Amino Acids
- A basic amino group (-NH2)
- An acidic carboxyl group ( -COOH)
- A hydrogen atom (-H)
- A distinctive side chain (-R)
In neutral solution (PH = 7), both the α- amino and α carboxyl group are ionized resulting the
charged form of an amino acids called zwitterion (dipolar) as shown in the figure below.
In dipolar (zwitterion) form the amino group is protonated (-NH3
+
) and the carboxyl group is
dissociated (deprotonated) (-COO-
) leading to a net charge zero.
Stereochemistry (Optical activity)
Stereochemistry mainly emphasizes the configuration of amino acids at the α carbon atom,
having either D or L- isomers.
Out of the 20 amino acids, proline is not an α amino acid rather an α - imino acid. Except for
glycine, all amino acids contain at least one asymmetric carbon atom (the α - carbon atom).
Classification of Amino Acids
L-Amino acids are the building blocks of proteins. They are frequently grouped according to
the chemical nature of their side chains. Common groupings of amino acids are aliphatic,
hydroxyl/sulfur, cyclic, aromatic, basic, acidic and acid amides. Links to individual amino
acids are given below:
I. Structural Classification
This classification is based on the side chain radicals (R-groups) as shown in the table 5.1.Each
amino acid is designated by three letter abbreviation eg. Aspartate as Asp and by one letter
symbol D.
II. Electrochemical classification
Amino acids could also be classified based on their acid – base properties
Acid amino acids (Negatively charged at pH = 6.0)
Example:
- aspartic acid - CH2 – COO-
- glutamic acid - CH2 – CH2 – COO
E. III. Biological or Physiological Classification
This classification is based on the functional property of amino acids for the organism.
1. Essential Amino Acids
Amino acids which are not synthesized in the body and must be provided in the diet to meet an
animal’s metabolic needs are called essential amino acids. About ten of the amino acids are
grouped under this category indicating that mammals require about half of the amino acids in
their diet for growth and maintenance of normal nitrogen balance.
2. Non- Essential Amino Acids
These amino acids are need not be provided through diet, because they can be biosynthesized
in adequate amounts within the organism.
Essential and Non essential amino acids are as shown in the Table 5.2:
Table 5.2: Essential and Non-Essential Amino Acids
3. Semi-essential amino acids
Two amino acids are grouped under semi-essential amino acids since they can be synthesized
within the organism but their synthesis is not in sufficient amounts. In that they should also be
provided in the diet.
The set of essential amino acids required for each species of an organism can be an indicative
of the organism propensity to minimal energetic losses on the synthesis of amino acids. Semi
essential amino acids include Arginine and Histidine.
IV. Classification Based on the Fate of Each Amino acid in Mammals.
Amino acids can be classified here as Glucogenic (potentially be converted to glucose),
ketogenic (potentially be converted to ketone bodies) and both glucogenic and ketogenic.
I. Glucogenic Amino Acids
Those amino acids in which their carbon skeleton gets degraded to pyrurate, α ketoglutarate,
succinyl CoA, fumrate and oxaloacetate and then converted to Glucose and Glycogen, are
called as Glucogenic amino acids.
These include:-
Alanine, cysteine, glycine, Arginine, glutamine, Isoleucine, tyrosine.
II. Ketogenic Amino Acids
Those amino acids in which their carbon skeleton is degraded to Acetoacetyl CoA, or acetyl
CoA. then converted to acetone and β-hydroxy butyrate which are the main ketone bodies are
called ketogenic amino acids.
These includes:-
Phenylalanine, tyrosine, tryptophan, isoleucine, leucine, and lysine.
These amino acids have ability to form ketone bodies which is particularly evident in untreated
diabetes mellitus in which large amounts of ketone bodies are produced by the liver (i.e. not
only from fatty acids but also from ketogenic amino acids)
Degradation of Leucine which is an exclusively ketogenic amino acid makes a substantial
contribution to ketone bodies during starvation.
III. Ketogenic and glucogenic Amino Acids
The division between ketogenic and glucogenic amino acids is not sharp for amino acids
(Tryptophan, phenylalanine, tyrosine and Isoleucine are both ketogenic and glucogenic).
Some of the amino acids that can be converted in to pyruvate, particularly (Alanine, Cysteine
and serine, can also potentially form acetoacetate via acetyl CoA especially in severe starvation
and untreated diabetes mellitus.
Fig 5.3. Ketogenic, Glucogenic and Glucogenic-Ketogenic amino acids
Ketogenic and Glucogenic amino acids are as indicated in the chart except Leucine and
Lysine which are exclusively ketogenic
V. Classification Based on Participation in Protein Synthesis.
I. Non-Standard Amino Acids
In addition to the 20 standard amino acids, proteins may contain non- standard (proteogenic)
amino acids, which are normally components of proteins but created by modification of the
standard amino acids.
Among the non – standard amino acids 4 – hydroxyproline a derivative of proline, 5-
hydroxylysine derivative of lysine where both are found in collagen, a fibrous protein of
connective tissues. 6 N – methyllysine a constituent of myosin, a contractile protein of
muscle and γ-carboxy glutamate a derivative of glutamate, which is found in the blood
clotting protein prothrombin
Fig:5. 4 Non standard amino acids
II. Non – Proteogenic Amino Acids
These amino acids occur in free or combined state, unlike in proteins,and play important roles in
metabolism in plasma, free amino acids are usually found in the order of 10 to 100 μ mol/L,
including many that are not found in proteins.
Citrulline ,for example, is an important metabolite of L. arginine and a product of Nitric - Oxide
synthase, an enzyme that produces nitric oxide an important signaling molecule.
Antibiotics - gramicidin and antimycin D
γ-aminobutryric acid - which acts as an inhibitory neurotransmitter
D - Alanine - a component of vitamin, panthothenic acid, are some of the nonproteogenic amino acids.
Fig 5.5: Non-Proteogenic Amino acids
Ionization States of Amino Acids
Amino acids are amphoteric molecules, that is, they have both basic and acidic groups.
Monoamine and monocarboxylic acids are ionized in different ways in solution, depending on
the pH of solution.
At pH 7, the “zwitterions” H+
3N – CH2 – COO-
is the predominant species of Glycine in solution
and the overall molecule is electrically neutral. At acidic pH the α amino group (α -NH2 ) group
is fully protonated and positively charged, yielding H+
3N – CH2 – COOH, while at alkaline pH
glycine exists primarily as the anionic H2N – CH2 – COO- species, (Negatively charged
species).
At the pH intermediate between pka (a measure of the tendency of group to give up a proton,
with that tendency, decreasing 10 fold as the pka increase by one unit) of the amino and
carboxyl groups, known as isolectric point (PI), the zwitter ionic form of the amino acid has no
net charge.
PI can be calculated for each amino acid with mono amine and mono basic groups as follows:
Acid Base Properties of Amino Acids
When a crystalline amino acid, such as Alanine is dissolved in water, it can act as either an acid
(proton donor) or a base (proton acceptor)
According to Laury and Bronsted theory of acid and bases, and acid is a proton donor and a
base is a proton acceptor.
Example : Alanine acting as proton donor (Acid)
Substances having such dual nature are said to be Amphoteric and are often called
Ampholytes
Titration Curves of Amino Acids
Titration involves the gradual addition or removal of protons.
E.g. Glycine
Each molecule of added base (NaOH) to glycine results in the net removal of one proton. The
titration curve plot has two distinctive stages each corresponding to the removal of one proton
from glycine. Each of the two stages resembles in shape the titration curve of monoprotic acid
(such as acetic acid).
At very low pH the predominant ionic species of glycine is
At the mid point in the first stages of titration in which the COOH group of glycine loses its
proton where equimolar concentrations of proton donor
(H3N+
– CH2 – COOH) and proton acceptor (H3N+
– CH2 – COO-
) species are present. At this
point pH = pka of the protonated group being titrated for Glycine. The pH at the midpoint is 2.34.
Thus its COOH group has a PK
a of 2.34.
As the titration proceeds another important point is reached at pH = 5.97 Here, there exists a
point of inflection at which removal of the first proton it essentially complete and the removal of
the second proton has just begun. At this point glycine exists largely as dipolar ion H3N+
– CH2 –
COO-
(fully ionized) but with no electric charge. This characteristic pH is called as isoelcetric pH
designated as PI or pHI.
So, for glycine, which has no ionizable group as a side chain, the isoelectric point is the
Arithmetic mean of the two PKa Values:
PI = ½ (PK1 + pK2)
= ½ (2.34 + 9.60) = 5.97
Glycine will have a net (-negative) charge above its PI and thus moves toward positive electrode
(anode) when placed in an electric field.
At any pH below its PI, glycine has a net positive charge and moves toward negative electrode
(cathode, when placed in an electric field.)
So, all amino acids with a single α - amino group and a single α - carboxyl group and an
R - group that does not ionize, have titration curves resembling that of glycine.
i.e. PK1 = (the PK of COOH group)
Usually in the range of 1.8 – 2.4
PK2 (of the PK of –NH3 group)
Usually in the range of 8.8 – 11.0
The second stage of the titration curve corresponds to the removal of a proton from the - NH3
group of glycine
The pH at the midpoint of this stage is 9.60 equal to the Pka of – NH+
3 group
The titration to the pH of about 12 in which the predominant form of glycine is H2N – CH2 –
COO-
(negatively charged).
