Lipids and Cell Membranes
Lipids
•
Lipids: water-insoluble biomolecules that are
highly soluble in organic solvents
– Function as fuel molecules, highly concentrated energy
stores, signal molecules, and components of
membranes
•
Major classes
1.
2.
3.
4.
5.
Fatty acids and their derivatives
Fats/Acylglycerols/Triglycerides
Waxes
Phospholipids (phosphoglycerides and sphingomyelin)
Sphingolipids (including glycolipids and sphingosinebased molecules)
6. Terpenes or Isoprenoids, (including sterols/steroids)
The Fatty Acid Components of Lipids
Impart a Hydrophobic End
Fatty Acids
• In biological systems, contains even number of
carbon atoms, typically between 12 and 22
carbons
• The hydrocarbon chain is almost invariably
unbranched
• In most unsaturated fatty acids, the configuration
of the double bonds is cis
• In polyunsaturated fatty acids, the double bonds
are usually separated by at least one methylene
group
Fatty Acids
• The properties of fatty acids are dependent on
chain length and degree of unsaturation
• Short chain length and unsaturation enhance the
fluidity of fatty acids and of their derivatives
Naming Fatty Acids
• On Coconut Oil
C8 ...... 8.86 (Caprylic)
C10......6.17 (Capric)
C12......48.83 (Lauric)
C14......19.97 (Myristic)
C15......Traces (0.01)
C16.......7.84 (Palmitic)
C18.......3.06 (Stearic)
C18:2 ....0.76
C18:1.....4.44
C20........0.05 (Arachidic)
Fats or
Triacylglycerides
or Triglycerides
WAXES
• Esters of long alcohols and fatty acids
Beeswax
Carnauba
Leaf wax
Images From www.wikipedia.com
Phospholipids
• Has 4 components: fatty acids, a platform to
which the fatty acids are attached, a phosphate,
and an alcohol
• Abundant in all biological membranes
Phosphoglycerides
• Glycerol is the platform to which two fatty acids
and a phosphorylated alcohol are attached
• The simplest is phosphatidate, which is present
only in small amounts in membranes
The Major Phosphoglycerides
A special phospholipid: Sphingomyelin
• The platform is sphingosine instead of glycerol
Archaeal Lipids
• The nonpolar chains are linked to glycerol by ether
linkages
• Found in Archaebacteria
• The alkyl chains are branched and saturated
• The stereochemistry at the central glycerol carbon is
reversed
Sphingolipids: eg. glycolipids
• Sphingolipids: any lipid other than sphingomyelin that
has a sphingosine base
• Sphingosine + fatty acid + sugar
• In animal cells, glycolipids are derived from sphingosine;
the simplest is cerebroside
Multiple sclerosis
• MS affects the nervous
system; immune system
attacks myelin
• Affects eyes, muscle
control (movement,
speech, bladder & bowel
control)
• Richard Pryor, JK
Rowling’s mother, Alma
Moreno
Myelin sheath is
lipid-rich.
Destroyed sheath,
no sphingolipids->
disease
Terpenes/Isoprenoids
• Isoprene derivatives
Steroids
• A derivative of
terpenes
Cholesterol
• In the plasma membrane, cholesterol is oriented
parallel to the fatty acid chain of phospholipids
• Absent from prokaryotes
• Found in varying degrees in virtually all animal
membranes
• Major component of animal plasma membrane (30
to 40% of plasma membrane lipids)
• Its polar OH group gives it a weak amphiphilic
character
• Its fused ring system provides greater rigidity than
other membrane lipids
Steroid Hormones
• Cortisol – affects
carbohydrate, protein, and
lipid metabolism and
influence a wide variety of
vital functions (e.g.
inflammatory reactions and
the capacity to cope stress)
• Aldosterone – regulates the
excretion of salt and water
by the kidneys
• Testosterone and estrogen
– affect sexual development
and function
Membrane lipids
Biological Membranes
• Barriers that define the inside and the
outside of a cell
• Selective permeability
– Lipid components form the
permeability barrier
– Protein components act as
a transport system of pumps
and channels
Biological Membranes
• Internal and external membranes
have common features
• Functions in energy storage
and information transduction
Common Features of Biological
Membranes
1. Sheetlike structures, two molecules thick, that
form closed boundaries (Most are between 6
nm to 10 nm thick)
2. Consist mainly of lipids and proteins (mass
ratio changes from 1:4 to 4:1). Carbohydrates
present are linked to lipids and proteins
3. Membrane lipids are relatively small molecules
possessing both hydrophobic and hydrophilic
moieties
Common Features of Biological
Membranes
4. Specific proteins mediate distinctive functions
(May serve as pumps, channels, receptors,
energy transducers, and enzymes)
5. Membranes are fluid, noncovalent assemblies
6. Membranes are asymmetric
7. Membranes are fluid structures
8. Most cell membranes are electrically polarized
(typically -60 mV)
A Membrane Lipid is Amphiphatic
What Properties of Lipids Lead to
Membrane Formation?
• A Micelle
• Usually less than 20
nm
• A membrane bilayer
• Can be as large as
106 nm
What Properties of Lipids Lead to
Membrane Formation?
• The amphiphatic nature of lipids
• Why do most phospholipids and
glycolipids favor the formation of
a membrane bilayer instead of a
micelle?
– The two fatty acyl chains are too
bulky to fit into the interior of a
micelle
• The formation of the bilayer is a
self-assembly process driven
largely by hydrophobic
interactions
Properties of Lipid Bilayers
• The hydrophobic interactions lead to:
– A tendency to close on themselves so that
there are no edges; they form compartments
– Lipid bilayers are self-sealing
Lipid Vesicles
• Also called liposomes: aqueous compartments
enclosed by a lipid bilayer which can be used to
study membrane permeability or to deliver
chemicals to cells
Lipid Vesicles
• Can be formed by sonicating a phospholipid in
an aqueous media. The closed vesicles formed
are nearly spherical with a diameter of 50 nm
• Larger vesicles 1000 nm in length are formed
from a mixed solvent system by slow
evaporation of the organic solvent
Clinical Uses of Liposomes
• Clinical uses are under development
- Alters distribution of the drugs within the body
and lessens toxicity
- Liposomes concentrate in regions of
increased blood circulation
- Lipid vesicles fuse with particular kinds of
cells
Fusion of a Vesicle with
Plasma Membrane
• the inside of the vesicle and the
exterior of the cell are
topologically equivalent
• proteins bound for secretion
are packaged in membranous
secretory vesicles that
subsequently fuse with the
plasma membrane
Permeability of Membranes
• Studies using the planar bilayers show that
membranes have a very low permeability to ions
and most polar molecules
• Water readily diffuses because of its small size
Membrane Proteins
• Whereas membrane lipids form a
permeability barrier and thereby
establish compartments, specific
proteins mediate nearly all other
membrane functions
• Protein content of membranes vary
– 18% in myelin
– 50% in most cells
– 75% in energy-transduction membranes
(internal membranes of mitochondria
and chloroplasts)
Peripheral and Integral Membrane
Proteins
• Membrane proteins can be classified based on
how easily they can be dissociated from the
membranes
PERIPHERAL
-electrostatic and Hbond with head-groups
or integral proteins
INTEGRAL
-interaction with inner
hydrophobic chains
Integral Proteins May Be Alpha Helices
• Membrane-spanning alpha helices are the most
common structural motif in membrane proteins
A Channel Protein Can Be Formed from
Beta Strands
• Each strand is hydrogen bonded to its neighbor
in an antiparallel arrangement, forming a single
beta sheet
Ex. Porin
Part of the Protein Embedded
• Another role for alpha helices; a set of alpha
helices with hydrophobic surfaces extend from
the bottom of the protein into the membrane
Prostaglandin H2 synthase-1
Lipids and Many Membrane Proteins Diffuse
Rapidly in the Plane of the Membrane
• Lateral diffusion
• Fluorescence recovery after photobleaching
(FRAP)
Lateral and Transverse Diffusion
• Free lateral diffusion
• Transverse diffusion,
the transition of a lipid
from one face to the
other occurs once in
several hours
• Barrier of flip-flopping
for proteins are higher
– Preserves membrane
assymetry
Lipids and Many Membrane Proteins Diffuse
Rapidly in the Plane of the Membrane
• The diffusion coefficient of lipids in a variety of
membranes is about 1 square micrometer per
second. Thus a lipid can travel from one end of
a bacterium to the other in a second
• Some proteins are nearly as mobile as lipids
whereas others are virtually immobile. A mobile
protein has a diffusion coefficient of 0.4 square
micrometer per second
The Fluid Mosaic Model
• Proposed by Jonathan Singer and Garth
Nickolson based on the dynamic properties of
proteins in membranes
The Fluid Mosaic Model
• The essence of the model is that membranes
are two-dimensional solutions of oriented lipids
and globular proteins
• The lipid bilayer has a dual role:
– Solvent for the integral
membrane proteins
– A permeability barrier
The Phase-Transition, or Melting,
Temperature (Tm)
• Membrane processes
(transport, signal
transduction) depend
on the fluidity of
membrane lipids
• TM depends on the
length of the fatty acid
chain and on their
degree of unsaturation
The Melting Temperature of a
Representative Lipid
• The melting temperatures of
phosphatidyl choline containing
different pairs of identical fatty
acid chains are shown below
C’s DB’s Common Names Systematic Name Tm(0C)
22
0
Behenate
n-Docosanote
75
18
0
Stearate
n-Octadecanoate
58
16
0
Palmitate
n-Hexadecanoate
41
14
0
Myristate
n-Tetradecanoate
24
18
1
Oleate
cis-Δ9-Octadecenoate
- 22
Membrane Fluidity in Bacteria and
Eukaryotes
• Bacteria regulate the fluidity of their membranes
by varying the number of double bonds and the
length of their fatty acyl chain
– i.e. on going from 42 oC to 27 oC, the ratio of
saturated to unsaturated fatty acids decreases from
1.6 to 1.0
• In animals, the key regulator of membrane
fluidity is cholesterol
Cholesterol in Membrane
Lipids, Nutrition, and Health
Functions of Fats
• Used to build cells and parts of the cell (e.g. brain cells,
nerve tissues, cell membrane)
• Stored in the body in adipose tissue
– Adipose tissue are called fat depots
• Surround vital organs (e.g. heart, kidney, spleen) to
serve as protective cushion
• Stored under the skin for insulation
• Fat reserves are converted to glycerol and fatty acids ( 9
kcal per gram)
– Glycerol is burned for energy or converted to glucose
The human adipocyte
• Compose adipose tissue
• For storage and synthesis of
triacylglycerides, insulation, energy
storage (higher energy content than
glycogen)
• White fat cells: lipid droplet with
peripheral cytoplasm and nucleus;
semi-liquid fat with some sterol
derivatives
• Brown fat cells: lipid droplets
scattered, high mitochondria content
www.cnrs.fr, www.vulgaris-medical.com
Fats Transport
• Some important blood
lipoproteins
– Group of proteins with a
triglyceride or cholesterol
– Very-low density
lipoprotein (VLDL)
• Transport new triglycerides
from liver to adipose tissue
– Low density lipoprotein
(LDL)
• Transport cholesterol from
liver to cells
– High density lipoprotein
(HDL)
• Transport cholesterol from
tissues to liver
Atherosclerosis: Not just a
simple clogging problem!
From: http://www.nia.nih.gov/NR/rdonlyres/C3B176CB-3173-4F89-8FDA2774FB751108/4227/pic_atherosclerosis.jpg
Cholesterol biosynthesis
From: http://banon.cshl.edu/cgi-bin/eventbrowser?DB=gk_current&FOCUS_SPECIES=Homo%20sapiens&ID=191273&
Lowering cholesterol synthesis
• Use hypolipidemic drugs (eg. Statins)
• STATINS are HMG-CoA inhibitors
– Eg. Lovastatin
Table from: http://en.wikipedia.org/wiki/Statin
Crisco and Olestra (by P&G)
1911: Shortening
“To eat, or not to eat - fat is the question.”
- from the Introduction of Mary Enig, Know your Fats: The
Complete Primer for Understanding the Nutrition of Fats, Oils,
and Cholesterol, Bethesda Press, USA, 2000.
Olestra
• 1998, Proctor and Gamble introduced a
new fat/oil substitute called Olestra (brand
name Olean®
• material replaces fats in snack foods such
as potato chips
• claimed that food using Olestra in place of
digestible fats provide less calories since
the Olestra is not digested and passes
through the body unchanged
• Some side effects include abdominal
cramping and loose stools
Olestra
How does Olestra work?
http://www.cnn.com/HEALTH/9802/10/fakefat.olestra/olestra.large.jpg
Olean®
Olean®
http://static.howstuffworks.com/gif/question526-fat-chips.jpg
http://static.howstuffworks.com/gif/question526-olestra-chips.jpg
Carnitine Craze
• Responsible for
fatty acid transport
from cyosol to
mitochondria
where the FA is
metabolised
• Naturally
synthesized from
Lys and Met (Lisomer) in liver
and kidneys
Image from http://en.wikipedia.org/wiki/Image:AcylCoA_from_cytosol_to_the_mitochondrial_matrix.gif
Carnitine Craze
•
•
•
•
•
Highest amount in meat, dairy, nuts
Healthy individuals, including strict
vegetarians, generally synthesize
enough L-carnitine to prevent
deficiency.
The roles of L-carnitine
supplementation as an adjunct to
standard medical therapy in myocardial
infarction, heart failure, angina pectoris,
Alzheimer's disease, and HIV infection
require further research.
Although recent studies in rats suggest
acetyl-L-carnitine supplementation may
be beneficial in preventing age-related
declines in energy metabolism and
memory, it is not known whether acetylL-carnitine supplementation will help
prevent such age-related declines in
humans.
There is little evidence that L-carnitine
supplementation improves athletic
performance in healthy people.
Info from: http://en.wikipedia.org/wiki/Carnitine, The Linus
Pauling Institute (Oregon State University).
http://lpi.oregonstate.edu/infocenter/othernuts/carnitine/