached. A phosphate group. An alcohol attached to the phosphate. 35 4. Identifying lipid structures These are commonly found structures in lipids – what is the difference between these molecules? These are all glycerol. Compared to amino acids and carbohydrates, the depiction of lipids is more complicated and changes. It’s helpful if you can understand what you are looking at. We’ve considered the fatty acid chain, which is relatively straight forward compared to parts of the head molecule. 36 4. Phosphoglycerides The fatty acid component provides a hydrophobic barrier, whereas the remainder of the molecule has hydrophilic properties that enable interaction with the aqueous environment. The platform on which phospholipids are built may be glycerol, a three-carbon alcohol, or sphingosine, a more complex alcohol. Note the different length. Phospholipids derived from glycerol are called phosphoglycerides. 37 4. Phosphoglycerides (2) A phosphoglyceride consists of glycerol backbone to which are attached two fatty acid chains and a phosphorylated alcohol. In phosphoglycerides, the hydroxyl groups at C-1 and C-2 of glycerol are esterfied (C-O bond) to the carboxyl groups of the two fatty acid chains. Term “esters” is for a condensation reaction between an alcohol and a carboxylic acid. The C-3 hydroxyl group of the glycerol backbone is esterfied to phosphoric acid. 38 4. Phosphatidate When no further additions are made, the resulting compound is phosphatidate (diacylglycerol 3-phosphate), the simplest phosphoglyceride. Only small amounts of phosphatidate are present in membranes. However, the molecule is a key intermediate in the biosynthesis of the other phosphoglycerides – what is it missing? Structure is shown here (twice) – the R groups are the acyl groups (O=C-R 2) with fatty acid hydrocarbon chains. 39 4. Alcohol groups The major phosphoglycerides are derived from phosphatidate by the formation of an ester bond between the phosphate group of phosphatidate and the hydroxyl group of one of several alcohols. The common alcohols of phosphoglycerides are the amino acid serine, ethanolamine, choline, glycerol and inositol. 40 4. Phospholipid head - diversity The structural formulas of these groups attached as phospholipids can be seen here. What does zwitterionic mean? Why is this beneficial? Note, LPC has also been included but not mentioned prior. Name derived from the parent, phosphotidate. E.g., phosphotidylcholine. Messenger in cell signalling (DIET414/BHCS1020). https://www.youtube.com/wa tch?v=CBEys2CTkgE (OT) 41 4. Sphingomyelin Sphingomyelin is a phospholipid found in membranes that is not derived from glycerol. Based on the name, where is it found? Instead, the backbone is sphingosine, an amino alcohol that contains long, unsaturated hydrocarbon chain. In sphingomyelin, the amino group of the sphingosine backbone is linked to a fatty acid by an amide (or peptide) bond. In addition, the primary hydroxyl group of sphingosine is esterfied to phosphorycholine (hydrophilic polar head group). 42 5. Membrane lipids can include carbohydrates After phospholipids, the second major class of membrane lipids, glycolipids, are sugar-containing lipids. Like sphingomyelin, the glycolipids in animal cells are derived from sphingosine. In glycolipids, one or more sugars are attached. The simplest glycolipid, called cerebroside, contains a single sugar residue, either glucose or galactose. More-complex glycolipids, such as gangliosides, contain branched chain of as many as seven sugar residues. Glycolipids are oriented in a completely asymmetric fashion with the sugar residues always on the extracellular side of the membrane (lecture 7). 43 5. Steroids In cholesterol, a hydrocarbon tail is linked to the steroid at one end, and a hydroxyl group is attached at the other end. In membranes, the orientation of the molecule is parallel to the fatty acid chains of the phospholipids, and the hydroxyl group interacts with the nearby phospholipid head groups. Many hormones, as well as cholesterol, are steroids, which are lipids characterised by a carbon skeleton consisting of four fused rings. 44 5. Steroids 2 Different steroids vary in the chemical groups attached to this ensemble of rings. Cholesterol is a common component of animal cell membranes (3rd most common) and is also the precursor from which other steroids are synthesised. In vertebrates, cholesterol is synthesised in the liver. Both saturated fats and trans fats exert their negative impact on health by affecting cholesterol levels. 45 6. A membrane lipid is amphipathic However, lipids possess a critical common structural theme: membrane lipids are amphipathic molecules. A membrane lipid contains both a hydrophilic and hydrophobic moiety. Membrane formation is a consequence of the amphipathic nature of the molecules. Their polar head groups favor contact with water, whereas their hydrocarbon tails interact with one another in preference of water. In aqueous solutions, lipids can form a globular structure called a micelle. The polar head groups form the outside surface of the micelle, which is surrounded by water, and the hydrocarbon tails are sequestered inside, interacting with one another. 46 6. Bilayer formation Alternatively, the strongly opposed preferences of the hydrophilic and hydrophobic moieties of membrane lipids can be satisfied by forming a lipid bilayer, composed of two lipid sheets. Also called a bimolecular sheet. The hydrophobic tails of each individual sheet interact with one another, forming a hydrophobic interior that acts as a permeability barrier. The hydrophobic head groups interact with the aqueous medium on each side of the bilayer. 47 6. Micelle versus bilayer The favored structure for most phospholipids and glycolipids in aqueous media is a bimolecular sheet rather than a micelle. Separates hydrophobicity. The reason is that the two fatty acid chains of a phospholipid or a glycolipid are too bulky to fit into the interior of the micelle. In contrast, salts of fatty acids (such as sodium palmitate, a constituent of soap) readily forms micelles because they contain only one chain. Important for fat digestion (DIET414/BHCS1020). 48 6. Phospholipid bilayer formation The formation of bilayers over micelles by phospholipids is of critical biological importance – cell membranes. A micelle is a limited structure, usually less than 20 nm in diameter. In contrast, a bimolecular sheet can extend to macroscopic dimensions, as much as a millimeter or more. Lipid bilayers form spontaneously by a self- assembly process. E.g., oil and water (Lecture 2 In other words, the structure of a bimolecular sheet is inherent in the structure of a constituent lipid molecules. 49 6. Phospholipid bilayer bonds van der Waals attractive forces between the hydrocarbon tails favor close packing of tails. Electrostatic and hydrogen- bonding attractions between the polar head groups and water molecules. Lipid bilayers are stabilized by the full array of forces that mediate molecular interactions in biological systems. 50 6. Phospholipid bilayer consequences Because lipid bilayers are held together by many reinforcing, noncovalent interactions (predominantly hydrophobic), they are cooperative structures. These hydrophobic interactions have three significant consequences: 1. Lipid bilayers have an inherent tendency to be extensive. 2. They tend to close on themselves so that there are no edges. Controls movement (Lecture 7). 3. They are self sealing because a hole in a bilayer is energetically unfavorable. 51 Summary 2 A phospholipid molecule is constructed from four components. The platform on which phospholipids are built may be glycerol or sphingosine (or a more complex alcohol). Phosphotidate is the simplest phophoglyceride and is mainly used as a precursor for other phospholipids. The head group gives structural diversity to phospholipids. Glycolipids are the second major type of membrane lipid (after phospholipids), and steroids are the third most common (cholesterol). Membrane lipids are amphipathic which facilitates the formation of micelles, bilayers (phospholipid bilayer) and vesicles for various cellular functions. 52 Questions 1. What is one characteristic that all lipids have in common? 2. What is the structure of glycerol? Which functional group does it contain? 3. Compare the structure of a fat (triglyceride) with that of a phospholipid. 4. Why are human sex hormones considered lipids? 5. Suppose a membrane surrounded an oil droplet. Describe and explain the form it might take. 6. How many phospholipid molecules are there in a 1 µm2 region of a phospholipid bilayer membrane? Assume that a phospholipid molecule occupies 70 Å2 of the surface area. 53 Before next time... Consult textbooks for further reading. Re-read the lecture notes from today. Read the next sessions lecture notes before attending. Definitions for next time: dissociation, covalent, ions Lecture 4, Lecture 6. Further reading: Campbell and Reece, Biology, Chapter 5. Lodish et al., Molecular cell biology, Chapter 5. Berg et al., Biochemistry, Chapter 12. 54