Introduction to Lipids

• Lipids are a family of substances that are insoluble in water but soluble in nonpolar solvents and solvents with low polarity such as diethyl ether.
• Lipids are the most diverse class of biochemicals.
• Lipids are defined more by their function than their structure.

Classification by Function

• Lipids have three major roles in human biochemistry.
• Lipids store energy within cells.
• They form parts of membranes separating cellular compartments of aqueous solutions.
• Lipids act as chemical messengers.

Lipid Use

• Used in the storage of energy, particularly in animals.
• Animals, including humans, store more energy as fat than as starch, which plants use.
• Burning fats produces more than twice the energy of carbohydrates, approximately 9 kcal/g compared to 4 kcal/g.

Membrane Components

• Lipids compose membranes that separate compartments containing aqueous solutions, which includes cells or organelles within them.
• Water insolubility arises because polar groups are smaller than nonpolar portions, providing water repellency or hydrophobic properties.

Messengers

• Lipids function as chemical messengers, with steroid hormones acting as primary messengers to deliver signals between body parts.
• Secondary messengers like prostaglandins and thromboxanes mediate hormonal responses.

Classification by Structure

• Lipids are classified into four groups for study purposes.
• These groups are simple lipids (fats, oils, waxes), complex lipids, steroids, and prostaglandins, thromboxanes, and leukotrienes.

Fatty Acids

• A fatty acid has a long, unbranched carbon chain with a carboxyl group at one end.
• Carboxyl group is hydrophilic and the hydrocarbon tail is hydrophobic.
• Fatty acids are amphipathic compounds.
• The carboxylic acid functional group is usually ionized under biological conditions.
• Fatty acids are insoluble in water due to the long carbon chain overshadowing the carboxyl group's hydrophilic nature.
• Most naturally occurring fatty acids contain an even number of carbon atoms.

Depicting Fatty Acids

• Line structures depict the molecules with each bend representing a carbon bonded to four other molecules.
• Only the carbon in the carboxyl group is explicitly shown.
• Double bonds between carbons are indicated by a second line.

Isolation

• Over 500 different fatty acids have been isolated from cells and tissues.
• Common names and condensed formulas are given for the most abundant fatty acids.
• The number of carbons in a fatty acid and the number of carbon-carbon double bonds are shown by two numbers separated by a colon.
• Linoleic acid is designated as an 18:2 fatty acid, showing that in the 18-carbon chain there are two double bonds.

Characteristics of Abundant Fatty Acids

• Nearly all have an even number of carbon atoms.
• Most have between 12 and 20 carbons in an unbranched chain.
• The three most abundant in nature are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1).
• The cis isomer predominates in unsaturated fatty acids.
• The trans isomer is rare.
• Unsaturated fatty acids have lower melting points than saturated counterparts.
• The greater the degree of unsaturation, the lower the melting point.

Melting Point

• The melting points of 18-carbon fatty acids vary.
• Stearic acid (18:0) melts at 70°C.
• Oleic acid (18:1) melts at 16°C.
• Linoleic acid (18:2) melts at -5°C.
• Linolenic acid (18:3) melts at -11°C.
• Linolenic acid with its three carbon-carbon double bonds has the lowest melting point of these four fatty acids.

Classification of Fatty Acids

• Fatty acids are classified into saturated and unsaturated groups.
• Saturated fatty acids contain only carbon-carbon single bonds in their hydrocarbon chains.
• Unsaturated fatty acids contain one or more carbon-carbon double bonds.
• The unsaturated fatty acids listed are the cis isomer.

States of Matter

• Saturated fatty acids are solids at room temperature because the regular nature of their hydrocarbon chains allows molecules to pack together closely.
• London dispersion forces are maximized with close packing.
• The longer the carbon chain-length of the fatty acid, the more energy is needed to melt them.
• All common cis unsaturated fatty acids are liquids at room temperature because chains do not pack regularly.
• Less energy is needed to melt them since London dispersion forces only act over shorter segments of the chains.
• The greater the degree of unsaturation, the lower the melting point.

Carbon Bonds

• The double bonds are isolated from each other by several singly bonded carbons.
• In arachidonic acid, there is a double bond at the ninth carbon atom from the carboxylic acid.
• Double bond position results from unsaturated fatty acid synthesis.
• When the double bond is measured starting with the carbonyl carbon, the designation A is used, where A⁹ indicates that the double bond is between the ninth and tenth carbon counting from the carbonyl carbon.

Fatty Acids in Plant and Animal Life

• Plant oils are liquid at room temperature because they have higher proportions of unsaturated fatty acids, unlike animal fats, which tend to be solids.
• Conversion of oils to fats via hydrogenation is a commercially important process.
• Hydrogenation is the process of adding hydrogen across the double bond of unsaturated fatty acids to produce saturated fatty acids.
• Oleomargarine uses partially hydrogenated vegetable oils, which tend to include trans fatty acids.
• Fatty acids are rarely found free in nature, but they form parts of many commonly occurring lipids.

Triglyceride Structure

• Animal fats and plant oils are triglycerides.
• Triglycerides are triesters of glycerol and fatty acids.
• Esters are made up of an alcohol part and an acid part; the alcohol of triglycerides is glycerol.
• Even-numbered acids are found in triglycerides because the body builds these acids from acetate units, adding carbons two at a time.
• In triglycerides (triacylglycerols) all three hydroxyl groups of glycerol are esterified.
• Mono- and diglycerides are less common however, with only one or two -OH groups of the glycerol being esterified by fatty acids.

Composition

• Triglycerides are complex mixtures, with molecules containing three identical fatty acids.
• Usually, two or three different acids are present.
• The hydrophobic character of triglycerides results from the long hydrocarbon chains of the fatty acid components.
• Ester groups (-C-O-C) are polar, but are buried in a nonpolar environment, making the triglycerides insoluble in water.

Physical State

• Animal fats are generally solid at room temperature, while those from plants or fish are usually liquids, though there are exceptions.
• Liquid fats are often called oils, but they are esters of glycerol like solid fats and are not petroleum products.
• The degree of unsaturation causes structural differences between solid fats and liquid oils.
• Solid animal fats contain mainly saturated fatty acids, whereas vegetable oils contain high amounts of unsaturated fatty acids.
• Some unsaturated fatty acids, like linoleic and linolenic acids, are essential fatty acids. They cannot be synthesized by the body, and must be consumed as part of the diet.
• Coconut oil has only a small amount of unsaturated fatty acids, but is a liquid because it is rich in low-molecular-weight fatty acids (chiefly lauric acid).
• Oils with an average of more than one double bond per fatty acid chain are called polyunsaturated.
• Pure fats and oils are colorless, odorless, and tasteless; the tastes, odors, and colors are caused by small amounts of other substances dissolved in the fat or oil.

Hydrogenation

• Reduces carbon-carbon double bonds to single bonds by treating them with hydrogen and a catalyst.
• Allows conversion of unsaturated liquid oils to solids.
• Used on a large scale to produce solid shortening, but hydrogenation is carefully controlled to avoid complete saturation (such as Crisco).
• Results in partially hydrogenated vegetable oils and is the source of trans fatty acids.

Membranes

• Fats and oils differ in the triglycerides and phosphoglycerides of membranes. This difference is very important, more then the length of the fatty acid chain affecting the melting point.
• Butter has a high proportion of short-chain fatty acids and melts in the mouth.
• Membranes must maintain a certain degree of fluidity to be functional.
• Unsaturated fats are distributed in varying proportions in different parts of the body.
• Membranes of internal organs of warm-blooded mammals have a higher percentage of saturated fats than skin tissues to maintain solidity at higher temperatures.
• When bacteria are grown at different temperatures, the fatty acid composition of the membranes reflects more unsaturated fatty acids at lower temperatures and more saturated fatty acids at higher temperatures.
• Because cardiovascular disease is correlated with diets high in saturated fats, a diet of more unsaturated fats may reduce the risk of heart attacks and strokes.
• Trans fatty acids raise the ratio of LDL cholesterol compared to HDL cholesterol potentially resulting in a positive correlator of heart disease.

Properties of Triacylglycerols

• The triglycerides are the most common lipid materials. In the latter two types, only one or two -OH groups of the glycerol are esterified by fatty acids.
• Triglycerides are complex mixtures. Some molecules contain three identical fatty acids, but most cases involve two or three different acids.
• The hydrophobic character of triglycerides is attributed to the long hydrocarbon chains of the fatty acid components. The ester groups bury themselves in the nonpolar environment, making the triglycerides insoluble in water.

Labels and FDA Implications

• Labels highlight the absence of "trans fats" in products.
• A preliminary determination by the Food and Drug Administration (FDA) declared that trans fats are not "generally recognized as safe".
• Diets containing trans fats lead to high serum cholesterol levels and a higher ratio of low-density lipoprotein (LDL) to high-density lipoprotein (HDL), which creates well known risk factors for heart disease.
• Substances that are "generally recognized as safe" (GRAS) are not subject to regulation as food additives. The preliminary determination by the FDA makes it likely that trans fats will be classified as food additives and be subject to regulation.

Structures of Complex Lipids

• Triglycerides are relevant components of fate storage cells. Complex lipids are significant components of membranes.
• Complex lipids are classified into phospholipids and glycolipids.
• Phospholipids contain an alcohol, two fatty acids, and a phosphate group (further divided into Glycerophospholipids and sphingolipids).
• Glycolipids are complex lipids that contain carbohydrates.

Lipids and Membrane Structure

• Complex lipids form the membranes around cells and small structures called organelles.
• Unsaturated fatty acids are important components of these lipids, so most lipid molecules in the bilayer containing at least one unsaturated fatty acid.
• Cell membranes separate cells from the external environment and provide selective transport for nutrients and waste products into and out of cells.
• Membranes are made from lipid bilayers, where two rows (layers) of complex lipid molecules are arranged tail to tail.
• Hydrophobic tails point toward each other so they are as far away as possible from water, and the hydrophilic heads project to the inner and outer surfaces of the membrane.
• Cholesterol, as a membrane component, is largely hydrophobic with a small polar portion oriented towards the inner and outer surfaces of the membrane.

Fluidity

• Unsaturated fatty acids prevent tight packing of the hydrophobic chains, thereby providing a liquid-like character to the membranes.
• Products of the body's biochemical processes must cross the membrane, and the liquid nature of the lipid bilayer allows such transport.
• Lipid part of the membrane acts as a barrier against movement of ions or polar compounds into and out of the cells.
• Protein molecules are either suspended on the surface (peripheral proteins) or partly or fully embedded in the bilayer (integral proteins).
• There has been extensive study on lipid and protein components and electron microscopic studies have provided evidence that the complex lipids that make up the bilayer are not distributed evenly.

Glycerophospholipids

• Glycerophospholipids are similar to fats and used as membrane components of cells throughout the body.
• Backbone contains a glycerol, and two of its three hydroxyl groups are esterified by fatty acids.
• In most glycerophospholipids, the fatty acid on carbon 2 of glycerol is unsaturated.
• The third group is esterified not by a fatty acid, but by a phosphate group, which is also esterified to another alcohol.
• If the other alcohol is choline, a quaternary ammonium compound, the glycerophospholipids are called phosphatidylcholines (lecithin).

Lecithin Features and Examples

• Lecithin molecule contains stearic acid on one end and linoleic acid in the middle. Other lecithin molecules contain other fatty acids, but the one on the end is always saturated and the one in the middle is always unsaturated. Lecithin is a major component of egg yolk, includes both polar and nonpolar portions within one molecule, and is an excellent emulsifier.
• Lecithin has a negatively charged phosphate group and a positively charged quaternary nitrogen from the choline.
• The charged parts of the molecule provide a strong hydrophilic head, while the rest of the molecule is hydrophobic, which means the hydrophobic tail of a lecithin is part of a lipid bilayer points toward the middle of the bilayer and the hydrophilic heads line both the inner and outer surfaces of the membranes.
• Other glycerophospholipids are the cephalins which are similar to the lecithins in every way except they contain other alcohols such as ethanolamine or serine in place of choline.
• Another group is phosphatidylinositols (PI), where the alcohol inositol is bonded to the rest of the molecule by a phosphate ester bond and not only are integral structural parts of the biological membranes, but also, in their higher phosphorylated form, act as signaling molecules.

Sphingolipids

• Myelin, the coating of nerve axons, contains sphingolipids, in which the backbone is sphingosine:

Sphingosine Structure

• A long-chain fatty acid is connected to the —NH₂ group by an amide bond.
• Combination of a fatty acid and sphingosine is called the ceramide portion of the molecule.
• Ceramide can be found in cerebrosides
• Ceramide may contain different fatty acids.
• Stearic acid occurs mainly in sphingomyelin.
• The distinguishing feature of a sphingomyelin is that the terminal hydroxyl of the sphingosine is esterified to a phosphorylcholine or phosphorylethanolamine molecule.

Important Lipids

• Sphingomyelins are in the myelin sheaths of nerve cells and are associated with diseases such as multiple sclerosis.
• Johann Thudichum discovered sphingolipids in 1874 and named these brain lipids after a monster of Greek mythology, the sphinx. The sphingolipids appeared to Thudichum as part of a dangerous riddle of the brain.

Glycolipids

• Glycolipids are complex lipids that contain carbohydrates and ceramides.
• Cerebrosides consist of ceramide mono- or oligosaccharides.
• Gangliosides contain a more complex carbohydrate structure.
• In cerebrosides, the fatty acid may contain either 18-carbon or 24-carbon chains (the latter only in complex lipids).
• Glucose or galactose carbohydrate unit forms a β-1-glycosidic bond with the ceramide portion of the molecule.
• Cerebrosides occur primarily in the brain (accounting for 7% of the brain's dry weight) and at nerve synapses.

Steroids

• Steroids are the third major class of lipids, and are compounds containing the fused ring system.
• Three cyclohexane rings (A, B, and C) are connected to cyclopentane (D), and are different in structure from the lipids.
• May not be esters
• The most abundant steroid is cholesterol, serving as a plasma membrane component in all animal cells—for example, in red blood cells. Its second important function is to serve as a raw material for the synthesis of other steroids, such as the sex and adrenocorticoid hormones and bile salts. Cholesterol consists both in the free form and esterified with fatty acids, with gallstones consisting of free cholesterol.

Lipid storage diseases

• Classified by complex lipids being constantly break down and synthesized in the body.
• Genetic diseases exist in which some of the necessary enzymes to break down enzymes correctly, and often result in liver enlargement, mental retardation, blindness, and death.

Cholesterol

• High serum cholesterol levels have been correlated with diseases such as atherosclerosis and have received publicity.
• Instead, cholesterol is important for life.
• The amount of the liver manufactures satisfies needs, even without dietary intake.
• When the blood levels exceed 150 mg/100 mL, cholesterol synthesis in the liver is reduced to half the normal rate of production. Cholesterol is usually regulated, excess (not presence) is associated with disease. Excess cholesterol must be treated rather than limited. Only 10-15% comes from ingesting itself.

Lipoproteins

• Transport cholesterol along with fat
• Lipoproteins contain a core of hydrophobic molecules and are surrounded by a shell (hydrophilic; proteins and phospholipids)
• Four kinds -HDL (33% protein, 30% cholesterol, etc.) -LDL (25% protein, 50% cholesterol, etc.) -VLDL (mostly triglycerides) -Chylomicrons (carry dietary lipids)

LDL Transports

• VLDL is carried by the serum (55mm in diameter), and except for a protein called apoB-100, are removed of its components. This shrinks the diameter (22 nanometers) and only contaisn cholesteryl esters, increasing density and becoming LDL after removal. Remains for 2.5 days). LDL carries cholesterol and receptor molecules line specific surface areas. Then binds spe-cifically after apoB-100 and after becomes taken via endocytosis, break down, and liberate free cholesterol. This becomes a membrane or can cause the opposite result from the system.

Cholesterol Transports Cont.

• Michael Brown and Joseph Goldstein (University of Texas) shared the 1986 Nobel Prize in Physiology or Medicine.
• If the receptors are insufficient, cholesterol accumulates in the blood or the cell can use, and both genetics and diet control cholesterol.
• Free cholesterols convert in the serum from HDL are converted to cholesterol esters. Theses liver cells is for steroid hormones and bile acid synthesis. Differs from that of the cholesterol uptake.

Levels

• Because all lipids are insoluble in water, the blood serum may raise as deposit on the arteries inner surface. This could reduce flow and lead to heart attacks, dysfuction, etc.
• Most cholesterol is transported via Low-density lipoproteins.
• The serum cholesterol amount is controlled by synthesis in the liver.
• Low diets or statin drugs can reduce the amount and promote synthesis of lipoproteins for blockage.
• High levels of HDL and low LDL is what is desired for the bloodstream from High-density.

Membrane Functions

• Cell and brain processes are affected by atherosclerosis.
• However, removal of cell membrane also control cholesterol levels, and regulation and a high content of choleserol and glycolipids. In which the two transports of ABC and ABCG1 are removed, mutant mice have found to increase cells for immunity.
• This offers an attack strategy.

Hormones

• Cholesterol starts it off but all are linked based on water solubility.

Bile Salts

• Oxidation Products occur in the liver to eliminate and produce cholesterol. The end of allphatic chains oxidized, and forms an amide bond.
• The result makes Red Bull. One end of the polar to be powerful and able to bond and be dispersed in fine portions to result action.

Oral Contraception

• Prevents from a synthetic compound with birth control to control.

Prostaglandis and Thromboxanes/Leukotrienes

• Prostaglandins -Discovered for contractile properties -Synthesized by arachonic acid and ringed closed (carbons 2 to 18). Enzyme named COX for this production, forming other prostaglandins to lead and indicate blood pressure as relaxing the cells. -COX have to enzyme forms, COX-1 and COX-2, producing for physiological prostaglandin production for the contraction, inflammation, congestion, and blood pressure. -NSAIDS and aspirin inhibit COX enzymes to help such attacks.

• Thromboxanes -Derivatives also are ring structured in the same way.

• Leukotrienes -Act and mediate hormonal responses by an oxidative mechanism and can occur mainly in white cells to make long contractions (asthma).

• Both can cause inflammation/inhibits to take these.

• The last way to counteract is inhibit (antagonist like Zyflo).

• Omega - 3 Used for clotting aid by fats and bifurcations, and blood arteries, PDGF to be dead. They help for both atherosclerosis and platelets. Are found in fishes

Membrane Functions (Transport)

• There are various transport membrane capabilities which act as a boundary cell or container. Two operate from membranes from the other portion. . These function is catalysis, such as receptors for the protein binding. Important is are whether to expend the cell. In passive, transport for high concentratin. Active, against it

Passive (Transport 36)

Subdivided to two categories

• Simple diffusion - Moves directly with no interaction and across without changing to another and small portion
• Facilitated diffusion - Move molecule across with usage for carrier protein, etc.. By passively into the cells that contains.

Active (Transport 37)

• Requires move but against the gradients (solutes). Primary to gradients and energy, water is pumped with hydrolysis or ATP (sodium). and are connected.

Protein (Sodium Potas)

• ATP and water. One of the Subunit hydrolyzed and from is connected Interior Ions. Channel ions with conformational (phosphate subunit). Two bond cell pumps by allowing cell (4). Can be reversed and is similar. Both known there of a calcium Ion pump and transport Secondary Transports

Receptors

-Active with galacioside which don't hydrolysis from hydrogen gradients.

Interactions

-Membrane proteins for essential to each one and can be poisoned or by some protein. Receptors are difficult and based or membrane. Many or subunits.