ERT 106 BIOCHEMISTRY
Amino Acids
Pn Syazni Zainul Kamal
Introduction
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Proteins - the most structural, sophisticated
molecules known
- vary extensively in structure
- are polymer constructed from the
same set of 20 amino acids
Polymer of amino acids = polypetides
Proteins consists of 1 or more polypeptides
folded and coiled into specific conformations
Amino Acids structure
Amino Acids contain a central carbon atom (α-carbon) to
which an amino group, a carboxylate group, a hydrogen
atom and an R (side chain) group are attached
Structure of amino acids commonly found in
protein
Amino acids shown in their prevailing ionic forms at pH7, approx pH within a cell
Name and three-letter
abbreviation of amino acid
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The exception : proline differ from other
standard amino acid
R group makes up part of a ring which also
includes the amino group and the α-carbon
atom.
Since the amino group in proline is involved in
two carbon-nitrogen bonds, it is a secondary
amino group.
Standard amino acid
(primary amino group)
Proline (secondary amino
group)
Amino acid structure
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The amino and carboxylic groups of amino acids
readily ionized
At physiological pH (7)
- carboxyl group of an amino acid is unprotonated.
conjugate base form (-COO-)
- amino group of an amino acid is protonated. in its
conjugate acid form (+NH3)
Thus, each amino acid can behave as an acid or base
referred as amphoteric (substance that can act as acid
or base)
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Neutral molecules which bear an equal umber
of positive and negative charges
simultaneously are called zwitterions
The R group give each amino acid its unique
properties
Structure of amino acid at pH7
Amino acid classes
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Sequence of amino acids determines the threedimensional configuration of each protein
Amino acids classified based on their capacity
to interact with water
4 classes of amino acids :
a) neutral nonpolar
b) neutral polar
c) acidic
d) basic
a) Neutral nonpolar amino acids
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Term‘Neutral’ – R groups do not bear +ve or
–ve charge
So they interact poorly with water and play
important role in maintaining the threedimensional structure of protein
Contain hydrocarbon R groups
2 types of hydrocarbon R groups:
a) aromatic (contain cyclic structure)
eg. Phenylalanine, tryptophan
b) aliphatic (nonaromatic hydrocarbon)
eg. Glycine, alanine, valine, leucine,
isoleucine, proline, methionine, cysteine
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Methionine & cysteine contain sulfur atom in
the aliphatic side chain
b) Neutral polar amino acids
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Polar amino acids = hydrophilic (water loving)
Have functional group capable of forming
hydrogen bonding, so easily interact with water
Serine, threonine, tyrosine, asparagine,
glutamine
Serine, threonine, tyrosine
- contain polar hydroxyl group (-OH)
- Thus enable them to from hydrogen bonding
(important factor in protein structure)
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Asparagine & glutamine
- are amide derivatives of aspartic acid and
glutamic acid (acidic amino acids)
- amide funtional group are highly polar, so
can form hydrogen bonding (effet on protein
stability)
c) Acidic amino acids
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Contain carboxylate R group
The side chains of aspartic acid & glutamic
acid are polar and negatively charged at
physiological pH, so they often referred as
aspartate and glutamate
d) Basic amino acids
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Lysine, Arginine, Histidine
Contain amine R group
Are polar and positively charge at
physiological pH
Can form ionic bond with acidic amino acids
Very hydrophilic
Biologically active amino acids
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1)
2)
3)
The 20 standard amino acids undergo a bewildering
number of chemical transformations.
Many amino acids are synthesizes not to be residues
of polypeptides but to function independently.
Besides being components of protein, amino acids
have several biological roles :
Chemical messengers
Precursors
Metabolite intermediates
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Chemical messengers
- Neurotransmitters = substances released from
one nerve cell that influence the function of a
second nerve cell or a muscle cell
- Glycine
- γ-amino butyric acids (GABA)
(derivative of glutamate),
- serotonin & melatonin
(derivative of tryptophan)
- Hormones = chemical signal molecules
produced in one cell that regulate the function
of other cells
- Thyroxine (tyrosine derivative), thyroid
hormon secreted by thyroid gland
- Indole acetic acid (tryptophan derivative), is
an auxin plant hormones. Stimulate growth of
the root and shoot
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Precursors
- a compound that participate in the chemical
reaction to produces another compound
- amino acids are precursors of variety of
complex nitrogen-containing molecules
- eg. Nucleotides, nucleic acids, chlorophyll
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Metabolic intermediates
- several amino acids act as metabolic
intermediates
- eg. Arginine, citrulline, ornithine
(components of urea cycle)
Amino acid stereoisomers
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α-carbon of 19 amino acids
attached to 4 diff. groups, referred
as asymmetric/chiral carbons
Molecule with chiral carbon, can
exist as stereoisomers
Stereoisomers
- isomeric molecule that have the
same molecular formula
- but differ only in the threedimensional orientations of their
atoms in space.
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Molecules with chiral carbon are not superimposable
on their mirror image in the same way that a left hand
is not superimposable on its mirror image, a right hand
They are known as enantiomers of one another
L-Alanine and D-Alanine are mirror image to one another
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Glyceraldehyde is the reference compound for
optical isomers (to differ between L and D)
Titration of amino acids
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Amino acids contain ionizable group, the
predominant ionic form of amino acids in
solution depends on pH
Titration of amino acid :
- illustrate the effect of pH on amino acids
structure
- a useful tool in determining the reactivity of
amino acid side chains
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when amino acid is dissolved in water, it
exist predominantly in the isoelectric form
Upon titration with base, it act as an acid
(donate proton)
Upon titration with acid, it act as a base
(accept proton)
eg. titration of glycine with NaOH
(base)
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Glycine has two titratable (ionizable) groups :
carboxyl group & ammonium group
+NH -CH -COO3
2
Upon titration with base, glycine loses two protons
At pH0 (acidic) – glycine is present in the form which
carboxyl group is uncharged
+NH -CH -COOH
3
2
At this point, glycine net charge = +1, because
ammonium group is protonated
Gly +
Gly 0
Gly -
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As the pH increase, carboxyl group losing its
proton to become a negatively charged
carboxylate group
+NH -CH -COO3
2
At this point, glycine has no net charge and is
electrically neutral.
The pH at which this occurs is called the
isoelectric point (pI).
Isoelectric point of glycine may be calculated as
pI = pK1 + pK2
2
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pK1 and pK2 of glycine are 2.34 and 9.6.
The pI value for glycine :
pI = 2.34 + 9.6 = 5.97
2
As the titration continues, the ammonium group
will lose its proton, leaving an uncharged amino
group
NH2-CH2-COO-
eg. Titration of glutamic acid with
NaOH
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Amino acids with ionizable side chains
(acidic & basic a.a) have more complex
titration curve.
eg. Glutamic acid has a carboxyl side chain
group
At acidic pH (eg. pH0), carboxyl groups are
uncharged
Glutamic acid net charge = +1
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As base is added, α-carboxyl group loses a
proton to become a carboxylate group
Glutamate now, has no net charge
As more base added, the 2nd carboxyl group
(side chain) loses a proton
The molecule now has a net charge of -1
Adding more base, ammonium ion loses its
proton
At this point, glutamate has a net charge of -2
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The pI value for glutamate is the pH halfway
between the pKa values for the two carboxyl
group
pI = pK1 + pK2
2
Note:
 pI is the pH at which amino acid has a net
charge zero.
 For acidic amino acids
pI = pK1 + pK2
2
 For basic amino acids :
pI = pK2 + pK3
2
Amino acid reactions
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Amino acids with their carboxyl group, amino
group and various R group can undergo
numerous chemical reaction
i.e peptide bond & disulfide bridge formation
(effect protein structure)
Peptide bond formation
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Polypeptides are linear polymers composed of
amino acids linked together by peptide bonds
Peptide bonds are amide linkage (CO-NH)
formed when the carboxyl group of one amino
acid react with amino group of another amino
acid
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This reaction is a dehydration (mol. water is
removed)
So, the linked amino acids are referred to as
amino acid residues.
When two amino acid molecules are linked, the
product is called a dipeptide.
eg. Serine and glycine can form dipeptides
glycylserine or serylglycine
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As amino acids are added and the chain
lengthens, the prefix reflect the number of
residues
eg. Tripeptides contain three amino acid
residues
Amino acid residue with the free amino group
is called the N-terminal residue and is written
to the left
Amino acid residue with free carboxyl group is
called C-terminal residue and is written to the
right
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eg.
Peptides are named by using their amino acid sequence,
start from their N-terminal residue
eg. Alanylglycylphenilalanine
Cysteine oxidation
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The sulfhydryl group of cysteine is highly
reactive
Common reaction = reversible oxidation that
form disulfide
Two molecules of cysteine oxidized to form a
cystine (molecule that contain disulfide bond)