notes lipids

7/30/2019 Notes Lipids

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Notes Lipids

Lipids are a group of molecules which include: fats, oils, waxes, phospholipids, steroids (likecholesterol), 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 andwaxes.

Before we discuss lipids we should review a specific carboxylic acid, the fatty acid and esters.The functional groups for each are shown below:

C

O

OHR C

O

OR R

carboxylic acid ester

The oxidation of a primary alcohol will lead through an aldehyde to a carboxylic acid.

[O]C CH

H

H H

H

OH C CH

H

H H

O

H[O]

C CH

H

H H

O

OH

primary alcohol aldehyde carboxylic acid

A fatty acid is simply a carboxylic acid in which the R group is very long. It consists of manycarbons chained together with hydrogens completing their octet.

HO C

O

C CH

H H

CH

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

CH

H

HH

H

palmitic acid - a fatty acid

To create an esteran alcohol combines with a carboxylic acid in a dehydration reaction, whichproduces the ester and a water molecule.


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C

O

CH3 OH

alcohol

CC H

H

HH

H

HO

carboxylic acid

CC H

H

HH

H

C

O

CH3 OH2O

ester

Again, the main purpose of fats and oil is to store energy. Hence if you eat more calories thanyour 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 lowfood supply. These days this seemingly good genetic trait has lost its usefulness. A persontrying to lose weight (fat) is fighting against millions of years of evolution. They are fightingagainst their own genes; the genes that allowed their ancestors to survive and eventually createthem. If you think about it, the battle of the bulge is really a battle against the survival of thestrong. Darwin would be so upset. Or maybe not, if we look at the genes being passed downwhat trend will be observed over the next millennia, thinner people. People with bodies moreadapted to a sedentary life.

Fatty acids come in two main classes, saturated and unsaturated. These classes are have thesame meaning as used in naming hydrocarbons. Saturated, like alkanes, indicates that thecarbon has as many hydrogens as possible bonded to said carbons, all single bonds, no doubleor triple. Unsaturated, like alkenes and alkynes, indicates that hydrogens could be added to thecarbon chain, for instance in an addition reaction across a double or triple bond. The palmiticacid shown above is a saturated fatty acid. Below is a picture of an unsaturated fatty acid:

HO C

O

C C

H

H H

C

H

C

H

H

C

H

H

C

H

H

H

H

C CH H

C C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

H

H

H

1 2 3 4 5 67

8 9

1011 12 13 14 15 16 17

As you can see the carbons have been numbered. It is important to know the location of thedouble 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 doublebond. Another aspect of the double bond is stereo chemistry. The above fatty acids doublebond is a cis isomer. As for naming the above fatty acid, it has one double bond on the 8thcarbon, 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 bythe media. The acids can be named for how far the double bond lays away from the final tailcarbon. Linolenic acid has a double bond, three carbons from the fatty acids end. It isclassified as an omega-3 fatty acid, the omega carbon being the terminal carbon and the bondbeing found on the third carbon from the end. Linoleic acid is an -6 fatty acid. Of all theunsaturated fatty acids the body utilizes these two are considered essential fatty acids, as thebody can not synthesize these. They must be consumed to fill the bodys needs. Linoleic andlinolenic acids are both polyunsaturated fatty acids, meaning they have more than one carbon-carbon double bond and they both contain 18 carbons.


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Fat, oil and wax are made from two kinds of molecules: glycerol (a type of alcohol with ahydroxyl group on each of its three carbons) and three fatty acids joined by esterification, adehydration reaction.

3 stearic acid molecules

C

O

HO

C

O

HO

C

O

HO

glycerol

CH2

CH OH

OH

CH2 OH

C

O

O

C

O

OCH

C

O

OCH2

CH2

triglyceride

The triglyceride molecule is the bodys storage molecule for fatty acids. The fatty acid, stearicacid, in the triglyceride above is the energy storage molecule used by steer. If you eat a steakthis is a molecule floating through your veins.Below you will find a triglyceride. But there is a major difference between the triglyceride belowand the one above. The double bond in the third fatty acid changes the structure of thismolecule. This causes the molecule to kink, and makes it turn. This keeps the molecule fromlaying 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 maindifference between an oil and a fat. The fats have more intermolecular forces being exertedbetween each other. This causes them to be a solid at room temperature.

Normal: Less than 150 mg/dLBorderline High: 150-199 mg/dLHigh: 200-499 mg/dLVery High: 500 mg/dL or above


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Why do fish have more polyunsaturated fatty acids than cattle? Fish are very concerned withthe loss of heat to water. The more loosely packed their lipids are the less likely heat willescape. 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 notas dense, they do not transmit heat well. The polyunsaturated lipids in fish are not denselypacked 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 notsoluble 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 cansee after a good violent shaking, the dressing looks to be mixed, but you have actually createdsomething called a micelle which is depicted below.


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As you can see from the picture all the hydrophobic tails have come together to talk about howscared they are of water. The hydrophilic end is actually so tightly pressed together they form awater tight seal. This is a VERY important molecule in the delivery of certain drugs. Not alldrugs are soluble in water, or can be made to be soluble. This gives the pharmaceuticalcompany 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 drugto 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 amaterial. The non-polar compound takes refuge in the micelle from its watery environment. Thehydrophobic areas find each other. When you rinse your clothing the dirty micelle is washedaway.

Soap is produced by reacting of a long chained fatty acid and a strong base. Normally an oiland 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.

+ NaOH

+ H2O

fatty acid + strong base soap + water

The first soaps were created by cooking animal fat with campfire ash. Animal fat is the source

of fatty acid and the wood ash is the strong base, potassium hydroxide, KOH.

Cell membranes are composed of lipids. The micelle is great but our cells are composed mostlyof water, those hydrophobic tails dont want to have water floating amongst them, so themembrane is composed mostly of a lipid arranged in a double layer with the tails from bothlayers inside (facing toward each other) and the heads facing out (toward the wateryenvironment) on both surfaces. The two drawings below show the lipid bi-layer:

C C C C C C C C C C C C C C C C

O

OHH

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

C C C C C C C C C C C C C C C C

O

NaH

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H


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These membrane lipids normally are phospholipids, which is a triglyceride with a phosphatesubstituting 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. Thephosphate 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 themolecule 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 reallyhappening is that the phosphate and its functional group are atop the two long fatty-acid chains.


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C O

O

CH2H2C

O

P

O

O O

C O

O

CH

R

An emulsifying agent is a substance which is soluble in both oil and water, thus enabling the twoto mix. A famous phospholipid is lecithin which is found in egg yolk and soybeans. Egg yolk ismostly water but has a lot of lipids, especially cholesterol, which are needed by the developingchick. 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.


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

sphingomyelin

fatty acid

CH3(CH2)12CH CH C H

OH

C

CH2O

HNHC

O P O

O

O

CH2CH2N(CH3

sphingosine

CH3(CH2)12CH CH C H

OH

C

CH2OH

HH2N

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 Americansare 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 areremoved, 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 wasfound that seminal fluid caused a uterus, that had undergone a hysterectomy, to contract. Theirname comes from the mistake of the scientist who isolated the compounds; Ulf von Euler, hadthought they were produced in the prostate gland. The prostoglandins are derived from theoxidation of arachidonic acid.

COOH

arachidonic acid

Prostoglandins are exceptionally powerful biological molecules. Not only are they powerful, butcontrol 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 andthen sustained, the inflammation will be retarded and the injury will heal more quickly andwith less pain. An analgesic can stop the oxidation of the released arachidonic acid in to theprostaglandins. 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. Theadministration of large doses of some prostoglandins during early pregnancy has been usedfor drug induced abortions. Prostoglandins have also been related to women who sufferfrom extremely painful menstruation cycles.

3. Dilation of the kidney renal blood vessels is controlled by prostaglandins. An increase intheir concentration will lead to greater electrolyte excretion.


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4. Gastrointestinal protection is another function of the versatile prostaglandin. They protectthe stomach by controlling the production of stomach acid and by covering its interior with amucus layer. As aspirin inhibits prostaglandin development, it has been shown thatexcessive 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 toclot 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 asthmaticattacks.


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Steroids:The general structure of cholesterol consists of two six-membered rings side-by-side andsharing one side in common, a third six-membered ring off the top corner of the right ring, and afive-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 thefunctional 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 fourrings that make up the central structure. As depicted below each ring is labeled and eachcarbon is numbered. Typically a hydroxyl group will be attached to the #3 carbon.

DC

BA2

3

4

5

10

1 9

8

7

6

14

13

12

1117

16

15

Cholesterol is not a "bad guy!" Our bodies make about 2 g of cholesterol per day, and thatmakes 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 theaction of UV light in sunlight on cholesterol molecules that have "risen" to near the surface of theskin. Our cell membranes contain a lot of cholesterol, in between the phospholipids, to helpkeep them fluid.

HO

cholesterol

Many people have heard the claims that egg yolk contains too much cholesterol, thus should notbe eaten. An interesting study was performed at Purdue University a number of years ago totest this theory. Men in one group each ate an egg a day, while men in another group were notallowed 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 experimentshowed no significant difference in blood cholesterol levels between egg-eaters and non-egg-eaters while there was a very significant difference between the men who got exercise andthose who didn't.

The problem with cholesterol is the same as most problems, too much. A typical American willconsume 400-500 mg of cholesterol a day. The AHA recommends a maximum of 300 mg. Thenumber one killer of men and women over the age of 50 is heart disease. This is brought on byelevated levels of cholesterol which will block arteries. When the blockage occurs in the blood


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vessels supplying the heart with blood, a heart attack is very likely. Also, excess cholesterollevels can exceed the saturation level in bile, causing gallstones to form. Gallstones are almostall cholesterol with a small amount of minerals, like calcium. Maximum cholesterol levels in theblood would be 220 mg/dl of blood plasma.

Bile is mentioned here as bile is another steroid. Bile salts are synthesized in your liver fromcholesterol. 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 sufferfrom jaundice and turn yellow. One other problem is these stones can cause extreme pain. Thetype of pain normally reserved for childbirth.

Hormones are another derivative of steroids. The word hormone is derived from the Greekword for arousal. At there essence hormones are chemical messengers. As you can seebelow, the structure of these molecules are very similar to that of cholesterol. Drawn below arefour different sex hormones. Testosterone and estrogen are well documented hormones whichgive males and females their unique physical characteristics. They also cause the production ofthe gametes. Progesterone prepares the uterus for a fertilized egg, if none arrives thenprogesterone begins the process of menstruation. Norethindrone is a synthetic hormone used

as a contraceptive.

O

OH OH

HO O

C O

O

OHC CH

testosterone - androgen

estradoil - estrogen

progesterone

norethindrone

From what your have read above, steroids are essential to life. But the word steroid carries anegative connotation. The anabolic steroids used to increase physical performance can causeterrible long term damage to the liver and actually cause male to become infertile. Side effectsduring 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 andstanozolol. Nandrolone is shown below, notes its similarity to testosterones structure. The twomolecules vary only by the methyl group from the #10 carbon.

O

OH

Nandrolone


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Lipoproteins are clusters of proteins and lipids all tangled up together. These act as a meansof carrying lipids, including cholesterol, around in our blood. There are two main categories oflipoproteins distinguished by how compact/dense they are. LDL or low density lipoprotein is thebad 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 cholesterolout 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 consideredthe most damaging. It is most likely to deposit its cholesterol in arteries forming atheroma. Anatheroma is an abnormal inflammatory accumulation of macrophage white blood cells within thewalls of arteries. These can be thought of as anatomic lesions. The atheroma are proteins thatspecialize in storing fat. So, if a VLDL is going to give up its cholesterol, the atheroma is a placethe deposit can occur.

Many important molecules in the body are lipids. But transporting these molecules around thebody through the blood presents an obvious problem, because, by definition, lipids are nonpolarand thus not very soluble in water. Small amounts of fatty acids are transported in the bloodbound 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 severalthousand molecules. These particles solve the problem of lipid/water incompatibility via theamphipathic nature of phospholipids. One end of these molecules is polar and the other endnonpolar.

Lipoproteins have a single layer of phospholipid molecules on their outside, surrounding acentral core. (By contrast, plasma membranes are comprised of a BILAYER.) Since the polarpart of each phospholipid faces out, the outside of the phospholipid molecule is polar and thuscompatible 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 thecore of the lipoprotein.

As shown in the figure, the outer layer of the lipoprotein also has a protein molecule called anapolipoprotein. Like phospholipids, this protein is also amphipathic and helps stabilize theparticle. But even more important, the protein serves to identify the specific lipoprotein. Forexample, some lipoproteins transport dietary lipids from the small intestine to adipocytes and theliver. Other lipoproteins transport cholesterol between different parts of the body. Each type oflipoprotein can be identified because it has a different apolipoprotein.


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

notes lipids

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