Lipids

Dr. Diala Abu-Hassan, DDS, PhD

[email protected]
Medical Students- Summer
Semester 2015
Images were taken Campbell textbook or 1
McMurryetal Dr. Diala Abu-Hassan
 Lipids- Definition
• Naturally occurring organic molecules that are
nonpolar and therefore dissolve in nonpolar
organic solvents but not in water.
• Many lipids have hydrocarbon or modified
hydrocarbon structure, properties, and
behavior

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 Major role of lipids
• Energy storage from metabolism
of food within fat cells
(adipocytes).
• Separate the inside and outside
of the cells as part of all cell
membranes. Adipocytes

• Chemical messengers in the

endocrine system and elsewhere.

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Lipid families

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 Fatty Acids
-Are long, unbranched
hydrocarbon chains with a
carboxylic acid group at one end.

-Most have even numbers of

carbon atoms.

-May or may not contain carbon

carbon double bonds.

-Saturated fatty acids (without

double bonds)

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 Fatty Acids
-Unsaturated fatty acids (with double bonds)

- The stereochemistry at the double bond is usually cis rather

than trans

Monounsaturated versus polyunsaturated fatty acids

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Common fatty acids

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 Properties of Fats and Oils
• Melting point decreases with the presence of more double
bonds a fatty acid has.
• Vegetable oils are lower melting than animal fats because
oils have more unsaturated fatty acids than animal fats.

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 Triacylglycerols
• All fats and oils are composed of triesters of glycerol with
three fatty acids.
• Glycerol (glycerine) is 1,2,3-propanetriol
• The 3 fatty acids can be the same or different.

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Example of a triacylglycerol

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Oil and fat are mixtures of
triacylglycerols

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Triacylglycerols from a fat and an oil

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 Properties of Triacylglycerols
• Uncharged, nonpolar, hydrophobic molecules.
• No ionic charges
• Solid triacylglycerols (fats) high proportion of
saturated fatty acid chains
• Liquid triacylglycerols (oils) high proportion of
unsaturated fatty acid chains

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 Roles of TAGs
• The primary function of
triacylglycerols is long-term
storage of energy for the
organism

• Adipose tissue provides

thermal insulation and
protective padding

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 Chemical Reactions of TAGs
Hydrogenation

Margarine

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 Hydrolysis of TAGs (Saponification)

• Esters can react with water

(hydrolyzed) to form their carboxylic
acids and alcohols.

• Lipases catalyze hydrolysis of dietary

fats and oils in the body.

• Saponification is the hydrolysis of fats

and oils by strong aqueous bases
(NaOH or KOH)

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 Detergents
• Anything that washes away dirt

• How do soaps and detergents act?

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 Phosphoglycerols (Phosphatidyl esters)
(Glycerophospholipids)

Phosphoric acid is triprotic and thus can form more than one
ester linkage.
Different R groups result in different types of phosphoglycerols
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 Types of Phosphoglycerols
-The nature of the second alcohol esterified to the phosphoric
acid determine the type of phosphoglycerol.
-Phosphoacylglycerols are important components of biological
membranes.

Phosphatidylcholine (lecithin)

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 Types of Phosphoglycerols

Phosphatidylethanolamine (cephalin)

Phosphatidylserine

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 Types of Phosphoglycerols
Phosphatidylglycerol

Diphosphatidylglycerol
(Cardiolipin)
found almost exclusively in the
inner mitochondrial membrane

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 Types of Phosphoglycerols
Phosphatidylinositol

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 Waxes
• Waxes are complex mixtures of esters of long-
chain carboxylic acids and long chain.
• Beeswax, protective coatings on most fruits,
aquatic birds feathers, etc

From whales, cosmetics

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 Sphingolipids
• Abundant in the nervous system

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 Sphingomyelin and multiple sclerosis
(MS)
• Myelin sheath consists of many
layers of plasma membrane (rich in
lipids not proteins) that have been
wrapped around the nerve cell.

• Loss of myelin leads to the slowing

and eventual cessation of the
nerve impulse.

• In MS, the myelin sheath is

progressively destroyed by sclerotic
plaques that affect the brain and
spinal cord.

• Weakness, lack of coordination,

and speech and vision problems

Dr. Diala Abu-Hassan health.howstuffworks.com

 Sphingolipids-Glycolipids

Sugar

Glycolipids act as markers

on cell membranes and
play a role in tissue and
organ specificity
Ceramide + glucose = glucocerebroside
Types of cerebrosides
Ceramide + galactose= galactocerebroside

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 Glycolipids-Gangliosides

Complex sugar
(>3 sugars)

Gangliosides are present in large quantities in nerve tissues

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Glycolipids-Gangliosides

Sphingosine

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Membrane lipids

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 Steroids

Sex hormones

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 Cell Membrane Lipids
Cholesterol
• A steroid
• 4 fused rings- flat shape
• Membrane fluidity
• A component of cell
membranes
• A precursor of other steroids
and of vitamin D3.
• Is modified in liver cells to produce bile acids, essential in
the digestion of dietary fats.
• 800 mg/day
• Has a role in the development of atherosclerosis
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31
 Eicosanoids: Prostaglandins and Leukotrienes

• Local hormones (paracrine)

• Arachidonic acid derivatives

(20:4)

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 Prostaglandins (PGs)
Different PGs differ in the
numbers and positions of
double bonds and oxygen-
containing functional groups.

Functions: Control of blood

pressure, stimulation of
smooth-muscle contraction,
induction of inflammation, and
inhibit the aggregation of
platelets.

Cortisone and other steroids also have anti-inflammatory effects because of their
inhibition of PG synthesis.

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 Clinical application

Aspirin inhibits PG synthesis, particularly in blood platelets,

accounting for its anti-inflammatory and fever-reducing properties.

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 Leukotrienes (LK)
• Function: constriction of smooth
muscle, especially in the lungs.

• In asthma, allergic reactions to

pollens increase LK C synthesis
resulting in airway constrictions.

• Drugs that inhibit the synthesis of

leukotriene C or block its
receptors are used in the
treatment of asthma

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 Thromboxanes
• Arachidonic acid
derivatives.
• They contain cyclic
ethers.
• Ex. thromboxane A2
(TxA2) induces
platelet aggregation
and smooth-muscle
contraction.

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Lipid-Soluble Vitamins
• Vitamin A, D, E and K

• Hydrophobic

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 Lipid-Soluble Vitamins
Vitamin A or retinol
• β-carotene is the precursor of vitamin A
• β-carotene is an unsaturated hydrocarbon

• Vitamin A is oxidized to retinal that reacts with opsin to form

rhodopsin
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 Lipid-Soluble Vitamins
Vitamin D
• Has several
forms such as,
vitamin D3
(cholecalciferol)

• Vitamin D3 is formed from

cholesterol by the action of UV
radiation from the Sun
• Vitamin D3 increases a Ca2+ binding
protein synthesis that increases
dietary calcium absorption in the
intestines resulting in Ca uptake by
the bones.

• Rickets
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 Lipid-Soluble Vitamins
Vitamin E
• The most active form of
vitamin E is α-tocopherol

•
An antioxidant (a good
reducing agent) to protect
important compounds, such
as vitamin A, from
degradation and to react
with and remove free
radicals.
• b
• A free radical are very reactive because it has at least one unpaired electron

• Free radicals play a role in the development of cancer and in the aging process.

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Lipid-Soluble Vitamins
Vitamin K
• From the Danish Koagulation
• A long unsaturated hydrocarbon side
chain consists of repeating isoprene
units
• The number of isoprene units
determines the exact form of vitamin K.

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 Vitamin K and coagulation
• The anticoagulants, dicumarol and warfarin (a rat poison), are
vitamin K antagonists

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 Biological membranes
• Roles:
• 1. Separate cells from the external environment
• 2. Transport of specific substances into and out of cells.
• 3. Many important enzymes are found in membranes

• Phosphoglycerides are the principal lipid components of

membranes

Lipid bilayer Cell membrane

• The protein component of a membrane can form 20% to 80% of its

total weight

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The structure of cell membrane: fluid-mosaic model

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The lipid bilayer
Bulkier molecules (e.g.
cerebrosides) tend to occur
in the outer layer, and
smaller molecules tend to
occur in the inner layer.

Because the bilayer is

curved, the molecules of the
inner layer are more tightly
packed

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Fatty acids and membrane fluidity

Highly fluid membrane

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How does the composition of the bilayer affect
its properties?

• -The bilayer’s fluidity

depends on its composition

• -Saturated fatty acids, more

packing and rigidity

• -The lipid bilayer

components are always in
motion (more movement in
more fluid bilayers than rigid
ones)

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The effect of cholesterol on membrane
fluidity

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Membrane gel-to-liquid crystalline
phase transition

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 Lipid molecule movement within
membranes

• Occasional “flip-flop” migration of lipid molecules

from one layer of the bilayer to another.

• Lateral motion of lipid molecules within one of the

two layers frequently takes place especially in more
fluid bilayers.

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 The Kinds of Membrane Proteins
1. Peripheral proteins on the surface of the membrane
• Are usually bound to the charged head groups of the lipid
bilayer by polar interactions, electrostatic interactions, or both.
• Can be removed by mild treatment

2. Integral proteins within the lipid bilayer

• Removal from membranes is difficult and needs harsh
conditions, such as treatment with detergents or extensive
sonication (these techniques result in denaturation)

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 Protein Attachment to Membranes
• Proteins span membranes in the form of an a-helix or b-sheet.

• Proteins anchoring to
lipids via covalent bonds
from cysteines or free
amino groups on the
protein to lipid anchors.

• Lipid anchors: myristoyl

and palmitoyl groups

• Proteins and lipids are

unevenly distributed on
the inner and outer
layers of cell membranes

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 Clinical application: Membranes and drug
delivery

Example: a skin lotion to counteract the effects of UV light on DNA repair

The lotion contains liposomes filled with a viral DNA-repair enzyme, called T4
endonuclease V.
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 Functions of proteins
1. Structural boundaries and containers of all cells and
of organelles

2. Transport through the lipid bilayer or membrane

proteins.

3. Catalysis

4. Receptor property

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Transport through membranes

1. Passive transport
including simple and
facilitated diffusion

2. Active transport

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 Facilitated diffusion

-Carrier proteins have several a-helical portions that span the membrane; or a
b-barrel that forms the pore.
-The exterior of the helix (in contact with the lipid bilayer), is hydrophobic.
-The interior of the helix (through which ions pass) is hydrophilic.
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 Active transport
• A carrier protein
and an energy
source to move
solutes against a
gradient are needed

• EX. Na+/K+ pump

(ATPase and a
transport protein)

• Primary active transport,

the movement of molecules
against a gradient is directly
linked to the hydrolysis of a
high-energy molecule, such
as ATP.
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Secondary Active transport

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 How do membrane receptors work?

• Many receptors are tightly bound integral proteins, and their

activity depends on the membrane environment.

• Receptors are often large oligomeric proteins (several

subunits), with molecular weights of hundreds of thousands.

• Receptors have very few molecules in each cell, making their

isolation and studying more difficult

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 How do membrane receptors work?
• LDL is a particle that
consists of various lipids,
cholesterol and
phosphoglycerides, and a
protein

• LDL is the principal carrier

of cholesterol in the
bloodstream

• Excess cholesterol inhibits

LDL receptor synthesis and
increases cholesterol
concentration in blood.

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