Lipids

Characteristics:

• Oils, fats

• Some vitamins, hormones

• Not polymeric

• Aggregate
– Structural matrix of biological membranes
 Importance
• Energy storage
– Fatty acids
– Triacylglycerols

• Structural
– Phospholipids
– Glycolipids
– Sterols

• Other lipids
– Fat-soluble vitamins (A,D,E,K)
 Fatty Acids

• Simplest type; components of more complex lipids

• Carboxylic acids with long aliphatic hydrocarbon chains
• Generally 10-20 carbons
– Most common are 16, 18
– Mostly even number due to synthesis
• Saturated or unsaturated
 Saturated Fatty Acids

• Only C─C (single bonds)

• Highly flexible
• Most stable conformation: fully extended
• mp increase with chain length
• example: stearic acid (octadecanoic acid)

O OH

1
18
 Unsaturated Fatty Acids
• Contains C═C
• Can be polyunsaturated
– essential FAs
• First double bond typically at C9
– D9
• Double bonds every three carbons
– D9,12
– ─CH═CH─CH2─CH═CH─CH2─
• examples: oleic acid (18:1) and linoleic acid (18:2)

18
OH
OH
O 1
18 O 1

12
9
9
 Omega-3 Fatty Acids

• In: corn and fish oils

• Reduce possibility of heart disease
– Don’t stick to walls of blood vessels
– Promote blood flow
• example: linolenic acid

18

O OH

1
 Unsaturated Fatty Acids
• Double bond:
– Usually of the cis type.
– Causes bend in hydrocarbon chain
– Do not pack as well as saturated FAs
– mp decrease as unsaturation increases
8
 Lipid classes: Triacylglycerols

• Also known as triglycerides

• Fatty acid triesters of glycerol
• Simple (one FA type, tripalmitin)
• Mixed (> 1 FA type, below)
 Triacylglycerols

• Most abundant class of lipids in animals

• mp determined by degree of unsaturation
• More unsaturation in plants than in animals
• Function = energy reserves, insulation
– Richer source of energy than carbohydrates
• Stored in adipocytes throughout the animal body
– Hydrolyzed by lipases as needed
 Phospholipids
• Contain phosphodiester bond
– Negative charge at physiological pH
• Example: Glycerophospholipids
– Also known as phosphoglycerides
– Major component of membranes (structural
lipids)
– Esterified glycerol-3-phosphate
• Phosphoryl group linked to polar group (various
structure)
 O

O H2C O C R2

R1 C O CH O

H2C O P O X

O
glycerophospholipid

In most glycerophospholipids (phosphoglycerides),

Pi is in turn esterified to OH of a polar head group (X):
e.g., serine, choline, ethanolamine or inositol.
The 2 fatty acids tend to be non-identical. They may
differ in length and/or the presence/absence of double
bonds.
 O

O H2C O C R2

R1 C O CH O

H2C O P O

O H

OH OH
H OH
OH H
phosphatidyl- H H
inositol
H OH

Phosphatidylinositol, with inositol as polar head

group, is one glycerophospholipid.
In addition to being a membrane lipid,
phosphatidylinositol has roles in cell signaling.
 O

O H2C O C R2

R1 C O CH O CH3
+
H2C O P O CH2 CH2 N CH3

O CH3

phosphatidylcholine

Phosphatidylcholine, with choline as polar head

group, is another glycerophospholipid.
It is a common membrane lipid.
 O

O H2C O C R2
Each glycerophospholipid R1 C O CH O
includes
H2C O P O X
 a polar region:
O
glycerol, carbonyl O glycerophospholipid
of fatty acids, Pi, & the
polar head group (X)
polar
 non-polar hydrocarbon
tails of fatty acids (R1, "kink" due to
double bond non-polar
R2).
 Glycolipids:
• Monosaccharide or
oligosaccharide at
polar end
• Example:
Galactolipids
– Galactose residues
– Glycosidic linkages to
C3 of 1,2-
diacylglycerol
– Plant cells
• Internal membranes
of chloroplasts
 Sphingolipids:
• Also major components of membranes
• Phospholipid or glycolipid (depends on polar
group)
• Derivatives of sphingosine (instead of glycerol)
– C18 amino alcohol
• Ceramide
– Acylated sphigosine
– Parent compound of most abundant
sphingolipids
Phospholipid

Phosphate derivative
structurally similar to
glycerophospholipids

monosaccharide
Glycosphingolipids

neutral; 2 or more
sugars (Glc, Gal, or
GalNac)

oligosaccharide; N-
acetyl neuraminic
acid; negative at pH
7
 CH3 O
H2 H2 
+
H3C N C C O P O
Sphingomyelin has a
CH3 O OH
phosphocholine or
phosphethanolamine phosphocholine H
H2C C CH
head group.
sphingosine NH CH
Sphingomyelins are
common constituent of O C HC
plasma membranes fatty acid R (CH2 )12
Sphingomyelin CH3

Sphingomyelin, with a phosphocholine head group, is similar in size and shape to the
glycerophospholipid phosphatidyl choline.
 Glycerophospholipids/Sphingolipids:
 Structural similarities
 CH2OH
A cerebroside is a
sphingolipid (ceramide) OH O
with a monosaccharide H OH
such as glucose or galactose OH H O
H
as polar head group. H H H2C C CH

H OH NH CH

O C HC

R (CH2 )12
cerebroside with
-galactose head group CH3

A ganglioside is a ceramide with a polar head group that is a complex

oligosaccharide, including the acidic sugar derivative sialic acid.

Cerebrosides and gangliosides, collectively called glycosphingolipids,

are commonly found in the outer leaflet of the plasma membrane
bilayer, with their sugar chains extending out from the cell surface.
 Isoprenoid lipids (Terpenes)

• Terpenes are lipids composed of repeating five-carbon units

called isoprene units.
• An isoprene unit has five carbons: four in a row, with a one-
carbon branch on a middle carbon. One of the actual in vivo
precursors of isoprenoids is isopentenyl pyrophosphate

• Terpenes include essential oils, some vitamins, steroids

(sterols), carotenoids and many other important classes of
compounds.

22
Terpenoid (Isoprenoid) Lipids:
 Sterols
• Sterol
– Four fused rings
• Greater rigidity than other
membrane lipids
– One or more hydroxyl groups
• Gives amphipathic
character
– Hydrocarbon side chain
• Cholesterol
– Most abundant sterol in
animals
– Produced by liver; supplied by
diet
– High levels lead to gallstones
and deposits on arteries
(plaque)
 Sterols
• Metabolic precursors of
steroid hormones
– Regulate physiological
functions
– Androgens (testosterone)
– Estrogens (b-estradiol)
– Glucocorticoids (cortisol)
• Insoluble in water
• Bind to proteins for
transport to target tissue
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 every day. Excess vitamins are stored in fat cells,
and then used as needed.

26
The fat soluble vitamins:

27
 Student activities
• What is eicosanoids? Explain.
• What are their biological activity?
 Lipid Digestion & Transport

Digestion & transport of lipids poses unique

problems relating to the insolubility of lipids in
water.
Enzymes that act on lipids are soluble proteins or
membrane proteins at the aqueous interface.
Lipids, & products of their digestion, must be
transported through aqueous compartments within
the cell as well as in the blood & tissue spaces.
 Bile Acids O

C O R2
R1
CH3

CH3

HO OH
H R1 = OH or H
R2 = H or NHCH2COOH or NHCH2CH2SO3

Bile acids (bile salts) are polar derivatives of cholesterol,

formed in liver and secreted into the gall bladder.

They pass via the bile duct into the intestine, where they aid
digestion of fats & fat-soluble vitamins.

Bile acids are amphipathic, with detergent properties.

 Bile Acids O

C O R2
R1
CH3

CH3

HO OH
H R1 = OH or H
R2 = H or NHCH2COOH or NHCH2CH2SO3

Bile acids emulsify fat globules into smaller micelles,

increasing the surface area accessible to lipid-hydrolyzing
enzymes.

They also help to solubilize lipid breakdown products (e.g.,

mono- & diacylglycerols from triacylglycerol hydrolysis).
 Apoprotein B-100
Shorter free
fatty acids are monolayer of
transported in phospholipid &
the blood bound cholesterol
to albumin, a
serum protein core: cholesteryl
esters & some
secreted by
triacylglycerols
liver.
LDL
Other lipids are transported in the blood as part of
lipoproteins, complex particles whose structure
includes:
 a core consisting of a droplet of triacylglycerols
and/or cholesteryl esters
 a surface monolayer of phospholipid, cholesterol, &
specific proteins (apolipoproteins), e.g., B-100.
Lipoproteins differ in the ratio of protein to lipids, & in
the particular apoproteins & lipids that they contain.
They are classified based on their density:
 Chylomicron (largest; lowest in density due to high
lipid/protein ratio; highest % weight
triacylglycerols)
 VLDL (very low density lipoprotein; 2nd highest in
triacylglycerols as % of weight)
 IDL (intermediate density lipoprotein)
 LDL (low density lipoprotein, highest in cholesteryl
esters as % of weight)
 HDL (high density lipoprotein; highest in density
due to high protein/lipid ratio)
 Lipids and cell membranes

• Membranes organize the chemical activities of

cells.
• The outer plasma membrane
– forms a boundary between a living cell and its
surroundings
– Exhibits selective permeability
• Controls movement of molecules in and out of
the cell
• Internal membranes provide structural order for
metabolism
• Form the cell's organelles
• Compartmentalize chemical reactions
Characteristics of membrane lipids

1. Selective permeability

2. Membrane fluidity

3. Self - sealing capability

4. Asymmetry
 Selective permeability
• Hydrocarbon chain (hydrophobic)–
impenetrable barrier to ionic and polar
substances

• Specific membrane protein –regulate

movement of substances into and out
of cells
 Cell membranes
Plasma membrane is about 50 atoms thick and serves as a selective barrier.
Eucaryotic cells contain many
compartments created by
intracellular membranes
• The lipids in the cell membrane are amphipathic

• Phosphatidylcholine is the most common type of phospholipid.

Positive
negative
Three kinds of membrane lipids, all amphipathic, include phospholipids,
sterols, and glycolipids.

Hydrophilic heads
Purely
hydrophobic
molecules
coalesce into a
single drop in
water.

Amphipathic molecules like

phosphotidylethanolamine
form a lipid bilayer -
energetically most favorable.
Phospholipids form double-layered biological membranes, e.g. the plasma
membrane that surrounds living cells and controls movement of substances in and
out of the cell
Membrane is a collage of proteins & other molecules embedded in the
fluid matrix of the lipid bilayer

Glycoprotein Extracellular fluid

Glycolipid

Phospholipids
Cholesterol
Transmembrane
proteins
Peripheral
protein
Cytoplasm Filaments of
cytoskeleton
 Membrane fluidity
• Fluidity-resistance of membrane components to
movement

• Rapid lateral movement Rotation

• High unsaturated chain = Flip-flop

More fluid membrane

• Cholesterol moderates membrane

stability Lateral
diffusion
• Membrane fluidity is important to a cell for
many reasons.
– 1. Enables membrane proteins to diffuse
rapidly and interact with one another -
crucial in cell signaling etc.
– 2. Provides a simple means of distributing
membrane lipids and proteins by diffusion
from sites of insertion.
– 3. Allows membranes to fuse with one
another and mix their molecules
– 4. Ensures that membrane molecules are
distributed evenly between daughter cells.
• Remember though, cell has control -
cytoskeleton and other interactions can limit the
mobility of specific lipids and proteins.
• The fluidity of a lipid bilayer depends on its
composition.

– As temperature and environment changes,

the fluidity of the cell’s membranes must be
kept functional.

– The closer and more regular the packing of

the tails, the more viscous and less fluid the
bilayer will be

– The length and degree of saturation with

hydrogens affect their packing
• shorter tails can not interact as much - more fluid
• one of the two hydrocarbon tails often has a double
bond – unsaturated (usually cis). This creates a
kink - less packing, more fluid.
Plant fats are generally unsaturated and are liquid at room temperature.
Animal fats (contain more saturated fatty acids) are solid at room temperature.
• In bacterial and yeast cells, both the
lengths and the unsaturation is
constantly adjusted to maintain the
membrane at a relatively constant
fluidity.
– At higher temperatures the cell makes
longer tailed lipids with fewer double
bonds.
• In animal cells, membrane fluidity is
modulated by cholesterol, which is
absent in plants, yeast and bacteria.
Cholesterol fills in the spaces left by the kinks; stiffens the bilayer and makes it
less fluid and less permeable.
Self-sealing capability
 Asymmetry

• Biological membrane – asymmetry

• Lipid composition of each half –bilayer different

• Originate during membrane assembly

phospholipid biosynthesis occurs on only one side of
a membrane

• Significance is not yet clear

Membrane proteins
• Embedded in the bilayer are proteins

– Most of the membrane’s functions are

accomplished by the embedded proteins.
• Integral proteins span the membrane
• Peripheral proteins are on one side or the
other of the membrane
 Membrane Proteins

Examples of membrane protein types:

1. Recognition proteins
2. Enzymes
3. Receptor proteins
4. Transport proteins
– Passive and active
 Fluid Mosaic Model of the plasma membrane

• A membrane is a mosaic
– Proteins and other molecules are embedded in a
framework of phospholipids
• A membrane is fluid
– Most protein and phospholipid molecules can
move laterally
• Recognition Proteins - identify type of cell and
identify a cell as “self” versus foreign
– Most are glycoproteins
• Carbohydrate chains vary between species,
individuals, and even between cell types in a
given individual.
• Glycolipids also play a role in cell recognition

• Receptor proteins bind hormones and other

substances on the outside of the cell.
– Binding triggers a change inside the cell.
• Called signal transduction
• Example: The binding of insulin to insulin
receptors causes the cell to put glucose
transport proteins into the membrane.
 Messenger molecule

Receptor

Activated
molecule
 Transport Proteins

• Passive Transport Proteins

– allow water soluble substances (small polar
molecules and ions) to pass through the
membrane without any energy cost

• Active Transport Proteins

– The cell spends energy to transport water
soluble substances against their concentration
gradient
Plasma Membrane

– Glycoproteins and glycolipids are

proteins/lipids with short chain carbohydrates
attached on the extracellular side of the
membrane.
Fig. 5-1a
Carbohydrate of
glycoprotein

Glycoprotein

Glycolipid

Integrin

Phospholipid
Microfilaments
of cytoskeleton Cholesterol
Glycoproteins, proteoglycans and glycolipids: found on the noncytosolic
side of the lipid membrane. They form a sugar coating called the glycocalyx.

Glycocalyx helps to
protect the cell
surface from
mechanical and
chemical damage,
absorb water and
give the cell a slimy
surface to help
cells squeeze
through narrow
spaces and prevent
them from sticking
to each other or to
the walls of blood
vessels.
Besides protection and lubrication, the glycocalyx is important in cell-cell
recognition and adhesion. Some proteins (lectins) recognize particular
oligosaccharide side chains and bind to them. The short oligosaccharides are
enormously diverse, joined in different ways, branched, very complex and hard
to study. Example of recognition: recognition of an egg by a sperm.

Specific carbohydrate
chains on the surface of
neutrophils(white-blood-
cell type) bind a lectin on
the cells of the blood
vessels at the site of
infection, allowing them
to stick transiently. In this
way the phagocytes enter
and ingest the bacteria.