CLASS: 11:00-11:50 Scribe: Eric Larson

CLASS: 11:00-11:50 Scribe: Eric Larson Wednesday, September 1st Proof: Angi Gullard PROFESSOR: Whikehart LIPIDS, STRUCTURES AND TYPES Page 1 of 5

I. Intro – Lipids [S1] a. Goal is to survey four lipid types and tell us a little about what each does II. Four Groups of Lipids [S2] a. We’ll discuss four groups of lipids: i. Fatty acids: lipid building blocks for triacylglycerides and sphingolipids (are not building blocks for cholesterol) ii. Triacylglycerides and phospholipids: triacylglycerides are used for energy storage, and phospholipids are utilized in membranes iii. Sphingomyelins: mysterious to the scientific community until recently iv. Cholesterol and derivatives: used to make steroids and other various compounds III. Essential Information [S3] a. Fats are lipids, but not all lipids are fats b. Both substances are soluble in non-polar solvents like benzene and xylene c. Know the different meanings of lipids and fats i. Fats are esters that are made from fatty acids and glycerol ii. Lipids are compounds soluble in non-polar solvents but don’t have to be esters (ex. gasoline, jet engine fuel) d. Fats used for energy storage and insulation IV. Untitled [S4] a. Be careful how you use the terms “lipid” and “fat” b. All compounds here are lipids, but not necessarily fats V. Some Examples of Lipids [S5] a. Cholesterol is a lipid, but not a fat, because it doesn’t have glycerol b. Tristerarin is a fat, because it is an ester of fatty acids and has a glycerol VI. Why Are Lipids Important? [S6] a. Lipids are important because: i. They are a significant source of fuel and energy ii. They form borders for cells and sub cellular organelles within cells iii. They are sources of hormones and vitamins VII. Untitled [S7] a. Triacyglycerol is used for fuel for heart tissue. Contrary to common belief, glucose is not more important as the fuel for heart tissue i. Triacylglycerols are important under starvation conditions, because this fat is broken down slowly for metabolism b. Phospholipids are used to maintain plasma membranes c. Cholesterol is used as a precursor for many hormones VIII.Lipid Solubility Characteristics [S8] a. Important to have some understanding of this b. Lipids are water hating compounds, or hydrophobic, because they are non-polar; they have no partial charge c. It is energetically favorable to reduce contact with polar substances such as water, which is why lipids and water don’t mix (oil and water separation given as an example) d. Of course, there are exceptions: some lipid molecules (such as fatty acids) have a charged portion, such as a charged tail, which makes them compatible with water i. Lipids which have both water soluble and water insoluble portions are named amphipathic – important in cell membranes IX. What Exactly Is a Hydrophobic Bond? [S9] a. When a bunch of lipids get together they form hydrophobic bonds b. Know that a hydrophobic bond is not a true bond i. It is group of non-polar compounds which associate to minimize contact polar substances, such as water, which ultimately allows for the most energetically favorable situation c. Structures called micelles will form when groups of fatty acids associate with their carboxylic acids facing towards the polar water environment, and their alkyl groups facing inwards to reduce exposure to polar substances i. This is in a sense a primitive membrane d. What if you have a lipid with no hydrophilic regions? i. You would get something similar, but with no micelle formation, just lipids separating into their own phase X. Two Non-Polar Solvents [S10] a. Two non-polar solvents, cyclohexane and heptane CLASS: 11:00-11:50 Scribe: Eric Larson Wednesday, September 1st Proof: Angi Gullard PROFESSOR: Whikehart LIPIDS, STRUCTURES AND TYPES Page 2 of 5 b. Heptane was originally used in gasoline until longer carbon chain forms replaced it

XI. Fatty Acids: Lipid Building Blocks [S11] a. Fatty acids are composed of a hydrocarbon tail and a carboxylic head b. They can be named using IUPAC nomenclature, as well as common nomenclature i. In the case of dodecanoic acid, the IUPAC name is nothing more than a Greek number (dodekanos meaning twelve), and the common name (laurus) was chosen because this compound was first isolated from a laurel plant XII. Untitled [S12] a. These examples are here to show you different forms of fatty acids b. A fatty acid can be saturated – meaning it has no double bonds (palmitic acid and stearic acid) c. A monounsaturated fatty acid, is one with a single double bond i. This double bond subsequently makes a kink in the chemical structure ii. This kink, when present in a cellular membrane, creates more disorder in the membrane which makes it more flexible d. It is not uncommon for many membrane fatty acids to have as many as 6 double bonds XIII. Fatty Acid Facts [S13] a. Fatty acids have both IUPAC and common names b. Fatty acids partially deionize, and can be used to make buffers c. Most biological fatty acids are usually 12-24 carbons long d. They are usually completely saturated or have one or ore double bonds e. Carbon length increases melting point f. Increasing the degree of unsaturation decreases melting point g. This flexibility of fatty acids is important because it can impart hardness or flexibility to cellular membranes, depending on the requirements of the individual XIV. Effects of Saturation and Carbon Lengths on Melting Points of Fatty Acids [S14] a. This is an interesting chart that shows the number of carbon atoms in a fatty acid versus the melting point b. If you use a completely saturated fatty acid, the curve goes up c. One double bond and the melting point greatly decreases d. Four double bonds and it is very decreased e. You can mix and match these to get a membrane that is ideal for a particular cell XV. Some Shorthand Naming [S15] a. Lauric acid has 12 carbons and no double bonds, so it is written in short hand as 12:0 b. Oleic acid has 18 carbons and 1 double bond, so it is written as 18:1 c. Linolenic acid has 18 carbons and three double bonds, so it is written as 18:3 i. The positions of the double bonds, counting from the carboxylic end of the molecule, can also be indicated in short hand by writing  followed by the carbon number of the double bond ii. In the case of linolenic acid, it would be written 18:3 9,12,15 XVI. Untitled[S16] a. The chemical structure of linoleic acid b. It is 18 carbons long, so it can be written as 18:3 i. Or 18:3 9,12,15 c. If we wanted to call it an omega fatty acid, we would call it omega-3 fatty acid, meaning the first double bond begins from the 3rd carbon out XVII. Untitled [S17] a. Not addressed – wasn’t in his slides

XVIII. Commercial Hydrogenation [S18] a. Cis and trans configuration refers to whether we have similar substituents on the same side of the double bond (CIS) or on opposite side (TRANS) b. This is significant because in a commercially utilized process called a hydrogenation reaction used to convert double bonds into single bonds) side reactions can occur c. These side reactions create trans fatty acids which increase the LDL lipids (low density lipoproteins) i. LDLs are a mixture of proteins and lipids – this is a transport form for lipids ii. These are known as the “bad cholesterol” XIX. Saturated vs. Unsaturated Fatty Acids [S19] a. Saturated fatty acids are bad to have in your diet – problems with LDLs b. This chart shows is an indicator of the kind of unsaturated vs. saturated fatty acids that you find in different organic sources CLASS: 11:00-11:50 Scribe: Eric Larson Wednesday, September 1st Proof: Angi Gullard PROFESSOR: Whikehart LIPIDS, STRUCTURES AND TYPES Page 3 of 5 c. Pork and milk are high in saturated fatty acids d. Coconut oil is very high in saturated fatty acids too e. He referenced his bottle of canola oil i. Explained how it got a bad reputation, but that reputation has been proven to be a myth XX. Two Issues Concerning Consumption of Fatty Acids [S20] a. Two issues concerning consumption of fatty acids i. Too much intake of saturated fatty acids (beef and butter) ii. Too much intake of trans-fatty acids (such as margarine made by hydrogenation) b. Trans fatty acids can be found in many things i. Cake mixes can have a lot of trans fatty acids due to hydrogenation, which is something to watch out for XXI. Analysis of Fatty Acids [S21] a. This is an old manual method of analyzing fatty acids i. Take a piece of tissue, such as liver, and homogenize it in a mixture of chloroform, water, and methanol ii. Put in a separatory funnel iii. You would shake the funnel and allow it to separate into different phases iv. Various lipids would appear in various phases v. Take them out and put them through some type of (absorption, or thin-layer) chromatography and different lipid classes would separate based on charges (thin layer chromatography for example) vi. Treat these separated fatty acids with NaOH and methanol to produce fatty acyl methyl esters (this process is called transesterification) vii. Finally, you can process those esters through a chromatographic apparatus (either gas-liquid or high performance liquid chromatography) , and burn what comes out in a hydrogen flame 1. The hydrogen flame would produce a peak, and depending on the time at which the substance came out, you could identify if it was a C-14 or C-16 fatty acid- you would have an analysis of which fatty acids are present b. Study this process – expected to know it XXII. Stored Fat: Triacylglycerols (TGs) [S22] a. When fat is stored, it is stored in cells called adipocytes i. These adipocytes store fat in the form of triacylglycerol b. Triacylglycerols (TGs) are 3 fatty acids which are attached to a glycerol molecule by an enzyme (acyltransferase) c. Adipocytes store huge amounts of TGs; adipocytes are always there – cells either increase or decrease in size based on dietary habits XXIII. TG Facts [S23] a. TGs are mixed in chain length and degree of saturation (important for membranes) b. Energy obtained in metabolic oxidation of TGs is 2.2x that of proteins and carbohydrates - you can get more energy from these (even though you can get energy more quickly from carbohydrates and proteins; better source of energy) c. Important as a temperature insulator XXIV. Saponification (Fat Hydrolysis) [S24] a. TGs are broken down by fat hydrolysis i. The artificial lab process is called saponification b. You can do it with a little animal fat and wood ash - the end product is soap i. Potassium salts give you a soft soap ii. Sodium salts gives you a hard soap iii. All you need is a triglyceride and these ingredients plus some heat, and by the process of saponification you get soap c. Cells use lipase to produce their own form of TG hydrolysis d. Lipases are omnipresent because fatty acids must be separated in order to transport them XXV. Structural Forms of Lipids [S25] a. There are three types of lipids used to form tissue structures and membranes i. Glycerophospholipids ii. Sphingolipids iii. Steroids XXVI. Glycerophospholipids [S26] a. Common name phospholipids b. They are a variation of TGs , which have substituted a polar head group for one of the fatty acid parts c. Ex. Phosphatidic acid (only 2 fatty acids and a phosphoric acid group) CLASS: 11:00-11:50 Scribe: Eric Larson Wednesday, September 1st Proof: Angi Gullard PROFESSOR: Whikehart LIPIDS, STRUCTURES AND TYPES Page 4 of 5 XXVII. Types and Nature of Head Groups [S27] a. This slide displays the molecules he drew on board – drawn to a larger size because these molecules are displayed relatively small on the slide i. P -inositol, P-serine, P-ethanolamine b. At least wants you to be familiar with the molecules on this slide i. Not familiar with the structures, rather with what they do c. There is a polar head group on each of these molecules, giving partial negative and positive charges similar to water molecules (arrows show polarity) i. This allows them to be very, very compatible with water d. So when these lipids make membranes, it is the polar head groups interacting with water molecules on the surface of the membrane i. That’s one important thing about phospholipids; the other important thing is their fatty acid tails XXVIII. Glycerophospholipids are Glycerol Units Which are Esterified [S28] a. Glycerophospholipids are glycerol units to which are esterified two fatty acids and one polar head unit b. You don’t have to know the structure of the polar head units, but you do have to know what they do c. The fatty acids are often mixed with one saturated and unsaturated; there are exceptions d. The polar heads are one of six common types, and choline and ethanolamine are the most common XXIX. Glycerophospholipids [S29] a. Phospholipids for most of us are utilized as membrane components b. Polar bears use phospholipids as insulators, fuel, and as a source of water i. Fatty acids can be utilized for water, by breaking them down into water molecules by a series of reactions XXX. Sphingolipids [S30] a. The name comes from Egyptian and Greek mythology i. The Sphynx was a creature that would ask riddles of people ii. This class of lipids was so named because the sphingolipid structure was unknown and eluded researchers for so many years, that they named this group after the cryptic Sphinx b. The hinge molecule, or base, for sphingolipids is the sphingosine molecule, and not glycerol XXXI. Examples of Some Sphingolipids [S31] a. Adding 1 fatty acid creates a ceramide b. If you now add something to the hydroxy group, you get sphingomyeline c. If you add a sugar group in place of the OH group you get cerebroside d. If you add a number of sugar groups it becomes a ganglioside e. These names are derived from where these lipids were originally found, which was nervous tissue XXXII. Where and Why are Sphingolipids Present? [S33] a. They are often found in nerve cells b. Sphingolipids have short chain sugars that act in a immunological fashion, as immunological identifiers for a cell type c. Sphingolipids act to make membrane tougher and more rigid XXXIII. A Note to Consider [S34] a. Degradation of gangliosides occurs in lysosomes b. If there is a deficiency of 1 or more degredative enzymes, you get a metabolic storage disease (rare; at least 30 types of these diseases exist) c. One example of such a disease is Tay-Sach’s (TS) disease i. These types of diseases rare, but do exist d. TS disease is caused when a ganglioside, GM2, is only partially degraded due to deficiency of the enzyme hexosaminidase A e. This causes the ganglioside to build up in the cell, until it eventually spills out causing symptoms such as joint problems, mental retardation, and eventually death XXXIV. Isoprene and Cholesterol [S35] a. The third and last class to be considered is cholesterol b. We are also considering isoprene, because it is used to synthesize cholesterol c. Generally, a pure cholesterol has no fatty acid components XXXV. Isoprene is a Dangerous Lipid [S36] a. Isoprene is normally a dangerous lipid b. It is colorless, flammable, and made from refining oil c. In the body, isoprene is complexed with acetyl CoA and maintained in a safe form XXXVI. Some Commonly Known Terpenes [S37] a. Terpenes are cousins to cholesterol i. Citronella is a well-known type of terpene CLASS: 11:00-11:50 Scribe: Eric Larson Wednesday, September 1st Proof: Angi Gullard PROFESSOR: Whikehart LIPIDS, STRUCTURES AND TYPES Page 5 of 5 ii. Other well-known terpenes are menthol, lycopene (red compound in tomatoes and carrots), all-trans-retinal, and coenzyme Q (UQ) XXXVII. Cholesterol [S38] a. Cholesterol is a steroid i. It has 4 fused rings b. It is a starting component for hormone synthesis c. It is important in the composition of plasma membranes i. It acts as a stiffening compound for plasma membranes XXXVIII. Untitled [S39] a. Diagram of the molecular composition of cholesterol b. The 3 blue arrows point out important points on the structure i. Arrow # 1: the hydroxyl group is often esterified to fatty acids to make cholesteryl esters ii. Arrow # 2: methyl groups off of AB and CD rings - can be modified or substituted to make significant changes to the properties of the molecule (add fluorine for example; derivatives of hormones) iii. Arrow # 3: the tail of the cholesterol molecule, when it undergoes changes to form hormones, is often shortened c. Cholesterol rings are often in the chair conformation (not boat conformation) because it is more energetically favorable XXXIX. Summary [S40] a. Know the properties of fatty acids (don’t need to know specific fatty acids) i. What happens with double bonds being added and that sort of thing b. Fats are stored as triacylglycerides c. Sphingomyelins, phospholipids, and cholesterol are all lipids incorporated into the membrane d. The properties of each class of lipid determines how it is used biologically

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