Biochemistry

Dr. Tareq Alhindi

Lecture Notes (04)

 Amino Acids and Peptides The R group determines the identity of the
particular amino acid

Amino Acids Are Three-Dimensional

Among all the possible amino acids, only 20 are usually found in
proteins.
The general structure of amino acids includes an amino group and a
carboxyl group, both of which are bonded to the α-carbon.
The α-carbon is also bonded to a hydrogen and to the side chain
group, which is represented by the letter R.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional
Such a center occurs in all amino acids except glycine.
One of the most important properties of these
compounds is their three-dimensional shape, or
stereochemistry.
A frequently encountered chiral center in biomolecules
is a carbon atom with four different groups bonded to it.
Glycine has two hydrogen atoms bonded to the α-
carbon; the side chain (R group) of glycine is hydrogen.
Glycine is achiral because of this symmetry.

Amino acids L or D forms terminology comes from the

Latin words laevus and dexter, meaning “left” and
“right”.
Which comes from the ability of optically active
compounds to rotate polarized light to the left or the
right.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

The amino acids that occur in proteins are all of the L

form.
Although D-amino acids occur in nature, most often in
bacterial cell walls and in some antibiotics, they are not
found in proteins.
The R groups, and thus the individual amino acids, are
classified according to several criteria.

- polar or nonpolar
- acidic or basic
- Other functional groups

We can refer to amino acids by three-letter or one-letter

abbreviations of their names, with the one-letter designations
being much more prevalent.
Amino Acids and Peptides
Amino Acids Are Three-Dimensional
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

Amino acids with nonpolar side chains are: glycine, alanine, In phenylalanine, the
valine, leucine, isoleucine, phenylalanine, tryptophan, hydrocarbon group is aromatic (it
methionine and proline. contains a cyclic group similar to
a benzene ring).
Alanine, valine, leucine, and isoleucine; each side chain is an
aliphatic hydrocarbon group.
In tryptophan, the side chain
contains an indole ring, which
Proline has an aliphatic cyclic structure, and the nitrogen is
is also aromatic.
bonded to two carbon atoms. In the terminology of organic
chemistry, the amino group of proline is a secondary amine,
and proline is often called an imino acid. In methionine, the side chain
contains a sulfur atom in addition to
The amino groups of all the aliphatic
other common amino acids hydrocarbon groupings.
are primary amines.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional
Another group of amino acids has polar side chains that The hydroxyl group in tyrosine is bonded to an aromatic
are electrically neutral (uncharged) at neutral pH. This hydrocarbon group, which eventually loses a proton at
group includes serine, threonine, tyrosine, cysteine, higher pH.
glutamine, and asparagine.
The hydroxyl group in tyrosine is a phenol, which is a
In serine and threonine, the polar group is a hydroxyl stronger acid than an aliphatic alcohol. As a result, the side
(OH) bonded to aliphatic hydrocarbon groups. chain of tyrosine can lose a proton in a titration, whereas
those of serine and threonine would require such a high pH
that pK values are not normally listed for these side chains.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

In cysteine, the polar side chain consists of a thiol group (-SH), The amino acids glutamine and asparagine have
which can react with other cysteine thiol groups to form amide groups, which are derived from carboxyl
disulfide (-S-S-) bridges in proteins in an oxidation reaction. groups, in their side chains.
The thiol group can also lose a proton.

Amide bonds do not ionize in the range of pH

usually encountered in biochemistry.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

Two amino acids, glutamic acid and aspartic acid, have Because of the presence of the carboxylate, the side chain of
carboxyl groups in their side chains in addition to the each of these two amino acids is negatively charged at
one present in all amino acids. neutral pH.

A carboxyl group can lose a proton, forming the

corresponding carboxylate anion.
glutamate and aspartate
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

Three amino acids; histidine, lysine, and arginine, have In free histidine, the pKa of the side-chain imidazole group
basic side chains, and the side chain in all three is is 6.0, which is not far from physiological pH. The pKa
positively charged at or near neutral pH. values for amino acids depend on the environment and can
change significantly within the confines of a protein.
In lysine, the side-chain amino group is attached to an
aliphatic hydrocarbon tail.

In arginine, the side-chain basic group, the guanidino group,

is more complex in structure than the amino group, but it is Histidine can be found in the protonated or unprotonated
also bonded to an aliphatic hydrocarbon tail. forms in proteins.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

Many other amino acids, in addition to the ones

listed here, are known to exist. They occur in some,
but by no means all, proteins.

They are derived from the common amino acids

and are produced by modification of the parent
amino acid after the protein is synthesized by the
organism in a process called posttranslational
modification.
Hydroxyproline and hydroxylysine differ from the
parent amino acids in that they have hydroxyl
groups on their side chains; they are found only in a
few connective-tissue proteins, such as collagen.
 Amino Acids and Peptides
Amino Acids Are Three-Dimensional

Thyroxine differs from tyrosine in that it has an extra iodine-

containing aromatic group on the side chain; it is produced only in the
thyroid gland, formed by posttranslational modification of tyrosine
residues in the protein thyroglobulin. Thyroxine is then released as a
hormone by proteolysis of thyroglobulin.
 Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases

In a free amino acid, the carboxyl group and amino A zwitterion has equal positive and negative charges; in
group of the general structure are charged at neutral solution, it is electrically neutral.
pH.
When an amino acid is titrated, its titration curve indicates
the reaction of each functional group with a hydrogen ion.

The distinguishing feature of amino acids are their side

chains or R groups. R groups can be either acidic, basic,
polar or neutral depending on their structure and formula.
Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases The titration curve of alanine is that of a
diprotic acid.
 Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases

In histidine, the imidazole side chain also contributes a titratable group. At very low pH values, the histidine
molecule has a net positive charge of 2 because both the imidazole and amino groups have positive charges.
 Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases
The titration curve of histidine is that of a triprotic acid The titratable groups of each of the amino acids have
characteristic pKa values. The pKa values of -carboxyl
groups are fairly low, around 2.

The pKa values of amino groups are much higher, with

values ranging from 9 to 10.5.

The pKa values of side-chain groups, including side-chain

carboxyl and amino groups, depend on the groups’
chemical nature.
 Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases

The classification of an amino acid as acidic or basic

depends on the pKa of the side chain, as well as the
chemical nature of the group.

Histidine, lysine, and arginine are considered basic

amino acids because each of their side chains has a
nitrogen containing group that can exist in either a
protonated or deprotonated form.

Aspartic acid and glutamic acid are considered acidic

because each has a carboxylic acid side chain with low
pKa value.
 Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases

These groups can still be titrated after the amino acid is

incorporated into a peptide or protein, but the pKa of the
titratable group on the side chain is not necessarily the
same in a protein as it is in a free amino acid. In fact, it can
be very different. For example, a pKa of 9 has been
Serum protein electrophoresis
reported for an aspartate side chain in the protein
thioredoxin.
Amino acids, peptides, and proteins have different pKa
values, giving the possibility that they can have different
charges at a given pH.

This property is useful in a number of laboratory

techniques such as electrophoresis and chromatography.
Ion Exchange Chromatography
 Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases

The pH at which a molecule has no net charge is called

the isoelectric pH, or isoelectric point (given the symbol
pI).
At its isoelectric pH, a molecule will not migrate in an
electric field.

The pI of an amino acid can be calculated by the following

equation:
Amino Acids and Peptides
Amino Acids Can Act as Both Acids and Bases
 Amino Acids and Peptides
The Peptide Bond

Individual amino acids can be linked by forming Peptides are compounds formed by linking small numbers
covalent bonds. of amino acids, ranging from two to several dozen. In a
The bond is formed between the α-carboxyl group of protein, many amino acids (usually more than a hundred)
one amino acid and the α -amino group of the next are linked by peptide bonds to form a polypeptide chain.
one.
Another name for a compound formed by the reaction
between an amino group and a carboxyl group is an
amide.

The carbon–nitrogen bond formed when two amino acids

are linked in a peptide bond is usually written as a single
bond.
 Amino Acids and Peptides
The Peptide Bond

A simple shift in the position of a pair of electrons, it is The peptide bond can be written as a resonance hybrid of two
quite possible to write this bond as a double bond. structures.

This shifting of electrons is well known in organic

chemistry and results in resonance structures,
structures that differ from one another only in the
positioning of electrons.

All resonance structures contribute to the bonding

situation.

The peptide bond has partial double bond character. As a

result, the peptide group that forms the link between the two
amino acids is planar. Also, it is stronger than an ordinary single
bond because of this resonance stabilization.
Benzene
 Amino Acids and Peptides
The Peptide Bond
This stereochemical constraint plays an important role
This structural feature has important implications for the in determining how the protein backbone can fold.
three-dimensional conformations of peptides and proteins.

There is free rotation around the bonds between the α-

carbon of a given amino acid residue and the amino nitrogen
and carbonyl carbon of that residue, but there is no
significant rotation around the peptide bond.
 Amino Acids and Peptides
The Peptide Bond

What are some biological functions of small peptides?

One of the most important of these roles is that of

hormones.
Some important peptide hormones have cyclic structures, as in oxytocin and
vasopressin.

In each, there is an –S-S- bond responsible for the cyclic structure. Each of
these peptides contains nine amino acid residues, each has an amide group
(rather than a free carboxyl group) at the C-terminal end, and each has a
disulfide link between cysteine residues at positions 1 and 6.
Amino Acids and Peptides
The Peptide Bond