AMINO ACIDS

Amino acids are the organic compounds having

one or more carboxyl group (organic acid) and
one or more amino group (organic base) in the
same molecule.
Amino acids have primary amino group and a
carboxylic acid bonded to same carbon.

Amino acids share a general structure

• An amino group (-NH2) which is basic
• A carboxyl group (-COOH) which is
acidic
• An alpha carbon attached to a
hydrogen
• An R group consisting of a variable
side chain
• Protonation state at phyological pH 7
Proteins are polypeptides consisting of one or more polypeptide chains. Simply,
they are polymers of amino acids
Hydrolysis of proteins yields a mixture of 20 common amino acids.

Hydrolysis

An -amino acid

• Proteins are polyamides, and their monomeric units are

comprised of about 20 different α-amino acids because
they have a primary amino group and a carboxylic acid
substituent group on the same carbon atom with the
exception proline, has a seconadry amino group.
Proline
• Cells use α-amino acids to synthesize proteins. (Imino acid)
 Nomenclature of amino acids

Each amino acid can be represented

by a single letter code or a three-
letter abbreviation

The three letters abbreviations

are, in most cases, taken from the
first three letters of the
corresponding amino acid.

The one letter symbols are usually

the fist letter of the amino acid
residue’s name. However, for those
set of residues that have the same
first letter, this is only true of the
most abundant residue of the set.
 Classification of Amino acids

Depending upon the variable side chains (R group), amino acids are classified

Aliphatic amino acids Aromatic amino acids Sulfur containing amino acids

Depending upon the acidity and basicity of amino acids, they are classified

Neutral Acidic Basic

Depending upon the polarity of side chains (R group), amino acids are classified

Non polar Polar uncharged Polar charged

Depending upon the in-vivo synthesis, amino acids are classified

Essential Non-essential
 Aliphatic (alkane) Amino Acids

Alanine Valine Leucine Isoleucine

Aromatic Amino Acids Sulfur Containing Amino Acids

Phenylalanine Tyrosine Tryptophan Methionine Cysteine

Neutral Amino Acids: These amino
acids contain one amino group and one
carboxyl group
• Zwitterion at physiological pH Glycine Alanine

Acidic Amino Acids: Amino acids have side

chain that carboxyl group that is these amino
acids contain one amino and two carboxyl
groups.
• Negatively charged at physiological pH
• Carboxyl groups function as nucleophiles in Aspartic acid Glutamic acid
some enzymatic reactions

Basic Amino Acids: Amino acids

containing side chains with amino
groups that is they contain two amino
and one carboxyl group
• Hydrophillic nitrogenous bases
• Positively charged at physiological pH

Lysine Arginine Histidine

 Nonpolar (hydrophobic) amino acids

•Aliphatic hydrocarbons • Aromatic hydrocarbon

Glycine (R group = -H) Phenylalanine and tryptophan
Alanine (R group = -CH3) • Sulfur-containing amino acids
Valine, Leucine, Isoleucine Methionine
(R= Extended aliphatic chains) • Imino acid - Proline

Polar (hydrophilic), uncharged amino acids

Serine Threonine
Tyrosine

Polarity contributed by hydroxyl group (-OH) of Serine, Threonine and Tyrosine

 Asparagine Glutamine Cysteine
• Asparagine and Glutamine have amide side chains that contributes in polarity
• Cysteine contains a sulfhydryl side chain (Thiol group) that contributes in polarity
Polar (hydrophilic), charged amino acids
Basic Amino acids – Histidine, Lysine and
Arginine
Acidic Amino acids – Glutamic acid and
aspartic acid

Lysine Arginine Histidine

Aspartic acid Glutamic acid
 Essential and non-essential amino acids

Amino acids can be synthesized by all living

organisms, plants and animals. Many higher
animals, however, are deficient in their ability
to synthesize all of the amino acids they need
for their proteins. Thus, these higher animals
require certain amino acids as a part of their
diet.

Where do organisms obtain their amino

acids?
Bacteria, yeast and plants make all of their own
Animals make the “nonessential” but not the
“essential” amino acids
• Some amino acids are made by multi-step
biosynthetic pathways
• Some are made from metabolic intermediates
of other amino acids
– Tyrosine is made from phenylalanine
– Alanine from pyruvate
 Essential amino acid
• An essential amino acid or indispensable amino acid is an amino acid that cannot be
synthesized internally by the human body, and therefore must be supplied in the diet.
• Ten amino acids are generally regarded as essential for humans. They are: arginine,
isoleucine, leucine, lysine, threonine, tryptophan, methionine, histidine, valine and
phenylalanine.
• Arginine is required for the juvenile but not for adults
• A mnemonic used to remember these acids runs: I Like Light That Tries Making Home
Very Pretty.
• In addition, the amino acids arginine, cysteine, glycine, glutamine and tyrosine are
considered conditionally essential, meaning they are not normally required in the diet,
but must be supplied exogenously to specific populations that do not synthesize it in
adequate amounts.
• An example would be with the disease Phenylketonuria (PKU). Individuals living with
PKU must keep their intake of phenylalanine extremely low to prevent mental retardation
and other metabolic complications. However, phenylalanine is the precursor for tyrosine
synthesis. Without phenylalanine, tyrosine cannot be madeand so tyrosine becomes
essential in the diet of PKU patients.
• Which amino acids are essential varies from species to species, as different metabolisms
are able to synthesize different substances.
 Phenylketonuria
• Phenylketonuria is a disease that is occurred due to inborn errors of metabolism of
phenylalanine caused by inherited mutations leads to a defect in an enzyme required
for a metabolic pathway of phenylalanine to tyrosine.
• Phenylalanine is metabolized to tyrosine by phenylalanine hydroxylase. Individuals
with phenylketonuria (PKU) lack the enzyme
• Instead of being hydroxylated to tyrosine, phenylalanine is transaminated to
produce phenylpyruvate and other metabolites
• Accumulation of these metabolites can lead to mental retardation
• Individuals with PKU must restrict their dietary intake of peptides containing the
amino acid, phenylalanine.
NH2

HO CH2 C COOH
H
Phenylalanine
NH2 hydroxylase Tyrosine
O
CH2 C COOH
H PKU
CH2 C COOH
Phenylalanine
Phenylpyruvic acid
 Stereochemistry of amino acids
Optical Activity: The organic compounds, when their solution is placed in the path
of plane polarized light, the compounds have the property to rotate the plane of light
through a certain degree which may be either to the right (dextrorotatory /clockwise)
or to the left (levorotatory/anticlockwise). This property of a substance of rotating
the plane of polarized light is called optical activity and substance is said to be
optically active.

• Optically active compounds have asymmetic centers/chiral centers that is they

contain tetrahedral carbon atoms that have four different substituents.
• Optically active molecules have an asymmetry such that they are not
superimposable on their mirror images.
• Dextrorotatory molecules are designated by the prefix (+) and their levorotatory
enantiomers by the prefix (-). In addition, the lower case letters d (dextro) and
l (levo) are used.

Why the -amino acids are optically active?

All -amino acids with the exception glycine have the ability to rotate plane of
polarized light and are referred as optically active because
• The alpha carbon of all the amino acids (except glycine) are chiral/ asymmetric
• Their mirror images are not superimposable
 Mirror
Asymmetric plane
center

Alanine

Why is the exception in glycine?

H
Glycine is not optically active because
• It does not have asymmetric center, the H2N C COOH
alpha carbon contain two hydrogen atoms
• Mirror images are superimposable H

In nature, amino acids never exist as recemic mixture i.e. they are always
present in optically active form
 D and L system for amino acids
The optical isomers of amino acids do not provide any interpretable indication of
the absolute configuration (spatial arrangement) of the chemical groups about a
chiral center.
D-L system has been used to specify the relative configuration at the asymmetric
carbon. In this system, the configuration of the groups about the asymmetric center
is related to that of glyceraldehyde, a molecule with one asymmetric center.
According to Fischer convention, the dexoroatory (+) and the levorotatory (-)
stereoisomers of glyceraldehydes are designated as D-glyceraldehyde and
L-glyceraldehyde, respectively.

D-glyceraldehyde L-glyceraldehyde
The configuration of groups about a chiral center can be related to that of the
gyceraldehyde by chemically converting these groups to those of glyceraldehyde
using reaction of known stereochemistry.
For -amino acids, the arrangement of the amino, carboxyl, R and H groups about the
alpha carbon atom is related to that of the hydroxyl, aldehyde, CH 2OH and H groups,
respectively. Generally, in the L form of glyceraldehyde the hydroxyl group is on the left
side of the molecule, and in the D form it is on the right side so that in an amino acid, the
position of the amino group on the left or right side of the alpha carbon determines the L
or D designation.
If the configuration at the asymmetric carbon atom of an amino acid can be related to
D-configuration of glyceraldehyde, belongs to D-series and if it can to L-configuration
of glyceraldehyde belongs to L- series

D-glyceraldehyde L-glyceraldehyde

D-alaline L-alaline

D-phenylalanine L-phenylalanine
All the amino acids obtained from proteins have the L-stereochemical configuration
indicating that only the L- isomers are inserted into proteins using the normal protein
synthesis machinery.
Moreover, in synthetic amino acids, only belonging to L-series are biologically active.
D-amino acids occur rarely
• Some peptide antibiotics- D-phenylalaline occurs in the polypeptide antibiotic.
Example: Germicidin-S
• Bacterial cell walls

Amino acids with two chiral centers were named by allotting a name to the first
diastereoisomer then assigned the same name but with the prefix allo-.

D-isoleucine L-isoleucine D-alloisoleucine L-alloisoleucine

 Acid-Base Properties of Amino Acids
An amino acid has both a basic amine group and an acidic carboxylic acid group
so that there is an internal transfer of a hydrogen ion from the -COOH group to
the -NH2 group to leave an ion with both a negative charge and a positive charge.
Therefore, amino acids exist as dipolar ions, a form in which the carboxyl group
is present as a carboxylate ion, —CO2-, and the amino group is present as an
aminium ion, —NH3+. Dipolar ions are also called zwitterions.
This is the form that amino acids exist in even in the solid state. If you dissolve
the amino acid in water, a simple solution also contains this ion.

O O

H H
R C C O H R C C O

NH2 NH3
Adding an acid to an amino acid solution: Adding an alkali to an amino acid solution:
The pH by is decreased by adding an acid to a The pH of a solution of an amino acid is increased
solution of an amino acid, the –COO- part of the by adding hydroxide ions, the hydrogen ion is
zwitterion picks up a hydrogen ion. removed from the -NH3+ group.

O O O
H H OH H
H
R C C OH R C C O R C C O

NH3 NH3 NH2

In aqueous solution, an equilibrium exists between the dipolar ion and the anionic and
cationic forms of an amino acid.
 Isoelectronic point, pI
The isoelectronic point is the pH at which the amino acid does not migrate in an electric
field. This means it is the pH at which the amino acid is neutral, i.e. the zwitterion form is
dominant. The pI is given by the average of the pKas that are involved for the formation of
the zwitterion
• The side chain "R" should be considered for the calculation of the isoelectronic point
• Neutral side chains
• These amino acids are characterised by two pKas : pKa1 and pKa2 for the carboxylic acid
and the amine respectively. The isoelectronic point will be halfway between, or the average
of these two pKas, i.e.   pI = 1/2 (pKa1 + pKa2).
• At very acidic pH (below pKa1) the amino acid will have an overall +vecharge
• At very basic pH (above pKa2 ) the amino acid will have an overall -ve charge. 

2.34 9.6

Glycine, pKa1= 2.34 and pKa2 = 9.6, pI = 5.97.

 Acid-base titration of a neutral amino acid

If alanine is dissolved in a strongly acidic solution (e.g., pH 0), it is present in

mainly a net cationic form. In this state the amine group is protonated (+charge)
and the carboxylic acid group is neutral (has no charge). As is typical of α -amino
acids, the pKa for the carboxylic acid hydrogen of alanine is considerably lower
(2.3). The protonated amine group of an α -amino acid is also acidic, but less so
than the carboxylic acid group. The pKa of the aminium group in alanine is 9.7.
The carboxylic acid proton is always lost before a proton from the aminium group
in an α-amino acid. The isoelectric point (pI) of an amino acid such as alanine is
the average of pKa1 and pKa2
 • Acidic side chains
The pI will be at a lower pH because the acidic side chain introduces an "extra"
negative charge. So the neutral form exists under more acidic conditions when
the extra -ve has been neutralised. 

pKa1 1.88
pKa2 9.68
pKa3 3.65
Aspartic acid
• Aspartic acid shows, the neutral form is dominant between pH 1.88 and 3.65,
• pI is halfway between these two values, i.e.   pI = 1/2 (pKa1 + pKa3),  so pI = 2.77.
Basic side chains
The pI will be at a higher pH because the basic side chain introduces an "extra" positive
charge. So the neutral form exists under more basic conditions when the extra +ve has
been neutralised. • Starting from the top, as we add base, the most acidic
proton is removed first (COOH), then the pyrrole NH
then finally the amino NH. These takes us through each
of the forms in turn.
• At pH < 1.82, A is the
dominant form.In the range
pKa1 1.82

• In the range 1.82 < pH < 6.02

B is the dominant form.
pKa3 6.02
• In the range 6.02 < pH < 9.17
C is the dominant form, zwiterion ion
pI = 1/2 (pKa2 + pKa3),  so pI = 7.6

pKa2 9.17

• At pH > 9.17, D is
the major form in solution.
 Methods of Preparation of Amino Acids

Amination of α-halo acids: Amino acids can be prepared by the amination of α-halo
acids with excess of ammonia.

Acids are converted to α-halo acids by the Hell-Volhard- Zelinsky reaction and α-halo
acids are treated with excess ammonia to produce the amino acids

X2, P NH3
R-CH2-COOH R-CH-COOH R-CH-COOH
Excess

X NH2
Amino acid

X2, P NH3
CH3-CH2-COOH CH3-CH-COOH CH3-CH-COOH
Excess
Propionic acid Alaline
X NH2
 Malonic ester synthesis

COOC2H5 COOC2H5
C6H5CH2Cl KOH
Na CH HC CH2C6H5
Heat
COOC2H5 COOC2H5
Sodiomalonic ester

COOH COOH
Br2
HC C
Heat
CH2C6H5 Br CH2C6H5
Ether

COOH COOH
Benzylmalonic acid Bromobenzylmalonic acid

C6H5CH2CH-COOH NH3 C6H5CH2CH-COOH

Excess
Br NH2
Phenyl alanine
Gabriel phthalimide synthesis: An ester of α-halo acid is treated with potassium
phthalimide to form the corresponding substituted which on hydrolysis gives
phthalic acid and amino acid

O O

C C
ClCH2COOC2H5
N K N-CH2COOC2H5

C C

O O
Potassiumphthalimide
COOH
H2O
NH2-CH2-COOH C2H5OH
HCl
Glycine COOH

Phthalic acid
 Phthalimidomalonic ester synthesis

This method is a modification of Gabriel phthalimide synthesis and is a

combination of malonic ester and Gabriel phthalimide synthesis. It involves
the following steps:

• Treatment of potassium phthalimide with diethylbromomalonate

(ethylbromomalonate)

• Treatment of the imidomalonate with base to remove the α-hydrogen

• Treatment with RX, which gives a typical malonic ester alkylation reaction

• Acid hydrolysis will produce the amino acid

 O O

C COOC2H5 C COOC2H5

N K Br CH N CH

C COOC2H5 C
COOC2H5
O Ethylbromomalonate O
Potassiumphthalimide Phthalimidomalonic ester

NaOC2H5 Base

O O

C COOC2H5 C COOC2H5

N C CH2C6H5 ClCH2C6H5 N C Na

C COOC2H5 C COOC2H5
O O
H2O
Heat
H / OH
COOH
C6H5CH2CH-COOH
C2H5OH CO2
NH2
Phenyl alanine COOH

Phthalic acid
 Preparation of Metheonine

O O

C COOC2H5 C COOC2H5
ClCH2CH2SCH3
N C Na N C CH2CH2SCH3

C C
COOC2H5 COOC2H5
H2O
O Heat O
H

COOH

HOOC-CHCH2CH2SCH3
C2H5OH CO2
NH2 COOH

Metheonine Phthalic acid

 Preparation of Aspartic acid

O O

C COOC2H5 C COOC2H5
ClCH2COOC2H5
N C Na N C CH2COOC2H5

C C
COOC2H5 COOC2H5
H2O
O Heat O
H

COOH

HOOC-CHCH2COOH
C2H5OH CO2
NH2 COOH

Aspartic acid Phthalic acid

 Reactions of Amino Acids
Amino acids contain two functional groups : amines and carboxylic acids. So amino acids
undergo the reactions characteristic of those functional groups.
Carboxylic Acid Esterification: Esterification of the carboxylic acid is usually conducted
under acidic conditions. Under such conditions, amine functions are converted to their
ammonium salts and carboxyic acids are not dissociated. The initial product is a stable
ammonium salt. The amino ester formed by neutralization of this salt is unstable, due to
acylation of the amine by the ester function.
(1) Typical Fischer esterification involving methanol.
(2) Benzylation of the two carboxylic acid functions of aspartic acid, using
p-toluenesulfonic acid as an acid catalyst.

(1)

(2)
Amine Acylation: In order to convert the amine function of an amino acid into an
amide, the pH of the solution must be raised to 10 or higher so that free amine
nucleophiles are present in the reaction system. Carboxylic acids are all converted to
carboxylate anions at such a high pH, and do not interfere with amine acylation
reactions.
(1) An acid chloride serves as the acylating reagent. This is a good example of the
superior nucleophilicity of nitrogen in acylation reactions, since water and hydroxide
anion are also present as competing nucleophiles.
(2) This reaction employs an anhydride-like reagent for the acylation

(1)

(2)
Ninhydrin Reaction: In addition to these common reactions of amines and carboxylic
acids, common alpha-amino acids, except proline, undergo a unique reaction with the
triketohydrindene hydrate known as ninhydrin. Among the products of this unusual
reaction is a purple colored imino derivative, which provides as a useful color test for
these amino acids, most of which are colorless.
• A common application of the ninhydrin test is the visualization of amino acids in
paper chromatography.

 
    
                                                                                                                                    
Specific Oxidation: The mild oxidant iodine reacts selectively with certain
amino acid side groups. These include the phenolic ring in tyrosine, and
the heterocyclic rings in tryptophan and histidine, which all yield products
of electrophilic iodination.

In addition, the sulfur groups in cysteine and methionine are also oxidized
by iodine. Quantitative measurent of iodine consumption has been used to
determine the number of such residues in peptides.

Cysteine-Cystine Interconversion
Metabolism of amino acids

Metabolism of amino acids consists of three stages:

• Deamination, the removal of amino group, whereby amino groups are converted either
to ammonia or to the amino group of asparate. Both of these substances are derived from
substrate, a product of most deamination reactions
• Incorporation of ammonia and asparate nitrogen to produce urea for excretion
• Conversion of amino acid carbon skeleton ( a-keto acids produced by deamination) to
common metabolic intermediates.

-Amino acids -Keto acids

Transamination
-Ketoglutarate L- Glutamate

Oxidative
deamination

NH3 CO2
Urea cycle Urea
Transamination
Transamination (or aminotransfer) is the reaction between an amino acid and an alpha-keto
acid. The amino group is transferred from the former to the latter; this results in the amino
acid being converted to the corresponding α-keto acid, while the reactant α-keto acid is
converted to the corresponding amino acid (if the amino group is removed from an amino
acid, an α-keto acid is left behind).
• Transamination is accomplished by enzymes called transaminases or aminotransferases.
• Pyridoxal phosphate (coenzyme) acts as carriers for amino group
 Transamination reactions occurs in two stages:
The amino group of an amino acid is transported to the enzyme, producing corresponding
keto acids and the aminated enzyme

Amino acid + Enzyme A-keto acid + Enzyme-NH2

The an amino acid is transported to keto acids acceptor (a-ketoglutarate), forming the
amino acid product (glutamate) and regerating enzyme.

A-Ketoglutarate + Enzyme-NH2 Glutamate + Enzyme

To carry the amino group, amino tranferase require participation of an aldehyde

containing co-enzyme, Pyridoxal -5-phosphate, a derivative of pyridoxine. The
amino group ccommodated by conversion of this co-enzyme to pyridoxamine-5-phosphate
Oxidative deamination, an amino acid is converted into the corresponding keto acid by
the removal of the amine functional group as ammonia and the amine functional group is
replaced by the ketone group. The ammonia eventually goes into the urea cycle.
• Oxidative deamination is accomplished by enzymes called Glutamate dehydrogenase,
• In contrast to the transamination reactions which merely swop amino groups from one
compound to another, Glutamate dehydrogenase catalyses a net loss of nitrogen from the
amino acid pool, therefore the process is therefore termed "oxidative deamination".

-Ketoglutarate

Oxidative deamination occurs primarily on glutamic acid because glutamic acid

was the end product of many transamination reactions
Strecker synthesis: The strecker synthesis of amino acid involves two steps:
Reaction