Chemistry of

Amino Acids
By

R. Mautsa
 Objectives

• Describe the basic structure & function

of an amino acid

• Classify amino acids according to the

nature of their side chains
 Objectives

• Discuss the acid-base properties of

amino acids

• Define the isoelectric point of an amino

acid and explain its significance
 Amino Acids

• 20 common amino acids

• Monomeric units of proteins

 Structure of Amino Acids
Each amino acid is made up of:
• amino group
• carboxyl group
• an H atom
• a characteristic side chain called R group
bonded to the alpha C atom, therefore called a-
amino acids
 Characteristics of Amino Acids
• At pH of 7, the amino group is protonated
(NH3+) & carboxyl group is ionized (COO-)
– amino acid is called a zwitterion

• The acidic & basic groups of the aa react

with each other to form a zwitterion

• No net charge
– Electrically neutral
Characteristics of Amino Acids

• a carbon is chiral or asymmetric

• 4 different groups are attached to the

carbon

– exception is glycine
 Characteristics of Amino Acids
• Amino acids exist as stereoisomers
– Same molecular formula, but different
arrangement of groups

– Designated D(right) or L(left)

• Chiral centre allows for stereoisomerism
Characteristics of Amino Acids
• Amino group is present on right-hand side
of a-carbon* in D-amino acids
• NH3+ on right = D

• Amino group is present on left-hand side

of a-carbon* in L-amino acids
• NH3+ on left = L
• All aas found in proteins are in L- form
• D- aas are
– Not not involved in metabolic pathways of
eukaryotes

• But important in structure & metabolism of

bacteria
– e.g., D-alanine and D-glutamic acid found in
bacterial cell walls
 Classification of amino acids

• 20 natural amino acids

• Several methods of classifying them

i. According to their polarity

ii. According to the nature of side chains

iii. On basis of their nutritional importance

 i) Classification according to polarity

• The side chain of the amino acid may be polar

or non-polar
• Accordingly, the amino acid may be polar or
non-polar amino acids
NB
• non-polar amino acids are not absolutely non-polar
• they are less polar and less soluble in polar solvents
than the polar amino acids
Polar and non polar amino acids
Polar amino acids Non-polar amino
acids
• Have ionizable groups • Have no ionizable
in side chains groups in side chains

• Include glycine, serine, • Include alanine, valine,

threonine, cysteine, leucine, isoleucine,
aspartate, glutamate, methionine,
asparagine, glutamine, phenylalanine,
tyrosine, lysine, tryptophan and proline
arginine and histidine
ii) Classification according to nature of
side chain
• The amino acids may be divided into
several groups on this basis
According to chemical nature of side chains, amino
acids can be divided into those having:

• Aliphatic side chains (5)

• Side chains having a hydroxyl group (2)
• Side chains containing sulphur (2)
• Side chains having acidic groups or their
amides (4)
• Side chains having basic groups (3)
• Side chains containing aromatic rings (3)
• Imino group (1)
i)
ii)
iii)
iv)
v)
vi)
vii)
 iii) Classification according to nutritional
importance

According to nutritional importance,

amino acids may be divided into:

Semi-
Essential Non-essential
essential
amino acids amino acids
amino acids
 pK1
pK2 pK R
Amino Acid Symbol Structure* (COOH
(NH2) 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

 Essential Aas
• Essential aas - required in nutrition of most
animals
– Cannot be synthesized by body
– If not provided in diet, protein synthesis will be impaired
– 8 aas essential to human nutrition
– Animal proteins generally contain all the essential aas
– valine., leucine, isoleucine, threonine, methionine,
lysine, phenylalanine and tryptophan
 Semi essential amino acids
• Synthesis of semi-essential aas is below
their requirement in childhood
• Therefore must be provided in the diet of
children
• Arginine and histidine
 Non-essential aas
• Non-essential aas - can be biosynthesized
– All tissues have some capability for synthesis
of non-essential aas
– Glycine, alanine, serine, cysteine, aspartate,
glutamate, asparagine, glutamine, tyrosine,
and proline are
 Acid-Base Properties of Aas

• Aas have both acidic & basic properties

due to presence of functional groups,
NH2 & COOH

• Will form salts when treated with acids

or alkalis
 Acid Dissociation Constants for
Weak Acids

• Weak acids partially dissociate in water

HA(aq) ↔ H+(aq) + A-(aq)

• Dissociation constant is:

Ka = [H+(aq)] [A-(aq)] mol dm-3
[HA]
 Acid Dissociation Constants for
Weak Acids

• The weaker the acid, the smaller the Ka

• pKa = -log10 Ka

• Ka = antilog (-pKa)

pKa is a number that describes the acidity of a particular

molecule. The lower the value of pKa, the stronger the acid
 Acid Dissociation Constants for
Weak Acids
Ka = [H+] [A-]
[HA]

log Ka = log [H+] [A-]

[HA]

log Ka = log [H+] + log [A-]

[HA]
 Acid Dissociation Constants for
Weak Acids
-log[H+] = -log Ka + log [A-]
[HA]

• Henderson-Hasselbach equation

• If [A-] = [HA], then

• pH = pKa + log 1
• pH = pKa
 Acid Dissociation Constants for
Weak Acids

• If [A-] > [HA], pH of solution > pKa of acid

• If [A-] < [HA], pH of solution < pKa of acid

 Acid-Base Properties of Aas
• Aas have at least two ionizing groups, the
carboxyl & amino groups

• Of 20 aas 13 have 2 ionizable groups

• 7 have 3 ionizable groups since the R-group

can be ionized
 Acid-Base Properties of Aas
• Both amine & carboxyl groups are in ionized
form in aqueous soln & biological pH values
– Eg. At neutral pH glycine occurs a zwitterion

• pKa for amino group is 8.7-10.7

• pKa for carboxylic acid group is 1.8-2.5

• pKa of ionizable grp is pH at which
there are equal amounts of protonated
& unprotonated species
• Eg For glycine, pKa = 2.34
– At pH 2.34,
– [H3N+--CH2--COOH] = [H3N+--CH2--COO-]
• If pH< pKa, a group is mainly
protonated (NH3+ or COOH)

• If pH > pKa, a group is mainly

unprotonated or anion form (NH2 or
COO-)

• If pH = pKa, then [conjugate base]

=[weak acid].
• pH of environment & pKa of
ionizable groups will determine
charge associated with aa
 The Isoelectric Point
• At any given pH, aas have different net
charges
• The pH at which a given aa has a net
charge of zero is the isoelectric point,
pI
• For most aas, pI is midway between
their 2 pKa values
 The Isoelectric Point

• For aas with ionizable side chains, pI is

at:
– Higher pH for basic side chains
– Lower pH for acidic side chains
 Titration Curves
• Can use titration curves for aas to show
ionizable groups
• If pH > pI, aa is -vely charged

• If pH < pI, aa is +vely charged

• If pH = pI, aa has no charge

Titration curve for Alanine
Calculation of pI from given pKa values

• Isoelectric point of an amino acid is the pH at which

the molecule carries no net charge.

• It can be calculated by the average of the relevant

pKa.

• How does one choose the relevant pKa

values?
• For this we, should refer to the titration curve of the
amino acid
 For a neutral amino acid

From the curve, we can infer that the pI is simply the average of the two pKa values of the
carboxylic acid and the amino group.
 For a basic amino acid

From the curve we can infer that the pI is simply the average of the two
pKa values of the two amino groups.
The pKa of the carboxylic acid group is not relevant
 For an acidic amino acid

From the curve, we can infer that the pI is simply the average of
the two pKa values of the two carboxylic acid groups.
The pKa of the amino group is not relevant.
Here are examples for all three cases:
 Electrophoresis
• Aas can be separated based on their
charge in solution at a given pH
• Eg at pH 7
– Alanine is approximately neutral
– Arginine is mainly +ve
– Glutamic acid is mainly –ve
• Depending on their charge, the molecules
migrate towards either a +ve or a –ve
electrode
 Peptide bond
• The bond by which aas are linked with each
other in peptides and proteins

• Formed by a condensation reaction in

which a molecule of water is removed,
broken by hydrolysis

• Formed between a carboxyl group of one

aa and amino group of another amino acid
 Peptide bond

Rxn is complex: occurs in stages and requires the presence of enzymes, coenzymes, and other
factors
 Peptides
• Naming goes from N-terminus to C-
terminus

• -ine ending of aa is replaced by –yl

except for last one
– Eg threonylvaline is a dipeptide different
from valylthreonine
 Proteins
• Large molecules made up of chains of
amino acids
• Are found in every cell in the body
• Are involved in most of the body’s
functions and life processes
• The sequence of amino acids is
determined by DNA
 Structure of proteins
• Made up of chains of amino acids; classified by
number of amino acids in a chain
– Peptides: fewer than 50 amino acids
• Dipeptides: 2 amino acids
• Tripeptides: 3 amino acids
• Polypeptides: more than 10 amino acids
– Proteins: more than 50 amino acids
• Typically, 100 to 10,000 amino acids linked together
• Chains are synthesizes based on specific bodily
DNA
 Four levels of structure

– Primary structure
– Secondary structure
– Tertiary structure
– Quaternary structure
 Protein Structure
• primary (1°) structure: the amino acid sequence
• secondary (2°): frequently occurring
substructures or folds
• tertiary (3°): three-dimensional arrangement of
all atoms in a
• single polypeptide chain
• quaternary (4°): overall organization of non-
covalently linked
• subunits of a functional protein.