Lipids Lectures

for
CHY3007
Biochemistry

• Please note that all slides are subject to revision at the instructor’s
discretion and this document may not reflect those changes.

• It is the student’s responsibility to attend lectures and not to rely

entirely on these lecture notes.

• These slides are not a substitute for reading the book

Lipid: A substance of biological origin that is soluble in nonpolar solvents.
Lipids can be categorized as hydrolyzable and nonhydrolyzable.
[1] Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis
with water. Many hydrolyzable lipids contain an ester unit.

[2] Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous

hydrolysis.
 Intermolecular Forces
• Classes of Forces • Forces Affect
– Ion-Ion – Solubility
– Ion-Dipole – Boiling Point
– Hydrogen Bonds – Melting Point
– Dipole-Dipole
– Dipole-Dispersion
– London Dispersion
Forces
Physical Properties—Solubility
• The nonpolar part of a molecule that is not attracted to H2O is said to be
hydrophobic (a.k.a. lipophilic).
• The polar part of a molecule that can hydrogen bond to H2O is said to be
hydrophilic.
• In cholesterol, for example, the hydroxy group is hydrophilic, whereas the
carbon skeleton is hydrophobic.

hydrophilic part HO
hydrophobic part
(lipophilic)

cholesterol
• Triacylglycerols
– Function as an energy reserve.
– An ester composed of a molecule of glycerol and 3 molecules of
fatty acids.
• Fatty Acid Characteristics
– Unbranched carbon chains.
– Have an even number of
carbon atoms.
– Double bonds in unsaturated
acids are all cis.
• A trace percentage of
unsaturated acids found
naturally are trans.
 Table 12.5 Characteristics of the Major Types of Crystalline Solids
Interparticle Physical
Particles Forces Behavior Examples (mp,0C)

Atomic Atoms Dispersion Soft, very low mp, poor Group 8A(18)
thermal & electrical [Ne-249 to Rn-71]
conductors
Molecular Molecules Dispersion, Fairly soft, low to moderate Nonpolar - O2[-219],
dipole-dipole, mp, poor thermal & C4H10[-138], Cl2
H bonds electrical conductors [-101], C6H14[-95]
Polar - SO2[-73],
CHCl3[-64], HNO3[-
42], H2O[0.0]
Ionic Positive & Ion-ion Hard & brittle, high mp, NaCl [801]
negative ions attraction good thermal & electrical CaF2 [1423]
conductors when molten MgO [2852]
Metallic Atoms Metallic bond Soft to hard, low to very Na [97.8]
high mp, excellent thermal Zn [420]
and electrical conductors,
Fe [1535]
malleable and ductile
Network Atoms Covalent bond Very hard, very high mp,
usually poor thermal and
electrical conductors
Triacylglycerols (triglycerides)
• Fats and oils are triesters of glycerol and fatty
acids.
• Fats have higher melting points, making them
solids at room temperature.
• Oils have lower melting points, making them
liquids at room temperature.
• The melting point difference between fats and
oils correlates with the number of degrees of
unsaturation present in the fatty acid side chain.
As the number of double bonds increases, the
melting point decreases, as it does for the
constituent fatty acids as well.
• Solid fats have a relatively high percentage of
saturated fatty acids and are generally of animal
origin. Liquid oils have a higher percentage of
unsaturated fatty acids and are generally of
vegetable origin.
Triacylglycerols (triglycerides)

Fish oils, such as cod liver and herring oils, are very rich in
polyunsaturated triacylglycerols. These triacylglycerols pack so poorly that
they have very low melting points—they remain liquids even in the cold
water inhabited by these fish.
 Olestra

Product Warning: ―This Product Contains Olestra.

Olestra may cause abdominal cramping and loose
stools.‖

This condition (normally occurring only by excessive

consumption in a short period of time) became
popularly known as "anal leakage.‖

Olestra inhibits the absorption of some vitamins and

other nutrients. Vitamins A, D, E, and K have been
added.
saponification
Saponification of Triacylglycerols: Purification of Soap

How do you get rid of the glycerol?

 Purification of Soap

RCO2– Na + + glycerol

Solubility is an equilibrium process that follows LeChatelier’s Principle.

• To purify soap add one of the the products. The equilibrium will
shift to starting materials.
1. Boil in water.
2. Add NaCl.
3. Collect the solid.

RCO2– Na+(s) RCO2– (sol.) + Na+ (sol.)

• Water Solubility as a Result of Salt Formation
– Carboxylic acids will react with bases to form salts.
– These salts will be more water-soluble than the carboxylic acids were.
• Ion-dipole interactions with water. (Stronger than hydrogen-
bonding.)
– Water insoluble carboxylic acids can become soluble in aqueous
sodium hydroxide.

• Intermolecular forces between two molecules of carboxylic acid salts are

ion-ion.
• These forces are stronger than hydrogen bonding.
• Carboxylic acid salts have higher melting & boiling points than the
carboxylic acids they were made from.
Lipids can be categorized as hydrolyzable and nonhydrolyzable.
[1] Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis
with water. Many hydrolyzable lipids contain an ester unit.

[2] Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous

hydrolysis.
Waxes
• Waxes are esters (RCOOR’) formed from a high molecular weight
alcohol (R’OH) and a fatty acid (RCOOH).
• Usually complex mixtures of several esters along with unesterified
acids and alcohols.
• Lanolin, a wax composed of a complex mixture of high molecular weight
esters, coats the wool fibers of sheep.
• Spermaceti wax, isolated from the heads of sperm whales, is largely
CH3(CH2)14COO(CH2)15CH3. The three-dimensional structure of this
compound shows how small the ester group is compared to the long
hydrocarbon chains.
 Biological Uses of Wax

Protection against:
• parasites,
• mechanical damage,
• excessive water loss

Waterproofing of fur, feathers, skin

Lubrication
Pliability
Housing (Bees)
Phospholipids—Phosphoacylglycerols
 Transport Across Cell Membranes
• A cell membrane has to be semi-permeable–
• Some molecules can pass through, but not others.
• An impermeable membrane would not let any nutrients through, and a
permeable membrane wouldn’t be able to keep nutrients in (or let waste
products out).
• Substances can move through cell membranes by
• Passive transport–no energy is required to pass through.
• Molecules go from a region of higher concentration to a
region of lower concentration until the concentrations are
equal.
1. Simple diffusion–
• Small molecules dissolve in the cell membrane
and pass through.
• This is the method for most drugs.
2. Facilitated transport–the molecule is assisted by a
protein.
• This is the method for glucose.
• Active transport–energy is required to pass through.
• Molecules move from a region of low concentration to a
region of higher concentration.
 Active Transport

• It is essential for life that some solute concentrations be different

inside cells from outside.
• Different concentrations of a solute in the same system is called a
concentration gradient.
• Cells require a sodium/potassium gradient (high potassium
inside cells, high sodium outside cells).
• To maintain the concentration gradient against the natural
tendency to equalize the concentrations across the membrane,
cells use a protein called sodium-potassium ATPase.
• The energy from ATP-->ADP hydrolysis is used to change the
conformation of a membrane protein. This conformational
change transports sodium out and potassium inside the cell.
Sodium potassium ATPase

outside cell

cytoplasm

sodium ATP-->ADP potassium

Sodium
Postassium
ATPase
 Facilitated Transport CH2OH
O OH
OH
HO
HO
glucose glucose

outside cell

receptor 1, glucose binds

cytoplasm

2, glucose released
in cytoplasm

cytoplasm
 • The prosecution claimed that nicotine is
additive and that cigarettes were ―nicotine
Tobacco delivery devices.‖
Company • The CEOs of tobacco companies claim
Lawsuits that nicotine is not additive and is not
important.
• In a 60 Minutes interview and later in court
testimony, Jeffrey Wiegand, a tobacco
company biochemist, stated that
companies routinely treat tobacco leaves
with ammonia.
– ―Impact Boosting.‖
– This statement is proof that the
companies believed that nicotine
was important.
– (This was dramatized in the movie,
The Insider, staring Russell Crowe.)
• Why is this proof?
– Ammonia changed the intermolecular
forces of nicotine so that it could be
vaporized easier and absorbed faster
by the body.
 Nicotine

2 HCl
+
N N
N base + Cl– H
CH3 such as N – CH3
sodium hydroxide Cl
sodium bicarbonate
H

• Classes of Intermolecular Forces

– Ion-Ion
– Ion-Dipole
– Hydrogen Bonds
– Dipole-Dipole
– Dipole-Dispersion
– London Dispersion Forces
 2 HCl
+
N N
base + Cl– H
N CH3 N CH3
such as
sodium hydroxide Cl–
H
sodium bicarbonate
 Cocaine

Cl–
CH3 H CH3
N +N
CO2CH3 HCl CO2CH3
H H
O O
base
such as
H O sodium hydroxide H O
sodium bicarbonate
 Cl–
CH3 H CH3
N +N
CO2CH3 HCl CO2CH3
H H
O O
base
such as
H O sodium hydroxide H O
sodium bicarbonate
"crack cocaine" "cocaine"
isoprene

natural latex rubber

 Karen Wetterhahn CH3 Hg CH3

• An internationally known Professor of Chemistry and expert in the field of the effects of heavy metals
upon living systems, especially in their role in causing cancer.
• August 14, 1996. Wetterhahn spilled a small amount of dimethylmercury (1 or more drops) on her
gloved hand.
• January 1997. Symptoms appeared - tingly fingers and toes, slurred speech, problems with her balance,
and her field of vision started to shrink.
• January 28th 1997. Mercury poisoning was diagnosed. 4000 micrograms per litre, 80 times the toxic
threshold
• Two weeks later she entered into a coma from which she never recovered, dying on June 8th 1997.
• Tests subsequently showed that dimethylmercury would have penetrated the glove and started entering
her skin within 15 seconds.
• Only safe method to handle this compound is to wear highly resistant laminated gloves underneath a pair
of long-cuffed neoprene (or other heavy duty) gloves.
 Blood-Brain Barrier
• A layer of cells surrounding capillaries
that are in the brain.
• Protects the brain from unwanted
chemicals and pathogens.
• Far more selective for compounds
than other membranes.
• Cells even have enzymes to digest
unwanted compounds that might pass
through.
Eicosanoids
• Nonhydrolyzable lipids that are derived from arachidonic acid.
• Divided into 3 groups: leukotrienes, prostaglandins, thromboxanes.
• All are ―Local Hormones.‖
– Hormones are transported from the site of synthesis to the site of
action.
– Local hormones are synthesized where they are used.
• Control many functions including the pain & swelling of inflammation
responses found in rheumatoid arthritis. (See book for others.)
• Aspirin is an effective antiinflammatory.
• In early 1960s Ibuprofen & Naproxen were discovered. (NSAIDs)
• All had side effects including causing gastrointestinal bleeding.
• In the late 1960s it was discovered that these drugs work by blocking
cyclooxygenase enzyme (COX).
• Later work showed that there were 2 COX enzymes and these drugs
blocked both.
– COX-1 is widely distributed and among other things affects stability of
blood vessels.
– COX-2 seemed to be more important in the inflammation pathways.
– Make a drug that only blocks COX-2 and it may be a good pain reliever
with fewer side effects.
O
C
OH
H CH3 H CH3
O OH
C O
C H
C O
O CH3 O
CH3O
aspirin Ibuprofen Naproxen
 COX-2 Inhibitors
COX-2 Inhibitor Drugs
• Unfortunately some of them have been found to lead to increased risk of
heart attack and stroke.
• Some have been withdrawn.
• Some have been withdrawn and reintroduced.
• Steroids
– In plants and animals.
– Perhydrocyclopentanophenanthrene ring system.
– A few of the functions:
• Sex hormones
• D vitamins
• Bile acids
• Metabolism hormones
• Cell membrane components

CH3 H

H
CH3 CH3

H H
HO cholesterol
• Cholesterol
CH3 H
*
H
* *
• Cholesterol is the major steroid CH3 CH3
in animals. * *
• Little cholesterol is in plants * H * H
*
although plants do have HO cholesterol
steroids.
• Cholesterol has eight stereogenic carbons, so there are 28 = 256
possible stereoisomers. In nature however, only the stereoisomer shown
exists:
• Although cholesterol has been implicated in cardiovascular disease it is
essential to life because
• It is an important component in cell membranes.
• 25% of red blood cell membranes is cholesterol.
• It is the starting material for all other steroids.
• Humans do not have to ingest cholesterol because it is synthesized in
the liver and then transported to other tissues.
• Cholesterol is often found in the body as an aggregate with other lipids
and proteins.
• Much of the cholesterol in these aggregates is found as a cholesteryl
ester.
– Three types of aggregates are known & they are generally in micelle
form:
– Chylomicrons carry dietary lipids from the intestines to the tissues.
– High-density lipoproteins (HDLs) carry lipids from the tissues to the
liver for degradation and excretion.
– Low-density lipoproteins (LDLs) carry biosynthesized cholesterol
from the liver to tissues..
LDL
 O

SCoA +
thioester of a fatty acid
(an "activated" carboxylic acid) CH3 H

H
CH3 CH3
cholesterol
H H
HO

enzyme CH3 H

H
CH3 CH3
O
H H
O cholesteryl ester
LDL

Red Blood Cell

Atherosclerotic Plaque:
Deposited on the inside wall of an
artery, it is composed of mostly
cholesterol & its esters.
Cholesterol Biosynthesis
Mevalonate Biosynthesis
Statin Drugs
• Several drugs are now available to reduce the level of cholesterol in the
bloodstream.
• These compounds act by blocking the biosynthesis of cholesterol in its
early stages. Two examples are atorvastatin (Lipitor) and simvastatin
(Zocor).
Steroids
Fat Soluble Vitamins
• Vitamins are organic compounds required in small quantities for normal
metabolism.
• Since our cells cannot synthesize these compounds, they must be
obtained in the diet.
• Vitamins can be categorized as fat soluble or water soluble. The fat
soluble vitamins are lipids.
• Although fat soluble vitamins must be obtained in the diet, they do not
have to be consumed everyday. Excess vitamins are stored in fat cells,
and then used as needed.
• Because they can be stored, it is possible to overdose on these vitamins.
Steroids