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Organic chemistry and Biological chemistry for Health Sciences
59-191
Lecture 17
PROTEINS:
Proteins consist of polypeptide units. Polypeptides are made from -amino acids. A set of
twenty amino acids called standard amino acids is used by all species of plants and
animals. Hundreds of amino acid residues sometimes called peptide units, are joined in a
single polypeptide molecule.
In the solid state amino acids exist entirely in the dipolar form callled zwitterion. Amino
acids are internally neutralized molecule. Since amino acids has its own proton donating
group, NH3+and has its own proton accepting group, COO- so these dipolar ions can
neutralize acids or bases of sufficient strength, like H3O+ and OH-. Because polypeptides
have at least one NH3+ group and one acid neutralizing COO- group, proteins are able to
serve as buffers in body fluids.
At pH 6 to 7 amino acids exist in zwitterion form. At much lower pH (about 1) the COOgroup will accept H+ and change to COOH group. So it will have net positive charge and
can migrate to a negative electrode (cathode) in an electrolysis experiment. On the other
hand at higher pH (about 11) , the OH- take H+ ion from NH3+ groups. So it will have a
net negative charge and migrate to a positive electrode (anode).
The pH at which no net migration of an amino acid occurs in an electrical field is called
the isoelectric point of the amino acid. The symbol of this pH value is pI.
All proteins have NH3+ and COO- group or can acquire them by a change in the pH of the
surrounding medium. So whole protein molecule can have isoelectric point. Each protein
has its own characteristic isoelectric point.
Changing the pH of the surrounding medium can alter the entire electrical condition of
the huge protein molecules. Such changes in the electrical charge of a protein have
serious consequences in the molecular level of life. Change of electrical charge also
greatly alters the protein solubility. If proteins are to serve their biological purpose, some
must not be allowed to go into solution and others must not be permitted to precipitate.
So it is very important for an organism to control the pH values of its fluids.
Amino acids can be grouped together based on the properties of their R groups (side
chains).
Hydrophobic side chains:
The hydrocarbon R groups in this class of amino acids are nonpolar and hydrophobic.
When a long polypeptide molecule folds into its distinctive shape, these hydrophobic
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groups tend to be folded next to each other as much as possible rather than next to highly
polar groups or water molecules. Water avoidance by nonpolar side chains is called
hydrophobic interactions. So these hydrophobic side chains are important in promoting
hydrophobic interactions within protein structures.
Side chain with hydrophilic OH groups:
These amino acids are polar and hydrophilic. They can both donate and accept hydrogen
bonds. In the folded polypeptide chain side chains with OH groups stick out in the
surrounding aqueous phase to form hydrogen bond.
Carboxyl containing side chain:
Two amino acids aspartic acid and glutamic acid have proton donating COOH group in
the side chain. They mainly exist in their anionic form because body fluid is slightly
basic. To get the protonated form the pH has to be much lowered. This is why the pI
values of aspartic and glutamic acid are much lower (more acidic) than the pI values of
amino acids with non-polar side chains.
Aspargine and glutamine are amides of aspartic acid and glutamic acid respectively, to
which aspargine and glutamine are easily hydrolyzed by acid or base. These are also
polar and hydrophilic groups but they are not electrically charged. They are neither
proton donors nor proton acceptors, so the pI values of aspargine and glutamine are
higher than those of aspartic or glutamic acids.
Side chains with basic groups:
Lysine, arginine and histidine belong to this group. The extra NH2 group of lysine makes
its side chain basic and hydrophilic. Amines in water makes the pH of the solution greater
than 7 because of the presence of OH- ion in the following equilibrium.
RNH2(aq) + H2O
RNH3+(aq) + OH- (aq)
Arginine and histidine have similarly basic side chains.
Sulfur containing side chains:
The side chain in cysteine has an –SH group. Molecules with this group are easily
oxidized to disulfides and disulfides are easily reduced back to –SH groups.
(oxidation)
2RSH
RSSR + H2O
(reduction)
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All of the amino acids except glycine are chiral molecules and can exist as a pair of
enantiomers. All naturally occuring amino acids belong to the L-family. All proteins
in our bodies including all enzymes are made from L-amino acids and they are all chiral
molecules.
STRUCTURE OF PROTEIN:
Protein structure can be considered in four levels. The first and most fundamental level of
protein structure, the primary structure includes all the covalent bonds between all
amino acids and is normally defined by the sequence of peptide bonded amino acids.
Secondary structure is the particular way in which polypeptide chains coil, intertwine or
line up side by side. It entails non-covalent forces, particularly the hydrogen bond.
The tertiary structures of proteins concern further coiling, bending, kinking or twisting
of secondary structure. Mainly non-covalent forces like hydrogen bonds and hydrophobic
interactions stabilize tertiary structure of protein. In many polypeptides electrostatic
interaction between electrically charged side chains of amino acids are also involved in
determining the overall shape of the protein. Sometimes polypeptides have disulfide bond
formed from –SH groups.
Some proteins have quarternary structure. It develops by coming together two or more
polypeptides, often with rather relatively small molecules or ions that aggregate at a
certain manner to form one grand whole.
Primary structure of protein:
The peptide bond is the covalent bond that forms when amino acids are put together to
form polypeptide.
The product of the union of any two amino acid residues by a peptide bond is called a
dipeptide.
Polypeptide structure can be written simply by using three letter symbols for amino acids.
A series of three letter symbols, each separated by a hyphen, may represent a polypeptide
structure, provided that the first symbol is the free amino end NH3+, and the last symbol
is the free carboxylate end –COO-.
Dipeptides still have NH3+ and -COO- group, so a third amino acid can react at either end
to form a tripeptide. This would still have the end groups from which the chain can be
extended further. A repetition of this pattern many hundreds of times would produce a
long polymer, namely a polypeptide.
All polypeptides have same backbone skeletons. They differ in length and in the kinds
and sequences of side chains.