Amino acids

Associate professor Ljiljana Andrijević

Department of Biochemistry
 Amino acids

• Twenty percent of the human body is made up of protein.

Protein plays a crucial role in almost all biological processes
and amino acids are the building blocks of it.
• A large proportion of our cells, muscles and tissue is made up
of amino acids, meaning they carry out many important
bodily functions, such as giving cells their structure. They also
play a key role in the transport and the storage of nutrients.
Amino acids have an influence on the function of organs,
glands, tendons and arteries. They are furthermore essential
for healing wounds and repairing tissue, especially in the
muscles, bones, skin and hair as well as for the removal of all
kinds of waste deposits produced in connection with the
metabolism.
• Amino acids are building blocks of all proteins, and are linked in series by
peptide bond (-CONH-) to form the primary structure of a protein. Amino
acids possess an amino group, a carboxylic acid group and a varying side
chain that differs between different amino acids.

• There are 20 naturally occurring amino acids, which vary from one
another with respect to their side chains. Their melting points are
extremely high (usually exceeding 200°C), and at their pI, they exist as
zwitterions, rather than as unionized molecules

• Amino acids respond to all typical chemical reactions associated with

compounds that contain carboxylic acid and amino groups, usually under
conditions where the zwitter ions form is present in only small quantities.
All amino acids (except glycine) exhibit optical activity due to the presence
of an asymmetric α – Carbon atom. Amino acids with an L – configuration
are present in all naturally occurring proteins, whereas those with D –
forms are found in antibiotics and in bacterial cell walls.
 Common to all α-amino acids

The structure of an alpha amino acid in its un-ionized form (1) and in • Each amino acid has a carboxyl
ionized form (2)
R – side chains determine properties of proteins group (-COOH), an amino group (-NH2)
and distinctive side chain (R group)
bonded to the α carbon atom
• At physiologic pH ( 7.4), the carboxyl
group is dissociated, forming the
negativly charged carboxylate ion
(−COO− ) and the amino group is
protonated (-NH3+)
• In proteins, almost all of these carboxyl
and amino groups are combined in
peptide
Classification of Amino Acids
Amino acids are generally divided into groups on the basis of their side chains (R
groups).
Amino acids are separated into:
 Nonpolar amino acids

Only carbon and hydrogen in their side chains.

Generally unreactive but hydrophobic.

Determining the 3-D structure of proteins, so they tend

to cluster on the inside of the molecule.
 Nonpolar (Hydrophobic) R Groups
Glycine (Gly) Methionine (Met)

Alanine (Ala)

Phenylalanine (Phe)

Valine (Val)

Proline (Pro)

Leucine (Leu)

Tryptophan (Trp)

Isoleucine (Ile)
http://www.indstate.edu/thcme/mwking/amino-acids.htm
 The simplest amino acid is Glycine, which has a single hydrogen atom as its side
chain.
Alanine, Valine, Leucine and Isoleucine have saturated hydrocarbon R groups (i.e.
they only have hydrogen and carbon linked by single covalent bonds). Leucine and
Isoleucine are isomers of each other.

Alanine Valine

Leucine Isoleucine
The side chain of Methionine includes a sulfur atom but remains
hydrophobic in nature.

Phenylalanine is Alanine with an extra benzene (sometimes called a Phenyl)

group on the end. Phenylalanine is highly hydrophobic and is found buried
within globular proteins.

Methionine Phenylalanine
Tryptophan is highly hydrophobic and tends to be found immersed inside globular
proteins.

Structurally related to Alanine, but with a two ring (bicyclic) indole group added in place of
the single aromatic ring found in Phenylalanine.

The presence of the nitrogen group makes Tryptophan a little less hydrophobic than
Phenylalanine.
Proline is unique amongst the amino acids – its side chain is bonded to the
backbone nitrogen as well as to the a-carbon.

Because of this proline is technically an imino rather than an amino acid.

The ring is not reactive, but it does restrict the geometry of the backbone chain
in any protein where it is present.
 Polar (Hydrophilic) R Groups
Serine (Ser) Cysteine (cys)

Threonine (Thr) Asparagine (Asn)

Glutamine (Gln)
Tyrosine (Tyr)

http://www.indstate.edu/thcme/mwking/amino-acids.html
Tyrosine is Phenylalanine with an extra hydroxyl (-OH) group attached.

It is polar and very weakly acidic. Tyrosine can play an important catalytic role
in the active site of some enzymes. Reversible phosphorylation of –OH group in
some enzymes is important in the regulation of metabolic pathways

Serine and Threonine play important role in enzymes which regulate

phosphorylation and energy metabolism.
Cysteine has sulfur-containing side group.The group has the potential to be
more reactive.It is not very polar.

Cysteine is most important for its ability to link to another cysteine via the
sulfur atoms to form a covalent disulfide bridge, important in the formation
and maintenance of the tertiary (folded) structure in many proteins.

COOH - CH - CH2 - HS SH - CH2- CH - COOH

NH2 NH2

S S
Asparagine and Glutamine are the amide derivatives of Aspartate (Aspartic
acid) and Glutamate (Glutamic acid) - see below. They cannot be ionised and
are therefore uncharged.

Asparagine Glutamine
Negatively (Nonpolar) Charged R Groups

Aspartic acid (Asp) Glutamic acid (Glu)

Two amino acids with negatively charged (i.e. acidic) side chains - Aspartate
(Aspartic acid) and Glutamate (Glutamic acid).

These amino acids confer a negative charge on the proteins of which they are
part.
 Positively Charged R Groups

Lysine (Lys) Arginine (Arg) Histidine (His)

Lysine and Arginine both have pKs around 10.0 and are therefore always
positively charged at neutral pH.

With a pK of 6.5, Histidine can be uncharged or positively charged depending

upon its local environment.

Histidine has an important role in the catalytic mechanism of enzymes and

explains why it is often found in the active site.
 Essential Amino Acids in Humans
Ten proteinogenic amino acids are called essential for humans
because they cannot be created from other compounds by the
human body and so must be taken in as food
Required in diet
Humans incapable of forming requisite
carbon skeleton
Arginine* Lysine
Histidine* Methionine
Isoleucine Threonine
Leucine Phenylalanine
Valine Tryptophan

* Essential in children, not in adults

 MEMORY TIP
• Any Help In Learning These Little
Molecule Proves Truly Valuable

• This stands for: Arginine, Histidine, Isoleucine,

Leucine, Threonine, Lysine, Methionine,
Phenylalanine, Tryptophan, Valine
 Non-Essential Amino Acids in Humans

• Not required in diet

• Can be formed from a-keto acids by transamination and
subsequent reactions
Alanine Glycine
Asparagine Proline
Aspartate Serine
Glutamate Cysteine (from Met*)
Glutamine Tyrosine (from Phe*)

* Essential amino acids

 Uncommon Amino Acids
Hydroxylysine and hydroxyproline, are found in the
collagen and gelatin proteins.
Thyroxin and 3,3`,5-triiodothyronine, iodinated a.a.
are found in thyroglobulin, a protein produced by the
thyroid gland.
γ-Carboxyglutamic acid is involved in blood clotting.
Finally, N-methylarginine and N-acetyllysine are found
in histone proteins associated with chromosomes.
Uncommon amino acids found in
proteins

Intermediates of biosynthesis of
arginin and in urea cycle
The two stereoisomers of alanine

a-carbon is a chiral center

Two stereoisomers are called

enantiomers.

The solid wedge-shaped bonds

project out of the plane of paper,
the dashed bonds behind it.

The horizontal bonds project out of

the plane of paper, the vertical
bonds behind.
 Optical Properties of Amino Acids

The α-carbon of a.a.

is attached to four
different chemical
groups is a chiral or
optically active carbon atom.
Glycine is the exception.
Amino acids exist in two forms, D and L, that are mirror images
of each other.
All amino acids found in proteins are of the L-configuration.
 ACIDIC AND BASIC PROPERTIES OF AMINO ACIDS

Amino acids in aqueous solution contain weakly acidic α-carboxyl

groups and weakly basic α-amino groups.

Each of the acidic and basic amino acids contains an ionizable

group in its side chain.

So, both free and some of the combined amino acids in peptide
linkages can act as buffers.

The concentration of a weak acid (HA) and its conjugate base(A-)

is described by the Henderson-Hasselbalch equation.
Buffers
Henderson/Hasselbach equation and pKa
Protonated form Unprotonated form (conjugate base)
HA H+ + A-

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

[HA]
[H+] = Ka x
[A-]

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

[A-]
pH = pKa + log
[HA]
Nonionic and zwitterion forms of amino acids
The zwitterion predominates at neutral pH

Zwitterion = in German for „hybrid ion“

Week acid

Week base
 Amino acids have characteristic titration curves

Proton Proton
donor acceptor

At the midpoint – pK=9.60 there is

+ equimolar concentration of
proton donor and proton
acceptor.

Dipolar ion Izoelectric point

+ At the midpoint – pK1=2.34 there is

equimolar concentration of proton
donor and proton acceptor.

Proton Proton
Fully protonated form donor acceptor
at wery low pH
 27.7
Peptides
 Peptides
• Peptides are compounds in which an amide
bond links the amino group of one a-amino
acid and the carboxyl group of another.
• An amide bond of this type is often referred to
as a peptide bond.
 Alanine and Glycine

H O H O
+ + –
–
H3N C C H3N C C O
O

CH3 H
 Alanylglycine

H O H O
+ –
H3N C C N C C O

CH3 H H

• Two a-amino acids are joined by a peptide

bond in alanylglycine. It is a dipeptide.
 Alanylglycine

H O H O
+ –
H3N C C N C C O

CH3 H H
N-terminus C-terminus
Ala—Gly

AG
 Alanylglycine and
glycylalanine are
constitutional isomers
H O H O
Alanylglycine
+ – Ala—Gly
H3N C C N C C O AG

CH3 H H

H O H O
Glycylalanine
+ – Gly—Ala
H3N C C N C C O GA

H H CH3
 Alanylglycine
H O H O
+ –
H3N C C N C C O

CH3 H H

• The peptide bond is

characterized by a
planar geometry.
 Higher Peptides

• Peptides are classified according to the

number of amino acids linked together.
• dipeptides, tripeptides, tetrapeptides,
etc.
• Leucine enkephalin is an example of a
pentapeptide.
Leucine Enkephalin

Tyr—Gly—Gly—Phe—Leu
YGGFL
 Oxytocin
4 5
3
Ile—Gln—Asn C-terminus

2 Tyr
Cys—Pro—Leu—GlyNH2

6 7 8 9
1 Cys S S

N-terminus

• Oxytocin is a cyclic nonapeptide.

• Instead of having its amino acids linked in
an extended chain, two cysteine residues
are joined by an S—S bond.
 Oxytocin

S—S bond

An S—S bond between two cysteines is

often referred to as a disulfide bridge.