Molecular Cell Biology –Chapter 2 Résumé
Many biomolecules dissolve in water. Those molecules are called hydrophilic (1). Some are oily,
fatlike substances that shun water, they are hydrophobic (2). There are also “schizophrenic”
biomolecules that contain both hydrophilic and hydrophobic regions. They are said to be
amphipathic (3).
Hydrophilic
Hydrophobic
Amphipathic
Dissolve in water
Avoid water
Contain both hydrophilic and hydrophobic
regions.
2.1 : Covalent bonds and noncovalent
interactions (LECTURE 1)
Strong forces form a covalent bond when two atoms share one pair of electrons (single bond) or
multiple pairs of electrons (double, triple, etc.). The weak attractive forces of noncovalent
interactions are equally important in determining the properties and functions of biomolecules
such as proteins, nucleic acids, carbohydrates and lipids.
The electronic structure of an atom determines the number and geometry of covalent bonds it
can make.
Some atoms readily form covalent bonds, using electrons in the outermost electron orbitals
surrounding their nuclei. All the biological bulding blocks are organized around the carbon atom.
The tetrahedral orientation of bonds formed by an asymmetric carbon atom can be arranged in
3D space in two different ways, producing molecules that are mirror images of each other. This
propriety is called chirality. Such molecules are called stereoisomers. The different
stereoisomers of a molecule have different biological activities.
Electrons may be shared equally or unequally in covalent bonds.
The extent of an atom’s ability to attract an electron is electronegativity. In a bond in which
atoms have similar electronegativities, the electrons that are bonded are shared equally. Such
bonds are called non-polar. Some molecules have bonded atoms with different
electronegativities. The bond between those atoms is said to be polar : one end of a polar bond
has a partial negative charge. The other end has a partial positive charge.
The polarity results in a resonance hybrid, a structure between two forms shown in Chap.2 page
34.
Covalent bonds are much stronger and more stable than noncovalent interactions.
Covalent bonds are very stable because the energies required to break them are much greater
than the thermal energy available at room temperature. In comparison, the energy required to
break noncovalent interaction is much less. They are weak enough to be constantly being
formed and broken at room temperature. However, multiple noncovalent interactions can act
together to produce stable and specific associations.
Ionic interactions are attractions between oppositely charged ions.
Ionic interactions result from the attraction of a positively charged ion (cation) for a negatively
charged ion (anion). Ionic interactions have no specific geometric orientation. In fact, the
electrostatic field around an ion is uniform in all directions. Most ionic compounds dissolve
readily in water because the energy of hydration (energy released when ions tightly bind water
molecules) is greater than the lattice energy that stabilizes the crystal structure.
The relative strength of the interaction between two ions depends on the concentration of
other ions in a solution. The higher the concentration of other ions, the more opportunities the
anion and the cation have to interact ionically with these other ions. Thus, the lower the energy
required to break the interaction between the anion and the cation.
Hydrogen bonds determine the water solubility of uncharged molecules.
A hydrogen bond is the interaction of a partially positively charged hydrogen atom in a
molecular dipole with unpaired electrons from another atom in the same or different molecule.
A hydrogen atom can form, in addition to its covalent bond, a weak association with an acceptor
atom A, which must have a nonbonding pair of electrons available for the interaction.
An important feature of all hydrogen bonds is directionality. In the strongest hydrogen bonds,
the donor atom, the hydrogen atom and the acceptor atom all lie in a straight line. Non-linear
hydrogen bonds are weaker than linear ones. Hydrogen bonds are both longer and weaker than
covalent bonds between the same atoms.
Van der Waals interactions are caused by transient dipoles.
When two atoms approach each other closely, they create a weak force called a vdW
interaction. These interactions result from the momentary random fluctuations in the
distribution of the electrons of any atome, which give rise to a transient unequal distribution of
electrons. If two atoms are close enough together, electrons of one atom will perturb the
electrons of the other. This perturbation generates a transient dipole in the second atom, and
the two dipoles will attract each other weakly. VdW interactions are responsible for the
cohesion between nonpolar molecules like heptanes.
Their strength decreases with increasing distance. If the atoms get too close together, however,
they become repelled by the negative charges of their electrons. The strength of the vdW
interaction is 1kcal/mol, weaker than hydrogen bonds.
The hydrophobic effect causes nonpolar molecules to adhere to one another.
Hydrocarbons (made of C and H) are virtually insoluble in water. After being shaken in water,
triacylglycerols form a separate phase. Nonpolar molecules tend to aggregate in water. This is
the hydrophobic effect. Because water molecules cannot form hydrogen bonds with nonpolar
substances, they tend to form cages around them. This state is energetically unfavourable
because it decreases the randomness of the population of water molecules.
If nonpolar molecules aggregate with their hydrophobic surfaces facing each other, the
hydrophobic surface area exposed to water is reduced. As a consequence, less water is needed
to form the cages surrounding the nonpolar molecules, and entropy increases. The hydrophobic
effect results from an avoidance of an unstable state.
Nonpolar molecules can also associate through vdW interactions. The net result of the
hydrophobic and van der Waals interactions is a very powerful tendency for hydrophobic
molecules to interact with one another, not with water.
Molecular complementarity mediated via noncovalent interactions permit tight, highly
specific binding of biomolecules.
When two molecules encounter each other, they most likely will simply bounce apart because
the noncovalent interactions that would bind them together are weak and have a transient
existence at physiological temperature. However, molecules that exhibit a lock-and-key kind of
fit between their shapes, charges, etc. can form multiple non-covalent interactions at close
range.
The higher the affinity of two molecules for each other, the better the molecular fit between
them, the more non-covalent interactions can form and the tighter they can bind.
Covalent
Ionic
Hydrogen
Van der Waals
Hydrophobic
Polar : one end of a polar bond has a partial negative charge.
The other end has a partial positive charge.
Nonpolar : Similar electronegativities.
Ionic interactions result from the attraction of a positively
charged ion (cation) for a negatively charged ion (anion). The
strength of this binding depends on the concentration of other
ions in the solution.
A hydrogen bond is the interaction of a partially positively
charged hydrogen atom in a molecular dipole with unpaired
electrons from another atom in the same or different molecule.
Strongest hydrogen bonds are linear.
When two atoms are close enough together, electrons of one
atom will perturb the electrons of the other. This perturbation
generates a transient dipole in the second atom, and the two
dipoles will attract each other weakly.
If nonpolar molecules aggregate with their hydrophobic
surfaces facing each other, the hydrophobic surface area
exposed to water is reduced. As a consequence, less water is
needed to form the cages surrounding the nonpolar molecules,
and entropy increases. The hydrophobic effect results from an
avoidance of an unstable state.
2.2 Chemical Building Blocks of Cells
(LECTURE 2)
The three most abundant classes of the critically important biological macromolecules (proteins,
polysaccharides and nucleic acids) are all polymers composed of multiple covalently linked
building block small molecules, called monomers.
Proteins are linear polymers containing amino acids (10-thousands) linked by peptide bonds.
Nucleic acids are linear polymers containing nucleotides (hundreds to millions) linked by
phosphodiester bonds.
Polysaccharides are linear or branched polymers of sugars linked by glycosidic bonds.
The formation of a covalent bond between two monomer molecules includes the loss of a H
from one monomer and a hydroxyl (OH) from the other monomer. This is called a dehydration
reaction. Macromolecular structures can also be assembled with noncovalent interactions. The
two-layered structure of cellular membranes is built by the n-cov assembly of phospholipids.
Amino acids differing only in their side chains compose
proteins.
The monomeric building blocks of proteins are 20 amino
acids. All amino acids have a characteristic structure
consisting of a central alpha carbon atom bonded to four
different chemical groups : (1)an amino group, (2)a
carboxylic acid or carboxyl group, (3)a hydrogen atom and
a (4) side chain or R group. These molecules exist in
dextro and levo stereoisomers. Only the L forms are
found in proteins.
Amino acids with nonpolar side chains are hydrophobic and so poorly soluble in water. The
larger the nonpolar side chain, the more hydrophobic the aminoacid. Amino acids with polar
side chains are hydrophilic. The most hydrophilic of these amino acids is the subsets with side
chains that are charged at the pH typical of biological fluids (around 7). Negative charges are
associated with acids.
Regions within a single protein chain or separate chains are sometimes cross-linked through
disulfide bonds. Those bonds stabilize the folded structure of some proteins. Although cells use
the 20 amino acids shown in the INITIAL synthesis of proteins, analysis of cellular proteins
reveals that they contain upward of 100 different ones! Chemical modifications account for this
difference. Acetyl groups and a variety of other chemical groups can be added to specific
internal amino acids after they are incorporated into proteins. Acetylation (addition of an acetyl
to the amino group of the N-terminal residue) is the most common form of amino acid chemical
modification.
Five different nucleotides are used to build nucleic acids
Two types of chemically similar nucleic acids, DNA and
RNA, are the principal genetic information carriers of the
cell. The monomers from which they are built , called
nucleotides, have a common structure:
1. A phosphate group linked by a phosphoester
bond to a
2. Pentose (5-carbon sugar molecule) linked to a
3. Base (nitrogen and carbon-containing ring
structure)
In RNA, the pentose is ribose; in DNA, the pentose is deoxyribose. As for the bases, thymine is
only found in DNA, and uracil is found only in RNA.
Adenine and guanine are purins, which contain a pair of fused rings. Cytosine, thymine and
uracil are pyrimidines, containing a single ring. The acidic character of nucleotides is due to the
phosphate group, which under normal intracellular conditions releases hydrogen ions. Most
nucleic acids in cells are associated with proteins, which form ionic interactions with the
negatively charged phosphates.
Cells and extracellular fluids in organisms contain small concentrations of nucleosides (base +
sugar, no phosphate). The nucleosides triphosphates are used in the synthesis of nucleic acids.
GTP participates in intracellular signalling and acts as an energy reservoir (protein synthesis) and
ATP is the most widely used biological energy carrier.
Monosaccharides joined by glycosidic bonds form linear and branched polysaccharides
The building blocks of the polysaccharides are the simple sugars, or monosaccharides. They are
carbohydrates (CH2O)n. All of them contain hydroxyl groups and either an aldehyde or a keto
group.
D-Glucose (C6) is the principal external source of energy for most cells and can exist in three
forms: one linear structure and two different hemiacetal ring structures. The pyranose form is
the most abundant. Its most stable conformation is a chairlike shape.
Disaccharides are the simplest polysaccharides. The most common storage carbohydrate in
animal cells is glycogen (very long, highly branched). In plant cells, it is starch, a glucose polymer.
Both glycogen and starch are composed of the alpha anomer of clucose. Cellulose, the major
constituent of plant cell walls, is an unbranched polymer of the beta anomer of glucose.
Any two sugar molecules can be linked in a variety of ways because each monosaccharide has
multiple hydroxyl groups that can participate. Any mone monosaccharide has the potential of
being linked to more than two other monosaccharides, thus generating a branch point and nonlinear polymers.
Phospholipids associate noncovalently to form the basic bilayer structure of biomembranes
Membranes define what is a cell and what is not. They are assembled by the noncovalent
association of their component building blocks. The primary building blocks of all biomembranes
are phospholipids.
Phospholipids consist of two long-chain, nonpolar fatty acid groups linked to small, highly polar
groups (including a phosphate and a short organic molecule).
Fatty acids consist of a hydrocarbon chain attached to a carboxyl group. Like glucose, fatty acids
are an energy source for cells. Fatty acids with no carbon-carbon double bonds are said to be
saturated; those with at least one double bond are unsaturated.
Two stereoisomeric configurations, cis and trans, are possible around each c=c bond. In general,
the unsaturated fatty acids in biological systems contain only cis double bonds. The trans fatty
acids are not natural, arising from the catalytic process used for hydrogenation. Saturated and
trans fatty acids have similar properties. They can be covalently attached to another molecule
by esterification (loss of OH in the fatty acid, loss of H from the other molecule’s hydroxyl
group).