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DBT2117: Biochemistry (I)
Lecture 17
Lipids
• Understand and familiarize the nomenclature of fatty acids
• Understand the structure of lipids and their characteristics
• Understand how lipids make membranes
• Membrane associated protein / transmembrane proteins
• Molecular transport across membrane occurs via several mechanisms
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Occurrence of lipids in biology •
Lipids are a broad group of molecules with the characteristics of having long
hydrophobic carbon chains
•
Lipid molecules are commonly found in fats, oils, waxes, certain vitamins (A, D,
E, etc), soaps (detergents), etc…
•
Most significant function of lipids for biology is the formation of membranes
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The Molecular Structure and Behavior of Lipids •
Lipid monomer in general contain both a
hydrophilic head and a hydrophobic tail
•
Typically a lipid molecule is insoluble in water
(due to the long hydrophobic tail).
•
•
•
Polar or charged functional groups
HOWEVER! Lipids associate with each
other and form water soluble structures
by displaying hydrophilic head on the
outside (in aqueous solution)
These structures include:
• Micelles
• Vesicles
• Bilayers
Nonpolar carbon
Chain(s)
Note: when lipids are used to make energy
storage, they are turned into insoluble oils.
Hydrophobic effect
•
Hydrophobic compounds aggregates in aqueous solution and exclude water out.
•
Recall that this phenomenon is due to maximizing water entropy
http://photographyblogger.net/18‐interesting‐pictures‐of‐oil‐in‐water/
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Structures of water soluble lipids
Micelles:
•
Na+
Na+ Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
2 layers:
Outside aqueous (water)
Inside organic (oil)
Na+
Na+
Na+
Na+
Na+
Na+
Na+
+
Na+ Na
Vesicles
•
3 layers:
Outside aqueous (water)
Middle layer organic (oil)
Inside aqueous (water)
Bilayers (cell membrane)
•
Basically almost the same as
vesicles…
Simplest lipid monomer: Fatty acids
•
Fatty acids can make up other more complex lipids such as triacylglycerides
•
Fatty acids are long carbon chain carboxylic acids typically with even number carbons
•
Can be either
• Saturated – only (C‐C) Carbon SINGLE bonds through out chain
• Unsaturated – contains (C=C) Carbon DOUBLE bonds (one or more)
•
•
In nature, unsaturated fatty acids are mainly cis‐fatty acids
Trans‐fatty acids are synthetically produced as a side contaminating product of food
industry. Consumption of these fatty acids increases risk to heart diseases.
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Unsaturated fatty acids – essential diet for humans
•
Humans can make saturated fatty acids and most other fatty acids needed by our body by
metabolizing carbohydrates and proteins (sources of carbon, hydrogen, and oxygen)
•
However! We cannot synthesize omega‐3 and omega‐6 unsaturated fatty acids
•
We need omega‐3 and omega‐6 to synthesize hormone‐like molecules called eicosanoids.
Eicosanoids help regulate blood clotting, blood pressure, immune function, and other body
processes
ω‐9
ω‐6
ω‐3
E. Generalic, http://glossary.periodni.com/glossary.php?en=fatty+acid
Distribution of fatty acids in common cooking oil
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How to represent fatty acids
X:Y (c/t) Δn,n,n
18:3c Δ9,12,15 •
•
•
•
•
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18 carbons in total length
3 unsaturated bonds
c for cis‐unsaturation
9,12,15 are position of the C=C double
bonds
Covalently bonded fatty acids: triacylglycerides
•
Triacylglyceride (also known as: triacylglycerol, triglyceride, TAG) is an ester of
glycerol + 3 fatty acids
glycerol
Just as with sugars, in order for this reaction to occur… glycerol & fatty acid have to be “activated”
We will talk more about this when we talk about lipid biosynthesis •
Note that the original hydrophilic head is gone after
bonding with glycerol
•
•
TAG is water insoluble
TAG form oil droplets inside of cells (adipocytes)
of adipose tissues
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Functions of fat storage in animals
1. Energy production ‐ most fat in most animals is oxidized for the generation of
ATP, to drive metabolic processes.
2. Heat production ‐ specialized cells (in “brown fat” of warm‐blooded animals, for
example) oxidize triacylglycerols for heat production, rather than to make ATP.
3. Insulation ‐ in animals that live in a cold environment, layers of fat cells under
the skin serve as thermal insulation. The blubber of whales is one obvious
example.
Not all triacylglycerides are the same
•
Consider animal fat and vegetable oil…
•
Both are triacylglycerides, how come animal fat is solid at room temperature
while vegetable oil is liquid?
VS.
•
Answer is in the saturation of the fatty
acid that make up the fat/oil
•
Unsaturated fatty acids increases the
fluidity of the TAG
• This property is due to the “kinks”
that C=C bond causes in packing.
Presence of C=C causes them to
pack less well…
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Soaps and detergents
• Soap is fatty acid salt.
• When fats are hydrolyzed with strong bases such as NaOH or KOH (in earlier times, wood ashes were used), a soap is produced.
• This process is called saponification.
• The fatty acids are released as either sodium or potassium salts, which are fully
ionized.
• However, as cleansers, soaps have the disadvantage that the fatty acids are precipitated by
the calcium or magnesium ions present in “hard” water, forming a scum and destroying the
emulsifying action.
•
To circumvent that, synthetic detergents are developed.
• A classical example is SDS (Sodium dodecyl Sulfate), a common detergent used in
biochemical research for analyzing proteins.
How soaps are made
Small companies: batch production
Large companies: continuous production
http://www.madehow.com/Volume‐2/Soap.html
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Waxes
•
Wax is an ester formed by fatty acid and fatty alcohol
•
Wax occurs naturally in plants & fruits
•
Wax is generally completely water insoluble
•
As with the triacylglycerols, the firmness of waxes increases with
chain length and degree of hydrocarbon saturation.
Biological membranes
•
In most case, lipid molecules that make up the membrane contains:
• One highly polar head group
• TWO hydrophobic tails
•
2 hydrophobic tails are typically observed and makes sense because of its shape…
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Biological membranes
•
•
Four major classes of membrane‐forming lipids:
•
Glycerophospholipids
• Glycerol as backbone + phosphate‐containing head group
•
Glycoglycerolipids
• Sugar containing glycerolipids
•
Sphingolipids
• Sphingosine based
•
Glycosphingolipids
• Sugar containing sphingo based lipid
Cholestrols are also commonly found in animal membranes
Composition of some biological membranes
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Stereochemistry of glycerophospholipids
• Glycerol is a prochiral molecule.
• Phosphorylation of one CH2OH group or the other gives the R‐ or S‐enantiomer of
glycerol phosphate.
• The same molecule can be called L‐glycerol‐3‐phosphate or D‐glycerol‐1‐phosphate
depending on the carbon numbering scheme.
Same thing can have two names…
Standardize nomenclature – sn convention
• It is necessary to standardize number assignment
• Therefore, the current adapted convention is the sn (stereochemical numbering) system.
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Glycerophospholipid
• R1, R2, R3 refers to groups attached at C1, C2,
C3 position, respectively
• R1 and R2 are generally bonded to fatty acyl
groups – forms the hydrophobic part
• R1 & R2 can vary in
• carbon chain length
• saturation
• In phospholipids, R3 contains a phosphate or its
derivative, which makes the hydrophilic part.
• R3 can vary in
• different phosphate derivatives
Glycoglycerolipids
• Glycoglycerolipids are less frequent in animal membranes
• They are widespread in plant (especially chloroplast) and in various microbes
• Glycoglycerolipids have sugar at R3
• Example shown above is monogalactosyl diglyceride, which accounts for about
half lipid in chloroplast membrane
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Sphingolipids
• Sphingolipids is built on amino alcohol sphingosine (rather than glycerol)
• Sphingosine:
• naturally has a hydrophobic tail of 15 carbons
• C=C at the beginning of its hydrophobic tail
• Contains a primary amine ( ‐NH2) at C2
• Contains a primary hydroxyl (‐OH) at C1
• Contains a secondary hydroxyl (‐OH) at C3
3
2
Sphingosine
1
• Because sphingosine already has one tail, it just needs another fatty acid to form the basic
membrane lipid.
• Ceramide ‐ Fatty acid attach to C2 via amide bond.
• Sphingomyelin – further modification of ceramide at C1 with phosphocholine
Sphingomyelin
Ceramide
Glycosphingolipids
• Glycosphingolipids are ceramides + sugars at C1
• Cerebrosides – one sugar attached
• Typically glucose or galactose
• Gangliosides – one or more sialic acid attached
• Different gangliosides differ in position and
number of sialic acid
• These molecules are especially common in
membranes of nerve cells
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Structural comparison between sphingolidpids
http://en.wikipedia.org/wiki/Cerebroside
Cholesterol
• Cholesterol, is a component of many animal membranes.
• It influences membrane fluidity by its bulky structure
Chair form for the rings – rigid structure
When present in membrane, will disrupt hydrophobic tail packing
Cholesterol Membrane fluidity
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Cholesterol
• Cholesterol is precursor to many hormones
(Male sex hormone)
(Female sex hormone)
(immunosuppressant)
(regulate blood pressure)
(immunosuppressant)
(immunosuppressant)
Membranes are dynamic fluids
•
Fluid mosaic model proposed by S. J. Singer and G. L. Nicolson in 1972.
•
A membrane is a fluid mixture of lipids and proteins.
•
Peripheral membrane proteins are associated with one side of the bilayer and can be separated from the membrane without disrupting the bilayer. May or may not be attached to the membrane.
•
Integral membrane proteins are more deeply embedded in the bilayer and can only be extracted under conditions that disrupt membrane structure.
•
Many integral membrane proteins extend through the bilayer.
http://en.citizendium.org/wiki/Cell_membrane
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Membrane components move around
• Membrane proteins and membrane components are
constantly moving around redistributing themselves.
• They move in 2D (lateral diffusion)
What factors affect membrane properties?
• Component of the membrane
• Length of the hydrophobic tail
• Unsaturation of the hydrophobic tail
• Amount of cholesterol
• Temperature
• Cold = stiff
• Hot = fluidly
• Transition temperature of
membrane:
• Temperature which
membrane go from
Gel to semifluid liquid
crystalline
• Biological membrane at
physiological condition is at
semi‐fluid liquid crystalline
state
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Composition of common biological membranes
Lateral vs. transverse movement
Transverse movements
• “flip‐flop” are more difficult (slower)
to occur.
• Typically, this flip‐flop movement is
aided by enzymes
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Asymmetry of membranes
•
The two leaflets of a membrane usually
differ in lipid composition.
•
Lipid composition in the outer leaflet
(green) and inner leaflet (gold) of the
plasma membrane is graphed for three
cell types.
•
•
•
•
•
leaflet
PC phosphatidylcholine
PE phosphatidylethanolamine
PS phosphatidylserine
PI = phosphatidylinositol
SP = sphingomyelin
Peripheral protein
• Peripheral proteins attach to membrane through association
• They are present on one leaflet
Erythrocyte membrane
• Contains few proteins on outside of the cell
• Contains 2D network of actin, band 4.1, and spectrins, on the inside surface of
cell
• The structural network of these proteins provide excellent support for
maintaining its shape
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Integral proteins
• Integral membrane proteins contains hydrophobic residues that promote association with
the hydrophobic tails of membrane
Typical transmembrane domain structures
• Transmembrane domains typically form α‐helices or β‐sheets with hydrophobic residues
α-helices
(bacteria rhodopsin)
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β-barrels
(OmpF porin)
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Integral membrane proteins have transmembrane domains
• The sequence and postulated structure of glycophorin A (protein used to carry sugars, in
particular, sialic acid on red blood cells): • This protein was the first integral membrane protein to be sequenced. The external (N‐
terminal) domain carries 15 O‐linked and one N‐linked oligosaccharides; together these
constitute ~60% of the total protein mass.
o The single transmembrane helix is highly hydrophobic.
o The cytosolic C‐terminal domain is quite hydrophilic.
Copyright © 2013 Pearson
Canada Inc.
10 - 37
Integral membrane proteins have transmembrane domains
Bacteriorhodopsin
‐ an integral membrane protein:
•
A key enzyme for photosynthesis in some
bacteria (not the same found in plants).
•
Functions as a light driven proton pump
•
Seven helices span the membrane
Hydrophobicity plot
Hydrophobic residues
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When inserting proteins into the membrane
Membrane rafts
• Membrane rafts or lipid rafts are
rich in cholesterol, sphingolipids, and
GPI‐linked proteins.
• The bilayer is thicker in rafts than in
the surrounding membrane.
• The proteins coalesce and form
nanometer‐sized dynamic raft
domains, which may be stabilized by
interactions with actin fibers.
• Rafts can associate to form larger
structures (“platforms”).
• Certain proteins interact
preferentially with rafts (orange
shading), while others do not (brown
shading) or are excluded.
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