Notes Lipids

Lipids are a group of molecules which include: fats, oils, waxes, phospholipids, steroids (like cholesterol), sphingolipids, and prostaglandins. The main purpose of lipids is to store energy. Other very important functions include: o padding for organ o dissolving fat soluble vitamins o steroids used in messaging, decomposition of large molecules, hormones.. o transportation of some molecules through the blood o cell membrane structure

These molecules perform different functions in an organism. We will begin with fats, oils and waxes. Before we discuss lipids we should review a specific carboxylic acid, the fatty acid and esters. The functional groups for each are shown below: O R C OH carboxylic acid O R C O R ester

The oxidation of a primary alcohol will lead through an aldehyde to a carboxylic acid. H H H C C H H primary alcohol OH [O] H O H C C H H H aldehyde [O] H O H C C H H carboxylic acid OH

A fatty acid is simply a carboxylic acid in which the R group is very long. It consists of many carbons chained together with hydrogens completing their octet. O H H H H H H H H H H H H H H H HO C C C C C C C C C C C C C C C C H H H H H H H H H H H H H H H H palmitic acid - a fatty acid To create an ester an alcohol combines with a carboxylic acid in a dehydration reaction, which produces the ester and a water molecule.

O CH3 C OH

H H HO C C H H H alcohol CH3

O C O

H H C C H H H ester

H2O

carboxylic acid

Again, the main purpose of fats and oil is to store energy. Hence if you eat more calories than your body needs, you turn these extra calories into fat for storage. This is a very basic need; the more fat an organism can generate the more likely that organism will survive in times of low food supply. These days this seemingly good genetic trait has lost its usefulness. A person trying to lose weight (fat) is fighting against millions of years of evolution. They are fighting against their own genes; the genes that allowed their ancestors to survive and eventually create them. If you think about it, the battle of the bulge is really a battle against the survival of the strong. Darwin would be so upset. Or maybe not, if we look at the genes being passed down what trend will be observed over the next millennia, thinner people. People with bodies more adapted to a sedentary life. Fatty acids come in two main classes, saturated and unsaturated. These classes are have the same meaning as used in naming hydrocarbons. Saturated, like alkanes, indicates that the carbon has as many hydrogens as possible bonded to said carbons, all single bonds, no double or triple. Unsaturated, like alkenes and alkynes, indicates that hydrogens could be added to the carbon chain, for instance in an addition reaction across a double or triple bond. The palmitic acid shown above is a saturated fatty acid. Below is a picture of an unsaturated fatty acid: O H H H H H H HO C C C C 4 C 5 C C 7
1 2 3 6

H H H H H H H H
10C 11

C C 13 C 14C 15C 16C C 17H

H H H H H H H

C C

H H H H H H H H H

As you can see the carbons have been numbered. It is important to know the location of the double bond as the use of the fatty acid will vary depending on the location of this double bond. Further more the nutritional value of the fatty acid is dependant on the location of the double bond. Another aspect of the double bond is stereo chemistry. The above fatty acids double bond is a cis isomer. As for naming the above fatty acid, it has one double bond on the 8 th carbon, is composed of 17 carbons and is cis, cis-8-heptadecanoic acid is its name. Common names have been also developed; certain fatty acid names have been popularized by the media. The acids can be named for how far the double bond lays away from the final tail carbon. Linolenic acid has a double bond, three carbons from the fatty acids end. It is classified as an omega-3 fatty acid, the omega carbon being the terminal carbon and the bond being found on the third carbon from the end. Linoleic acid is an -6 fatty acid. Of all the unsaturated fatty acids the body utilizes these two are considered essential fatty acids, as the body can not synthesize these. They must be consumed to fill the bodys needs. Linoleic and linolenic acids are both polyunsaturated fatty acids, meaning they have more than one carboncarbon double bond and they both contain 18 carbons.

Fat, oil and wax are made from two kinds of molecules: glycerol (a type of alcohol with a hydroxyl group on each of its three carbons) and three fatty acids joined by esterification, a dehydration reaction. O HO C CH2 CH CH2 OH OH OH O HO C O HO C 3 stearic acid molecules O CH2 O C O CH O C O CH2 O C triglyceride The triglyceride molecule is the bodys storage molecule for fatty acids. The fatty acid, stearic acid, in the triglyceride above is the energy storage molecule used by steer. If you eat a steak this is a molecule floating through your veins. Below you will find a triglyceride. But there is a major difference between the triglyceride below and the one above. The double bond in the third fatty acid changes the structure of this molecule. This causes the molecule to kink, and makes it turn. This keeps the molecule from laying on a neighboring molecule closely. The molecules simply can not pack as close together. This keeps the molecules from being able to form bonds with each other. This is the main difference between an oil and a fat. The fats have more intermolecular forces being exerted between each other. This causes them to be a solid at room temperature. Normal: Less than 150 mg/dL Borderline High: 150-199 mg/dL High: 200-499 mg/dL Very High: 500 mg/dL or above

glycerol

Why do fish have more polyunsaturated fatty acids than cattle? Fish are very concerned with the loss of heat to water. The more loosely packed their lipids are the less likely heat will escape. Think about metals, they are dense, molecules are close together, and they conduct heat very well. How about plastic, their molecules are not as close to each other, they are not as dense, they do not transmit heat well. The polyunsaturated lipids in fish are not densely packed and therefore dont allow heat to be released as easily as stearic acid, a saturated fat. If we look closely at the lipid, there are two distinct areas; a polar end and a non-polar tail. Since the tail is the major portion of the molecule, lipids are non-polar, hence they are not soluble in water. The polar end is hydrophilic, water loving and the non-polar tail is hydrophobic, water fearing. This is why your favorite Italian dressing must be shaken violently before using. The oil, normally olive, needs to be mixed with the vinegar, which is mostly water. As you can see after a good violent shaking, the dressing looks to be mixed, but you have actually created something called a micelle which is depicted below.

As you can see from the picture all the hydrophobic tails have come together to talk about how scared they are of water. The hydrophilic end is actually so tightly pressed together they form a water tight seal. This is a VERY important molecule in the delivery of certain drugs. Not all drugs are soluble in water, or can be made to be soluble. This gives the pharmaceutical company a vehicle to deliver any medication that is non-polar. You may ask what is the problem with delivery. Well, water is the major constituent of the bloodstream, water is polar. So, if you want to distribute non-polar drug throughout the body you need a way to get the drug to dissolve in the bloods water. The micelle facilitates this transfer. Soaps work by forming micelles which interact with non-polar compounds on the surface of a material. The non-polar compound takes refuge in the micelle from its watery environment. The hydrophobic areas find each other. When you rinse your clothing the dirty micelle is washed away. Soap is produced by reacting of a long chained fatty acid and a strong base. Normally an oil and lye are mixed together and heated. The result is an alcohol, which evaporated while you are cooking the mixture and a long chained fat with a sodium ion replacing the acidic hydrogen.
H H C H H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H H C H O C Na O C OH

+ NaOH + H 2O

fatty acid + strong base soap + water

These membrane lipids normally are phospholipids, which is a triglyceride with a phosphate substituting for one of the fatty acids. Depicted below:

lecithin (pronounced "less-a-thin") Phospholipids are made from glycerol, two fatty acids, and a phosphate group. The phosphate group is attached to the glycerol but has another molecule attached to its other end. The hydrocarbon tails of the fatty acids are still hydrophobic, but the phosphate group end of the molecule is hydrophilic because of the oxygens with all of their pairs of unshared electrons. This means that phospholipids are soluble in both water and oil. The general form of a phospholipid depicts a polar head with two long tails. What is really happening is that the phosphate and its functional group are atop the two long fatty-acid chains.

R O O P O O H2C CH O C O CH 2 O C O

An emulsifying agent is a substance which is soluble in both oil and water, thus enabling the two to mix. A famous phospholipid is lecithin which is found in egg yolk and soybeans. Egg yolk is mostly water but has a lot of lipids, especially cholesterol, which are needed by the developing chick. Lecithin is used to emulsify the lipids and hold them in the water as an emulsion. Lecithin (pronounced "less-a-thin") is the basis of the classic emulsion known as mayonnaise.

Sphingolipids are the coating for nerve axons, myelin. The sphingolipid is not a derivative of glycerol. The structure of the sphingosine is drawn below. Once a fatty acid and a phosphate with an attached choline have bonded to the sphingosine, the sphingomyelin is created.

OH CH3(CH2)12CH CH C H H2N C H CH2OH sphingosine fatty acid

OH CH3(CH2)12CH CH C H C NH C H O O CH2O P O CH2CH2N(CH3)3

O sphingomyelin Without a proper myelin cover the nerves function erratically or stop functioning all together. The most notable disease of myelin is MS, multiple sclerosis. A quarter of a million Americans are afflicted with this disease. This is caused by a loss of myelin sheath which coats the nerves. When this occurs it has the same effect as shorting out your toaster; the wires become crossed. Since nerves are really electrical/chemical transmitters, if the cover on adjacent nerves are removed, the signals leak to the neighboring nerves creating a confusing signal which the muscles can not understand.
Prostaglandins are a group of fatty acid like compounds discovered in the 1930s when it was found that seminal fluid caused a uterus, that had undergone a hysterectomy, to contract. Their name comes from the mistake of the scientist who isolated the compounds; Ulf von Euler, had thought they were produced in the prostate gland. The prostoglandins are derived from the oxidation of arachidonic acid. COOH arachidonic acid Prostoglandins are exceptionally powerful biological molecules. Not only are they powerful, but control a wide variety of biological functions. These include: 1. The inflammation of injured tissue is instigated when the arachidonic acid is released from injured cells and are quickly turned into prostaglandins. If the area is cooled quickly and then sustained, the inflammation will be retarded and the injury will heal more quickly and with less pain. An analgesic can stop the oxidation of the released arachidonic acid in to the prostaglandins. Aspirin and ibuprofen are the most predominate analgesics on the market. Another inflammation problem that prostaglandins are found to be responsible for, is asthma. They can cause inflammation of the bronchial passageways causing restriction in air flow. These attacks may be brought on by any number of stimuli including allergies, stress or over activity. 2. The discovery of prostaglandins demonstrated another use, uterine contractions. An increase in prostoglandins in the uterus is seen just before the beginning of labor. The administration of large doses of some prostoglandins during early pregnancy has been used for drug induced abortions. Prostoglandins have also been related to women who suffer from extremely painful menstruation cycles. 3. Dilation of the kidney renal blood vessels is controlled by prostaglandins. An increase in their concentration will lead to greater electrolyte excretion.

4. Gastrointestinal protection is another function of the versatile prostaglandin. They protect the stomach by controlling the production of stomach acid and by covering its interior with a mucus layer. As aspirin inhibits prostaglandin development, it has been shown that excessive use of aspirin can lead to stomach ulcers. 5. A prostaglandin derivative compound thromboxanes is responsible for platelet aggregation. When a blood vessel is compromised thromboxanes are released causing the platelets to clot the leak. Blood thinning medication, such as aspirin will reduce the ability of platelets to come together and can cause excessive bleeding, especially during surgery. 6. Another prostaglandin derivative compound Leukotrienes are mainly found in white blood cells. They can produce long lasting muscle contractions which can cause asthmatic attacks.

Steroids: The general structure of cholesterol consists of two six-membered rings side-by-side and sharing one side in common, a third six-membered ring off the top corner of the right ring, and a five-membered ring attached to the right side of that. The central core of this molecule, consisting of four fused rings, is shared by all steroids. Examples of steroids include estrogen, progesterone, cortisone, aldosterone, testosterone, and Vitamin D. Steroids differ in the functional groups that are attached to the rings edges. Each of the examples listed above has the same central ring, but vary in their functional group. You should be able to draw the four rings that make up the central structure. As depicted below each ring is labeled and each carbon is numbered. Typically a hydroxyl group will be attached to the #3 carbon.
12 11 1 2 3 10 9 13 17

C
8 7

14

D
15

16

A
4

B
6

Cholesterol is not a "bad guy!" Our bodies make about 2 g of cholesterol per day, and that makes up about 85% of blood cholesterol, while only about 15% comes from dietary sources. Cholesterol is the precursor to our sex hormones and Vitamin D. Vitamin D is formed by the action of UV light in sunlight on cholesterol molecules that have "risen" to near the surface of the skin. Our cell membranes contain a lot of cholesterol, in between the phospholipids, to help keep them fluid.

HO cholesterol Many people have heard the claims that egg yolk contains too much cholesterol, thus should not be eaten. An interesting study was performed at Purdue University a number of years ago to test this theory. Men in one group each ate an egg a day, while men in another group were not allowed to eat eggs. Each of these groups was further subdivided such that half the men got "lots" of exercise while the other half were "couch potatoes." The results of this experiment showed no significant difference in blood cholesterol levels between egg-eaters and non-eggeaters while there was a very significant difference between the men who got exercise and those who didn't. The problem with cholesterol is the same as most problems, too much. A typical American will consume 400-500 mg of cholesterol a day. The AHA recommends a maximum of 300 mg. The number one killer of men and women over the age of 50 is heart disease. This is brought on by elevated levels of cholesterol which will block arteries. When the blockage occurs in the blood

vessels supplying the heart with blood, a heart attack is very likely. Also, excess cholesterol levels can exceed the saturation level in bile, causing gallstones to form. Gallstones are almost all cholesterol with a small amount of minerals, like calcium. Maximum cholesterol levels in the blood would be 220 mg/dl of blood plasma. Bile is mentioned here as bile is another steroid. Bile salts are synthesized in your liver from cholesterol. Bile salts assist in the digestion of lipids and other non-soluble molecules. If a gallstone is large enough it may block the channel used to release bile and the person will suffer from jaundice and turn yellow. One other problem is these stones can cause extreme pain. The type of pain normally reserved for childbirth. Hormones are another derivative of steroids. The word hormone is derived from the Greek word for arousal. At there essence hormones are chemical messengers. As you can see below, the structure of these molecules are very similar to that of cholesterol. Drawn below are four different sex hormones. Testosterone and estrogen are well documented hormones which give males and females their unique physical characteristics. They also cause the production of the gametes. Progesterone prepares the uterus for a fertilized egg, if none arrives then progesterone begins the process of menstruation. Norethindrone is a synthetic hormone used as a contraceptive.
testosterone - androgen OH progesterone OH OH C CH

C O

HO estradoil - estrogen

O norethindrone

From what your have read above, steroids are essential to life. But the word steroid carries a negative connotation. The anabolic steroids used to increase physical performance can cause terrible long term damage to the liver and actually cause male to become infertile. Side effects during use may include: hypertension, fluid retention, increase hair growth, sleep deprivation, acne and severe mood swings. A few anabolic steroids used include: methandienone, oxandrolone, nanodrolone and stanozolol. Nandrolone is shown below, notes its similarity to testosterones structure. The two molecules vary only by the methyl group from the #10 carbon. OH

O Nandrolone

Lipoproteins are clusters of proteins and lipids all tangled up together. These act as a means of carrying lipids, including cholesterol, around in our blood. There are two main categories of lipoproteins distinguished by how compact/dense they are. LDL or low density lipoprotein is the bad guy, being associated with deposition of cholesterol on the walls of someones arteries. HDL or high density lipoprotein is the good guy, being associated with carrying cholesterol out of the blood system, and is more dense/more compact than LDL. Another type is the VLDL, which is very low density lipoprotein. This lipoprotein is considered the most damaging. It is most likely to deposit its cholesterol in arteries forming atheroma. An atheroma is an abnormal inflammatory accumulation of macrophage white blood cells within the walls of arteries. These can be thought of as anatomic lesions. The atheroma are proteins that specialize in storing fat. So, if a VLDL is going to give up its cholesterol, the atheroma is a place the deposit can occur. Many important molecules in the body are lipids. But transporting these molecules around the body through the blood presents an obvious problem, because, by definition, lipids are nonpolar and thus not very soluble in water. Small amounts of fatty acids are transported in the blood bound to blood proteins. These are called free fatty acids (despite the binding). Beyond this, however, other lipids are transported in these specialized particles called lipoproteins. To emphasize, lipoproteins are not molecules, but rather particles comprised of several thousand molecules. These particles solve the problem of lipid/water incompatibility via the amphipathic nature of phospholipids. One end of these molecules is polar and the other end nonpolar. Lipoproteins have a single layer of phospholipid molecules on their outside, surrounding a central core. (By contrast, plasma membranes are comprised of a BILAYER.) Since the polar part of each phospholipid faces out, the outside of the phospholipid molecule is polar and thus compatible with the surrounding water environment. On the other hand, the nonpolar portion of each phospholipid faces inward, and thus is compatible with the very nonpolar ingredients of the core of the lipoprotein. As shown in the figure, the outer layer of the lipoprotein also has a protein molecule called an apolipoprotein. Like phospholipids, this protein is also amphipathic and helps stabilize the particle. But even more important, the protein serves to identify the specific lipoprotein. For example, some lipoproteins transport dietary lipids from the small intestine to adipocytes and the liver. Other lipoproteins transport cholesterol between different parts of the body. Each type of lipoprotein can be identified because it has a different apolipoprotein.

At the target cell, in some cases, the apolipoprotein binds to a receptor and then the lipoprotein is then taken up by receptor-mediated endocytosis. In other cases, an enzyme on the capillary wall, termed lipoprotein lipase, unloads transported lipids from the lipoprotein by breaking the monolayer membrane into fatty acids and glycerol through a desterfication reaction.