Chemical Nature of the Amino Acids
All peptides and polypeptides are polymers of alpha-amino acids. There are
20 a-amino acids that are relevant to the make-up
of mammalian proteins (see below). Several other amino acids are found in the
body free or in combined states (i.e. not associated with peptides or proteins).
These non-protein associated amino acids perform specialized functions. Several
of the amino acids found in proteins also serve functions distinct from the
formation of peptides and proteins, e.g., tyrosine in the formation of thyroid
hormones or glutamate acting as a neurotransmitter.
The a-amino acids in peptides and proteins
(excluding proline) consist of a carboxylic acid (-COOH) and an amino (-NH2) functional group attached to the same
tetrahedral carbon atom. This carbon is the a-carbon.
Distinct R-groups, that distinguish one amino acid from another, also are
attached to the alpha-carbon (except in the case of glycine where the R-group is
hydrogen). The fourth substitution on the tetrahedral a-carbon of amino acids is hydrogen.
Table of a-Amino Acids Found in Proteins
| Amino
Acid |
Symbol |
Structure* |
pK1 |
pK2 |
pK of
R
Group |
Amino Acids
with Aliphatic R-Groups
|
| Glycine |
Gly - G |
 |
2.4 |
9.8 |
|
| Alanine |
Ala - A |
 |
2.4 |
9.9 |
|
| Valine |
Val - V |
 |
2.2 |
9.7 |
|
| Leucine |
Leu - L |
 |
2.3 |
9.7 |
|
| Isoleucine |
Ile - I |
 |
2.3 |
9.8 |
|
| Non-Aromatic
Amino Acids with Hydroxyl R-Groups |
| Serine |
Ser - S |
 |
2.2 |
9.2 |
~13 |
| Threonine |
Thr - T |
 |
2.1 |
9.1 |
~13 |
| Amino Acids
with Sulfur-Containing R-Groups |
| Cysteine |
Cys - C |
 |
1.9 |
10.8 |
>8.3 |
| Methionine |
Met-M |
 |
2.1 |
9.3 |
|
| Acidic Amino
Acids and their Amides |
| Aspartic Acid |
Asp - D |
 |
2.0 |
9.9 |
3.9 |
| Asparagine |
Asn - N |
 |
2.1 |
8.8 |
|
| Glutamic Acid |
Glu - E |
 |
2.1 |
9.5 |
4.1 |
| Glutamine |
Gln - Q |
 |
2.2 |
9.1 |
|
| Basic Amino
Acids |
| Arginine |
Arg - R |
 |
1.8 |
>9.0 |
12.5 |
| Lysine |
Lys - K |
| 2.2 |
9.2 |
10.8 |
| Histidine |
His - H |
 |
1.8 |
9.2 |
6.0 |
| Amino Acids
with Aromatic Rings |
| Phenylalanine |
Phe - F |
 |
2.2 |
9.2 |
|
| Tyrosine |
Tyr - Y |
 |
2.2 |
9.1 |
10.1 |
| Tryptophan |
Trp-W |
 |
2.4 |
9.4 |
|
| Imino
Acids |
| Proline |
Pro - P |
 |
2.0 |
10.6 |
|
*Backbone of the amino acids is red, R-groups are blue
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Amino Acid Classifications
Each of the 20 a-amino acids found in proteins can
be distinguished by the R-group substitution on the a-carbon atom. There are two broad classes of amino acids
based upon whether the R-group is hydrophobic or hydrophilic.
The hydrophobic amino acids tend to repel the aqueous environment and,
therefore, reside predominantly in the interior of proteins. This class of amino
acids does not ionize nor participate in the formation of H-bonds. The
hydrophilic amino acids tend to interact with the aqeuous environment, are often
involved in the formation of H-bonds and are predominantly found on the exterior
surfaces proteins or in the reactive centers of enzymes.
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Acid-Base Properties of the Amino Acids
The a-COOH and a-NH2 groups in amino acids are capable of
ionizing (as are the acidic and basic R-groups of the amino acids). As a result
of their ionizability the following ionic equilibrium reactions may be written:
R-COOH <--------> R-COO- + H+
R-NH3+ <---------> R-NH2 +
H+
The equilibrium reactions, as written, demonstrate that amino acids contain
at least two weakly acidic groups. However, the carboxyl group is a far stronger
acid than the amino group. At physiological pH (around 7.4) the carboxyl group
will be unprotonated and the amino group will be protonated. An amino acid with
no ionizable R-group would be electrically neutral at this pH. This species is
termed a zwitterion.
Like typical organic acids, the acidic strength of the carboxyl, amino and
ionizable R-groups in amino acids can be defined by the association constant,
Ka or more commonly the negative logrithm of Ka, the
pKa. The net charge (the algebraic sum
of all the charged groups present) of any amino acid, peptide or protein, will
depend upon the pH of the surrounding aqueous environment. As the pH of a
solution of an amino acid or protein changes so too does the net charge. This
phenomenon can be observed during the titration of any amino acid or protein.
When the net charge of an amino acid or protein is zero the pH will be
equivalent to the isoelectric point: pI.
 |
| Titration
curve for Alanine |
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Functional Significance of Amino Acid R-Groups
In solution it is the nature of the amino acid R-groups that dictate
structure-function relationships of peptides and proteins. The hydrophobic amino
acids will generally be encountered in the interior of proteins shielded from
direct contact with water. Conversely, the hydrophilic amino acids are generally
found on the exterior of proteins as well as in the active centers of
enzymatically active proteins. Indeed, it is the very nature of certain amino
acid R-groups that allow enzyme reactions to occur.
The imidazole ring of histidine allows it to act as either a proton donor or
acceptor at physiological pH. Hence, it is frequently found in the reactive
center of enzymes. Equally important is the ability of histidines in hemoglobin
to buffer the H+ ions from carbonic acid ionization in red blood
cells. It is this property of hemoglobin that allows it to exchange
O2 and CO2 at the tissues or lungs, respectively.
The primary alcohol of serine and threonine as well as the thiol (-SH) of
cysteine allow these amino acids to act as nucleophiles during enzymatic
catalysis. Additionally, the thiol of cysteine is able to form a disulfide bond
with other cysteines:
Cysteine-SH + HS-Cysteine <-------->
Cysteine-S-S-Cysteine
This simple disulfide is identified as cystine. The formation of disulfide
bonds between cysteines present within proteins is important to the formation of
active structural domains in a large number of proteins. Disulfide bonding
between cysteines in different polypeptide chains of oligomeric proteins plays a
crucial role in ordering the structure of complex proteins, e.g. the insulin
receptor.
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Optical Properties of the Amino Acids
A tetrahedral carbon atom with 4 distinct constituents is said to be
chiral. The one amino acid not exhibiting
chirality is glycine since its '"R-group" is a hydrogen atom. Chirality
describes the handedness of a molecule that is observable by the ability of a
molecule to rotate the plane of polarized light either to the right (dextrorotatory) or to the left (levorotatory). All of the amino acids in proteins exhibit
the same absolute steric configuration as L-glyceraldehyde. Therefore, they are all L-a-amino acids. D-amino acids are never found in proteins, although they exist in
nature. D-amino acids are often found in polypetide
antibiotics.
The aromatic R-groups in amino acids absorb ultraviolet light with an
absorbance maximum in the range of 280nm. The ability of proteins to absorb
ultraviolet light is predominantly due to the presence of the tryptophan which
strongly absorbs ultraviolet light.
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The Peptide Bond
Peptide bond formation is a condensation reaction leading to the
polymerization of amino acids into peptides and proteins. Peptides are small
consisting of few amino acids. A number of hormones and neurotransmitters are
peptides. Additionally, several antibiotics and antitumor agents are peptides.
Proteins are polypeptides of greatly divergent length. The simplest peptide, a
dipeptide, contains a single peptide bond formed
by the condensation of the carboxyl group of one amino acid with the amino group
of the second with the concomitant elimination of water. The presence of the
carbonyl group in a peptide bond allows electron resonance stabilization to
occur such that the peptide bond exhibits rigidity not unlike the typical -C=C-
double bond. The peptide bond is, therefore, said to have partial double-bond character.
 |
| Resonance stabilization
forms of the peptide
bond |
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This article has been modified by Dr. M. Javed Abbas.
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20:34 21/12/2002 |