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Biochemistry of Biomolecules
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BIOCHEMISTRY OF BIOMOLECULES
Chapter 6: Lipids and Membranes
Subtopic:
6.1 Membranes
1. The membrane is made by two layers of lipid molecules and this is known as the lipid
bilayer. The lipid molecules of membrane have smooth hydrophilic heads and long chains
in the hydrophobic tail portion.
2. The physical properties of lipid in aqueous solution cause them to aggregate.
 Water tends to exclude the hydrophobic portions of amphiphilic lipids, whereas the
polar head groups remain in contact with the aqueous environment.
 A single tailed lipid molecule contains a tapered van der Waal’s envelope. An optimum
number of these lipid molecules form a sphere, called micelle.
 Too few lipid molecules would expose the hydrophobic core of the micelle to water,
whereas too many would give the micelle an energetically unfavourable hollow
center.
 The system will try to push out the water and extra lipid molecules to return back to
the stable conformation. This means that a large micelle could flatten out to
eliminate this hollow center, but resulting decrease of curvature at the flattened
surfaces would also generate empty spaces.
 A double tailed lipid molecule has a cylindrical van der Waal’s envelope. A collection of
these double tailed lipid molecules will also form a micelle.
 The central region of the micelle will form a lipid bilayer.
 An extended flat arrangement of such double tailed lipid molecules represents
membrane.
3. The transfer of a lipid molecule across a lipid bilayer is known as transverse diffusion or
flip-flop is an extremely rare event. This is because the passage of a polar head group
through the hydrophobic interior of the bilayer is thermodynamically unfavourable.
4. In lateral diffusion, lipids are highly mobile in the plane of the bilayer. This indicates that
the hydrocarbon core of the bilayer is highly fluid. The motion of the acyl chains is greatest
in the center of the bilayer and decreases markedly near the polar head groups.
5. Living organisms alter their membrane composition in order to maintain constant fluidity
as the ambient temperature varies.
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6. Bilayer fluidity is a function of temperature. The transition temperature, the temperature
at which the phase changes, increases with the chain length and the degree of saturation
of its component fatty acid residues.
 Above the transition temperature, the highly mobile lipids are in a state known as a
liquid crystal because they are ordered in some directions but not in others.
 Below the transition temperature, the lipid molecules form a much more orderly array
to yield a gel-like solid. The bilayer is thicker in the gel state than in the liquid crystal
state due to the stiffening of the hydrocarbon tails at lower temperatures.
 The presence of cholesterol also reduces a bilayer’s transition temperature. It also
broadens the temperature range of the phase transition.
 At moderately warm temperatures, the cholesterol molecules reduce membrane
fluidity by preventing free movement of phospholipid molecules.
 At low temperatures, the cholesterol molecules prevent close packing of
phospholipids and slow down solidification.
7. Functions of membrane:
 Delineation and compartmentalization
 Membranes enable separate compartments to be formed within a cell in which
specific biochemical pathways can occur.
 Membrane acts as a barrier for hydrophilic molecules.
 Membrane keeps essential substances inside the cell and keeps the undesirable
substances out.
 Organization and localization of function
 Inner membrane of mitochondrion: role in respiration
 Thylakoid membrane of chloroplast: role in photosynthesis
 Endoplasmic reticulum: site of synthesis of biomolecules (proteins, lipids)
 Transport
 Membranes are selectively permeable and regulate movement of substances in and
out of the cell.
 Cell to cell communication
 Cells in a tissue bind and align to each other through membrane proteins and
interact with each other.
 In animal cells: gap junctions
 In plant cells: plasmodesmata
 Signal detection
 Membrane proteins act as antenna to receive ligands to communicate with the
surrounding and initiate a biochemical reaction inside the cell.
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8. Fluid mosaic model of membrane
 Fluid: Lipid components are in constant motion, capable of lateral diffusion.
 Mosaic: Proteins embedded in lipid bilayer.
 There is freedom of motion of membrane components, especially lipid molecules and
some proteins.
 Chain length, degree of unsaturation of fatty acids and amount of cholesterol present
affect the membrane fluidity.
 Some organisms compensate for temperature changes through lipid composition
alteration, known as homeoviscous adaptation.

 The validity of this model was demonstrated by the cell fusion experiment.
 A mouse cell was first treated with antibodies that were specific for the membrane
proteins of the cell. To the antibodies, a fluorescent dye, say red, was attached.
 Similarly, a human cell was prepared but with a green dye.
 These two cells were made to fuse using the membrane encapsulated Sendai virus.
 Even though initially the two colours were observed only on the respective cell
region, the dyes diffused throughout the fused cell after some time demonstrate
that the attached protein could freely move in the membrane.
9. Membrane proteins
 Membrane proteins may move laterally and some may be restricted if they are
anchored to the cytoskeleton.
 Peripheral proteins (extrinsic proteins)
 These proteins occur on the surface of the phospholipid bilayer and they bound to
membranes by hydrophilic bonds. They do not have discrete hydrophobic
sequences.
 They are easily dislodged from the membrane by relatively gentle extraction
procedures as they have weak interaction with membrane.
 Integral proteins (intrinsic proteins)
 These proteins penetrate only part of their way into or all the way through the
phospholipid bilayer. Some proteins, known as transmembrane proteins, span the
membrane. The number of segments and orientation vary according to function.
Bacteriorhodopsin is an all helical membrane protein.
 These proteins maintain their position in the cell membrane by hydrophobic and
hydrophilic bond. The hydrophobic regions are with affinity for the interior of the
lipid bilayer while the hydrophilic regions extend outward to the aqueous
environment.
 They are not easily to be removed.
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10. The hydropath plot of a protein identifies the hydrophobic and hydrophilic regions of the
protein. Each amino acid has a hydropathy index.
 The cumulative sum of hydropathy indices (for say 10 amino acids) is plotted against 1,
for amino acids 2 to 11 against 2 and so on.
 The reason to take a window of 10 amino acids is to accept the fact that we want to
know a hydrophobic or hydrophilic regions in a protein and not how each amino acid in
a region behaves.
11. The erythrocyte is one of the well studied membrane systems.
 The erythrocytes have no organelles and minimum function. Their’s biconcave disklike
shape, which is essential for its O2 carrying properties, is maintained by the membrane
skeleton, a network of proteins located just beneath the membrane.
 The blood group are marked by the presence of A, B antigens (components of
erythrocytes surface sphingoglycolipids), both antigens or no antigen, respectively.
12. Cell to cell transport
 Material transport between two cells is important for the growth of tissue or an
organism. The major mode is gap junction.
 The gap junction is a physical conduit like passage formed by membrane.
 Small molecules like nucleotides, amino acids, ions and sugars travel very easily across
the gap junction and big molecules like proteins and nucleic acids cannot travel through
the gap junction.
 The equivalent structure in plants is known as plasmodesmata.
13. Within the cell transport
 Vesicles
 The molecules that are to be transported into a cell lie first on the surface of a cell.
 The membranous region on the cell invaginates and forms a pouch, known as vesicle,
and detaches from the cell surface.
 The vesicle travels to the destination and fuses with the destination organelle.
 Signal peptide
 Some proteins are transported to their destination with the help of a specialized
protein sequence called signal peptide, attached to the protein.
 The protein is first delivered to their destination and the signal peptide is mostly
cleaved from the main protein.
 The signal peptide can have a minimum length of even 3 amino acids and up to 30
amino acids. It can be present at the N-terminus or the C-terminus.
 Clathrin coated vesicle
 In some cases, a vesicle is further protected by a cage made by clathrin, which is a
small protein.
 A triangular assembly three clathrin protein molecules is first made. This assembly
extends to make a full net.
14. Cell to surrounding transport
Energy from ATP Protein molecule
Simple Diffusion
X
X
Facilitated Diffusion
X
√
Active transport
√
√
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15. Simple diffusion
 Simple diffusion is defined as the net movement of ions or molecules down a
concentration gradient.
 The phospholipid bilayer is permeable to very small uncharged molecules like oxygen
and carbon dioxide. Hydrophobic substances, for example, steroids can also diffuse
through.
 The phospholipid bilayer is not permeable to charged ions and hydrophilic molecules
like glucose and macromolecules.
 The Fick’s law of diffusion determines how different molecules with different levels of
polar nature diffuse across a water-oil partition.
16. Facilitated diffusion
 Charged particles and hydrophilic molecules do not readily pass through the plasma
membrane because they are relatively insoluble in lipids. In plasma membrane, certain
proteins assist such particles to diffuse into or out of the cell. This process is called
facilitated diffusion.
 Facilitated diffusion via channel protein
 The channel protein forms a solute specific hydrophilic channel for transportation
through membrane.
 Example: Gramicidin A, which permits protons and alkali cations to pass through
membrane. Even though the side chains of Gramicidin A are hydrophobic, the inner
coat of the helix is hydrophilic.
 Facilitated diffusion via carrier protein
 The carrier protein physically collects the cargo molecules at the surface of the
membrane and travels to the other side.
 The polar groups of the solute are shielded from the non-polar interior of the
membrane.
 An example is how valinomycin transports potassium ion into a cell. Valinomycin is a
small peptide that binds to the potassium ion, physically travels to the cytoplasm
and delivers at the other side.

As a special case, the human erythrocyte transporter protein, GLUT1 transports
glucose across the erythrocyte membrane by means of conformational change.
 Glucose binds to the protein on one face of the membrane.
 A conformational change closes the first binding site and exposes the binding site on
the other side of the membrane (transport).
 Glucose dissociates from the protein.
 The transport cycle is completed by the reversion of GLUT1 to its initial
conformation in the absence of bound glucose (recovery)
17.
Active transport

Active transport is defined as the movement of ions or molecules across a
membrane against a concentration gradient by means of specific transport proteins
and with the expenditure of energy by the cell.

Several types of membrane proteins are involved in active transport:
 Uniport carriers carry a single ion or molecule in a single direction.
 Symport carriers carry two substances in same direction.
 Antiport carriers carry two substances in opposite direction.
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Case study: Na-K ATPase (pump)
Sodium-potassium ATPase uses the energy generated by the hydrolysis of ATP in
transporting Na out and K into a cell in the antiport mode. It has two subunits:
110 kD α subunit that contains catalytic activity
55 kD β subunit
ATP is hydrolysed and the binding of the phosphate group to the protein pump
changes the protein conformation.
It actively transports 3 sodium ions out of the cell for every 2 potassium ions
pumped against their concentration gradient into the cell.
Phosphate leaves the protein and K+ are released inside.
The electrochemical gradient created by the Na-K pump is responsible for the
electrical excitability of nerve cells
Similar to the Na-K pump, other pumps like Ca pump and H-K pump are exist as well.
Case study: Transportation of glucose from intestine to muscle
 Glucose from the intestine side is first transported to the epithelial cell by the NaGlucose symport pump.
 Glucose is further transported to the blood stream by the glucose uniport pump.
 The accumulated Na in the epithelial cell is brought back to the intestine by the Na-K
antiport pump.
 In the blood stream, glucose is transported into the erythrocyte cell by GLUT1 and
taken to muscle cells and delivered.