Download I Revised - UAB School of Optometry

Fundamentals I
Lipids
9/9/08 10-11am
Whikehart
Lipids (*revised with jokes and stuff*)
Please calibrate your clickers for the day. We won't start that right away but during this
lecture I will. We have some visitors that will be a little late, but that is alright I will get
started anyway. The average for the exam yesterday was overall an 84 which is very
good. I will post the results in the optometry and dental school. I was very pleased with
the way it worked out and I hope that you all will continue the good work.
Joke
There were 3 passengers in a plane that was about to crash. One individual one was the
smartest man in the world, one was the president, and one was a little girl. There were
only two parachutes. The smartest man said I am the smartest man in the world and
others would benefit by my survival and he grabbed a parachute and jumped out. The
President said I have lived a long life and you are just starting yours, to the little girl of
course. You go ahead and take the last parachute. The girl said, Don't worry there is one
for both of us because the smartest man in the world just took my backpack.
The subject today is lipids and it has hardly been covered before.
Slide #1- Lipids
If you watch TV...
 It is almost impossible to watch TV ads without some company talking about fats and
dieting. We’re familiar with that, but we still crave the foods that contain fats and still
know very little about them.
Slide #2- What are we going to be covering today?
 Fatty acids which are lipid building blocks
 Triacylglycerides and Phospholipids
 Sphinomyelins- alot of people in biochemistry consider this a difficult subject, but if I
break it down it is not very difficult.
 Cholesterol and Friends (Steriods)
Slide #3- Essential Information
 Fats are lipids, but NOT ALL LIPIDS ARE FATS. Both substances are soluble in
non-polar solvents -- like benzene and xylene (liquids used in organic chemistry).
However, the terms lipids and fats have different meanings even though they are both
soluble in these non polar solvents.
 Fats are esters formed from fatty acids and the compound glycerol. Animals use fats
for energy storage and insulation. (More information will be given later)
 Lipids are compounds soluble in a non-polar solvents, but they don’t have to be esters
 Remember the previous definition: Fats are esters made out of fatty acids and the
compound glycerol.
Slide #4
 So a lipid could include stuff like gasoline or jet engine fuel (specially formulated
kerosene)
 Or even be in that material in our bodies that the weight reduction people call
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“cellulite”- tissue composed of cells full of triacylglerols, which is a type of fat
 We have to be careful how the terms are used. All the compounds used in this course
are all accurately called lipids.
Slide #5- Some Examples of Lipids
 Top left hand side- Cholesterol- it has gotten a bad name over the years but you can
not live without it
 Bottom left hand side- Warfarin (Coumadin)- blood thinner. Also used as a poison to
kill rodents. If the rodent ingests it he will die because he bleeds out- you may
consider it a little harsh but it is used quite commonly as a rodent killer.
 Right- Tristearin- this is a fat.- triacylglycerol or triglyceride- has 3 long tail like
structures that are part of a fatty acid and on the top is a glycerol molecule
Slide #6- Why are lipids important?
1. They are a significant source of fuel/ energy.- Lipids are more of a source of energy
than proteins or carbohydrates.
2. They form borders for cells and within cells
3. They are sources of hormones & vitamins.
Slide #7- Some Examples
 Triacylglycerols- (fats)
-Important fuel for heart tissue- about the only fuel for heart tissue
-Under starvation they can nourish other tissues particularly in diabetes- insulin
dependent tissues no longer to absorb carbohydrates; use triacylglycerides as a fuel
substitute; however causes problems after awhile.
 Phospholids and Cholesterol-Form and maintain plasma membranes
-Sub-cellular organelle boundaries
-Cholesterol itself which is used as a precursor for many types of hormones.
Slide #8- Lipid Solubility Characteristics
 He said he spent some time looking over this because he had never had it explained
satisfactorily as a student.
 It goes without saying that lipids are soluble in non-polar solvents. Yeah it is a
given... That is, there is no partial charge in any part of a lipid solvent such as is
found in water. Dr. Miller has talked about this before.
 Refer to picture: In water, the oxygen molecule is electron withdrawing, it tends to
pull electrons away from the hydrogen. The hydrogen atoms attain a positive charge
and the oxygen a negative charge- Polarity
 Energetically, Lipids are stable in non-polar solvents and are called hydrophobicwater hating compounds


Of course, there are exceptions. Some lipids have a portion of their composition that is
compatible with water. For example: Fatty acid- one end of the molecule has a carboxyl
group partially ionized (charged), rest of molecule has no charge.
Fatty acid with long chain- not very soluble in water- solubility decreases
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


Short chain fatty acids- very soluble in water. Example vinegar- 5% acetic acid, completely
soluble
Most lipids are not very soluble in water, problems with solubility
amphipathic- dual roles- polar end and non-polar end
Slide #9- What exactly is a hydrophobic bond?
 It is not a true bond, but an association of non-polar compounds made to minimize
their contact with a polar solvent (usually water). This is energetically favorable for
the polar solvent.
 It helps if the non-polar compound (such as a lipid) has some hydrophilic region(s).
 See diagram- Series of fatty acids in water... What happens? non polar ends start to
associate in a structure called a micelle
 The micelle structure is composed of fatty acids in which
a) the alkyl groups are buried inward
b) the carboxyl groups (charged) interact with
the polar water molecules.-face outward
 What if there are no hydrophilic regions?
Suppose you had a lipid that was dumped into a pool of water or a beaker of water.
Suppose that oil dropped out of a car and it was raining outside and you had water
underneath that... What would occur? Contact between lipid and water would become
minimized. Take a separatory funnel and you have water or a water soluble compound
and lipid and shake it, you get a phase separation- you have minimal contact between the
water molecules and the lipid itself. Energetically favorable for the polar solvent.
Slide #10 Non-polar solvents- Heptane and cyclohexane- no region in these molecules with any
polarity
 Partially polar lipids- palmetic acid and oleic acid -region of non-polarity is the alkyl
groups and the carboxylic acid groups
Slide #11- Fatty acids: lipid building blocks
 Fatty acids are lipid building blocks of most lipids even cholesterol (fatty acids will
for esters with the cholesterol itself)
 Fatty acids have two parts: a hydrocarbon tail and a carboxylic head
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COO- H+
 Fatty acid above: DODECANOIC ACID (systematic name or name applied by the
International Union of Pure and Applied Chemistry) or LAURIC ACID(common
name- source from where first observed)
 Greek = 12 (dodekanos = dodekanos)
 Latin = laurel plant (laurus)
Slide #12
 Examples of names:
 Saturated fatty acid- Palmitic acid and Stearic acid
 Can take fatty acids and remove hydrogens and get double bonds
 Monosaturated- one double bond- Oleic acid
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 Diunsaturated- 2 double bonds- Linoleic acid
 Polyunsaturated- 3 or more double bonds- alpha-Linolenic acid (3) and Arachidonic
acid (4) (Arachinoid- spider- where acid name comes from)
Slide #13- Fatty acid facts
 FA have both IUPAC (systematic) & common names.



FA partially deionize.- why some can be used as buffers
Most biological FA are usually 12-24 carbons long- but can get up to about 36
FA are either completely saturated or have one or more double bonds.
 carbon length -  melting point
 unsaturation -  melting point
Slide #14
 Some examples- see graph- go from 9 C to 24C then see melting point increases in
an increasing curve.
 Important for cell membranes- if you increase the degree of unsaturation (number of
double bonds) in fatty acids, you decrease the melting point, you increase randomness
or disorder of a fatty acid in a membrane; thus, making it more fluid.
 Cell membranes will be a mixture of degrees of saturation and unsaturation.
Slide #15- Some Shorthand Naming
 Short-hand methods for naming FA begin with either the carboxylic acid end(
biochemists) or the methyl end of the molecule( nutritionists):
 lauric acid = 12:0; oleic acid = 18:1
 linolenic acid = 18:3 D9,12,15 (This is also an w-3 fatty acid)
18:3 indicates an 18C fatty acid with three double bonds;
D9,12,15 shows the positions of the double bonds; and w-3 states the double bond begins
at C3 from the methyl group (opposite of the carboxyl group)
Slide #16
 Look at linolenic acid- an omega 3 fatty acid. At 3 position is the first double bond.
Slide #17
 Two configurations: cis (groups on same side of double bond) and trans (opposite
sides)
 Commercial hydrogenation ( process of adding hydrogen to a fatty acid which is
unsaturated) converts FA in the cis configuration (shown on the left) into saturated FA.
However, side reactions produce trans FA (shown on the right). Trans FA increase LDLlow density lipoprotein (containing so called “bad” cholesterol) -lipids in the body that
cause a buildup of arterial lipid deposits leading to atherosclerosis.
Slide #18- Saturated vs. Unsaturated FA
 See table from textbook
 There is a wide variety of FA consumed in our diets and it depends on the source of
the lipids.
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 Saturated FA- high in beef
 Whole milk- high palmitic and stearic acid
 Amount of unsaturated acids higher in corn oil.
 Want to have more unsaturated than saturated fat in diet.
Slide #19
 There are two issues, then, concerning the consumption of FA in the diet:
1.
excessive intake of saturated FA (beef and butter as examples)
2.
excessive intake of trans-FA (margarine made by hydrogenation)
 Some oils that tend to be low in saturated and trans-FA are canola, olive and flax
seed.
Slide #20- Analysis of Fatty Acids:
 Know this!- not in textbook
1. Take given tissue (example is a piece of liver) and homogenize in
chloroform/methanol/H2O.
2. Put extract in separatory funnel and get two separate phases.
3. Analyze each phase by either:
a. absorbtion chromotography- silicic acid in solvent
b. thin layer plate which contains silicic acid, and after you run a solvent and get
separation of different types of lipids.
 How do you get FA after you have made the separation? Treat (b) or (c) NaOH and
methanol to produce fatty acyl methyl esters (transesterfication). Purpose: to make
fatty acid derivatives that are easily volitized- can be converted into gas.
 Put on high performance liquid chromatography or a gas liquid chromatograph
converting these to gases.
 Gases will go through a series of coils and separate out. When get to the end of coil,
burned at a hydrogen flame which will send a signal to an apparatus which will print
out and get shorter chain at bottom and longer chains that have unsaturated
 Can tell what is there and the quantity. This is a way to analyze fatty acids.
Slide #21- Stored Fat: Triacylglycerols (TGs)
 adipocytes- fat cells in body- see picture
 When consume lipids gastrointestinal system will convert them and break them down
to fatty acids, and transported to fat cells where they will be assembled into a TG
 Reaction occurs by acyl transferase; 3steps- each step puts one FA onto glycerol
molecule.
 Glycerol comes from glucose and is a biproduct in the EM pathway.
 TGs stored in small lipid bodies within the adipocyes.
Slide #22- TG Facts
 Most of the FAs in TGs are of mixed chain length and degree of saturation (important
for membrane properties).
 The energy obtained by metabolic oxidation of TGs is ~2.2x that of proteins and
carbohydrates. Under starvation, lipids are the main thing broken down.
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 TGs are an important temperature insulator for animals.
Slide #23- Saponification (Fat Hydrolysis)
 Artificially: Treat TG with KOH or NaOH then heat and get glycerol and potassium
or sodium salt (Soap). Old days: ash and animal fat- soap
 Cells produce their own form of TG hydrolysis by using lipase enzymes to separate
FAs prior to transporting them and combining them into new lipids.
 Lipids constantly being broken down or separated from their parent compound, being
put into fat cells and transported to some location in body where they are needed to
make membranes.
Slide #24- Structural Forms of Lipids
There are three types of lipids that are used to form tissue structures (membranes):
•
Glycerophospholipids (not TGs)
•
Sphingolipids
•
Steroids (Cholesterol)
Slide #25- Glycerophospholipids
 Glycerophospholipids (phospholipids) are a variation of TGs, but they substitute a
polar headgroup for one of the FA parts.
 See phosphatidic acid picture- parent compound of what you see in cells- phosphate
group and two FA's esterified to the glycerol molecule
 glycerol molecule is a hinge molecule
Slide #26- Types and Nature of Head Groups:
 Choline
 Ethanol amine
 Serine (an AA)
 Phosphoglycerol
 Diglycerol phosphate (Cardiolypin)
 Phosphtidylinositol (derivative of glucose)
 Polar head groups are unique.
 Inosine is a derivative of glucose.
 Each head group has some degree of polarity.
Slide #27
 Glycerophospholipids are glycerol units to which are esterified: 2 Fatty acid and one
polar head unit.
 The fatty acids are commonly mixed- one unsaturated and one saturated (usually)
 The head units consist of 6 common types- choline and ethanolamine are two of the
most common types.
 Glycerol is a hinge molecule.
Slide #28
 Glycerophospholipids (PL) for most of us serve as membrane components primarily
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and as fuel secondarily.
 The polar bear uses PL as:
1)
An insulator- gathers alot of fat
2)
A fuel- only eats 4 months of the year, got to have something else
3)
A source of H2O(cant drink snow or ice and water is too cold, so can't drink):
PL  PHG + FA  FA (- 2C)  HOH
 Takes the PL and breaks it down into phospholipid and polar head group. Then it
takes the fatty acid and uses it to push through TCA cycle. Then onto oxidative
phosphorylation, where biproduct is H2O.
 Very efficient
Slide #29- Sphingolipids
THE RIDDLE OF THE SPHINX:
What goes on four feet in the morning;
Two feet in the afternoon; and
Three feet in the evening?
 See man, bird, lion which guarded the city of Theives; if a person wanted to get into
town they had to answer this riddle. If they did not answer it correctly, then they
were strangled. This is a very twisted and convoluted story. Lions will kill prey by
strangulation. Story is Egyptian in origin, but this is the Greek version. There are
also oriental versions. How do we get sphingolipids from all this?
Sphingolipids- a class of lipids whose structure perplexed investigators
Slide #30
 Sphingolipids use sphingosine as their hinge molecule instead of glycerol.
 See sphingosine molecule
 Hybrid molecule
 Glycerol in the center
 On C2 there is an amino group instead of a hydroxy group
 One end is the remains of a fatty acid held together in a double bond that is now an
ester bond.
Slide #31- Examples of Sphingolipids
 Ceramide-bound to a FA through an amide bond on C2- wax compound
 Cerebroside- add 1 sugar or carbohydrate group
 Sphingomyelin- bound to a choline group
 Gangliside- 2 or more sugar or carbohydrate groups
 Cerebroside and Gangliside are isolated from nervous tissue, and some from muscle
tissue.
Slide #32
1. Are often found in nervous membranes of higher animals.
2. Sphingomyelin is also found in muscle membranes.
3. Glycosphingolipids are also immunomarkers for cells-investigators found these in non
nervous and non muscle tissue... the reason was that these sugar molecules extend out
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from membrane to identify cells as “friend or foe“.
Slide #33- A Note to Consider
 The degredation of gangliosides occurs in lysoomes and is an important process. If a
defieiency in one or more degradative enzymes occurs there, then a disease known as
a metabolic storage disease may occur.
 An example is Tay-Sach’s Disease in which a ganglioside is only partially degraded
due to the deficiency of the enzyme: hexosaminidase A. The excess lipid causes
mental retardation and eventually death.
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