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Amino Acids
Pn Khadijah Hanim Abdul Rahman
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
Amino acids shown
in their prevailing
ionic forms at pH7,
approx pH within a
Name and three-letter
abbreviation of amino acid
The exception : proline differ from other
standard amino acid
Its amino group is secondary
Formed by ring closure between R group and
the amino nitrogen
Standard amino acid
(primary amino group)
Proline (secondary amino group)
Amino acid structure
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)
Neutral molecules which bear an equal number
of positive and negative charges
simultaneously are called zwitterions
The R group give each amino acid its unique
Structure of amino acid at pH7
Amino acid classes
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 (Gly, Ala, Val, Leu, Ile,
Phe, Trp, Met, Cys, Pro)
b) neutral polar (ser, thr, tyr, asn, gln)
c) acidic (Asp, glu)
d) basic (lys, arg, his)
a) Neutral nonpolar amino acids
Term‘Neutral’ – contains hydrocarbon 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 proteins
2 types of hydrocarbon R groups:
a) aromatic (contain cyclic structure that
constitute a class of unsaturated hydrocarbons)
eg. Phenylalanine, tryptophan
b) aliphatic (nonaromatic hydrocarbon)
eg. Glycine, alanine, valine, leucine,
isoleucine, proline, methionine, cysteine
Methionine & cysteine contain sulfur atom in
the aliphatic side chain
In met, the nonbonding electrons of the sulfur
atom can form bonds with electrophiles such as
metal ions.
The nonpolar sulfhydryl group (-SH) of cys can
form a weak H bond with O or N.
Sulfhydryl groups are highly reactiveimportant component in many enzymes.
b) Neutral polar amino acids
Polar amino acids = hydrophilic (water loving)
Have functional group capable of forming
hydrogen bonding, so easily interact with water
Serine, threonine, tyrosine, asparagine,
Serine, threonine, tyrosine
- contain polar hydroxyl group (-OH)
- Thus enable them to from hydrogen bonding
(important factor in protein structure)
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
c) Acidic amino acids
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
Lysine, Arginine, Histidine
Are polar and positively charge at physiological pH.
Therefore can form ionic bonds with acidic amino
Lys contain amine R group which accepts a proton
from water to form conjugate acid (-NH3+)
His is a weak base because it partially ionized at pH
7. His act as buffer. Important role in catalytic
activity of enzymes.
Biologically active amino acids
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
Metabolite intermediates
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
(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
- a compound that participate in the chemical
reaction to produces another compound
- amino acids are precursors of variety of
complex nitrogen-containing molecules
- Nitrogenous base components of nucleotides
and nucleic acids, chlorophyll
Metabolic intermediates
- several amino acids act
as metabolic
- eg. Arginine, citrulline,
ornithine (components of
urea cycle)
- The synthesis of urea, a
molecule formed in the
livers- principle
mechanism for disposal
of nitrogenous waste
Amino acid stereoisomers
α-carbon of 19 amino acids
attached to 4 diff. groups, referred
as asymmetric/chiral carbons
Molecule with chiral carbon, can
exist as stereoisomers
- isomeric molecule that have the
same molecular formula
- but differ only in the threedimensional orientations of their
atoms in space.
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
Glyceraldehyde is the reference compound for
optical isomers (to differ between L and D)
Most asymmetric molecules found in living
organisms only occur in only 1 stereoisomeric form,
either D or L.
Chirality has had a profound effect on the structural
and functional properties of biomolecules
For eg: the right-handed helices result from the
presence of L-amino acids.
In addition, because enzymes are chiral molecules,
they only bind substrate molecules in one
enantiomeric form.
Proteases, enzyme that degrade proteins by
hydrolyzing peptide bonds, cannot degrade
polypeptides composed of D-amino acids.
Certain bacterial species have outer layers
composed of polymers made of D-amino
acids. Immune system cells, whose task is to
attack and destroy foreign cells, cannot destroy
those bacteria. Suggest a reason for this
Titration of amino acids
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
- a useful tool in determining the reactivity of
amino acid side chains
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)
+ HCl +H3N-CH2-COOH + Cl(base)
+ NaOH H2N-CH2-COO- + Na+ +H2O
Titration of alanine
Consider alanine, a simple amino acid contain
2 titrable groups
During titration with strong base, NaOH,
alanine loses 2 protons.
In a strongly acidic sol (pH 0), ala present
mainly in the form of in which the carboxyl
group is uncharged.
At this point, glycine net charge = +1, because
ammonium group is protonated.
Lowering of the H+ conc results in the COOH group
losing a proton to become COO-.
At this point, ala has no net charge and electrically
The pH at which this occur is called the isoelectric
point (pI)
Because no net charge at pI, amino acids are least
soluble at this pH.
The pI for ala may be calculated as: pI = pK1 + pK2
pK1 and pK2 of glycine are 2.34 and 9.7.
The pI value for glycine :
pI = 2.34 + 9.7 = 6
As the titration continues, the ammonium group
will lose its proton, leaving an uncharged amino
This molecule has a net –ve charge because of
the carboxylate group.
Titration of glutamic acid with
Amino acids with ionizable side chains
(acidic & basic a.a) have more complex
titration curve.
For eg. Glutamic acid has a carboxyl side
chain group (R group)
At low pH, glutamic acid has net charge +1.
As base added, the a-carboxyl group loses a
proton to become carboxylate group. Glutame
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, results in the ammonium
ion loses its proton
 At this point, glutamate has a net charge of -2
 The pI value for glutamate is the pH halfway
between the pKa values for the two carboxyl
pI = 2.19 + 4.25 = 3.22
 pI is the pH at which amino acid has a net
charge zero.
 For acidic amino acids
pI = pK1 + pK2
 For basic amino acids :
pI = pK2 + pK3
Amino acid reactions
The functional groups of organic molecules
determine which reactions they may undergo.
Amino acids with their COOH groups, amino
groups and various R groups can undergo
numerous chemical reactions.
i.e peptide bond & disulfide bridge formation
(effect protein structure)
Peptide bond formation
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
This reaction is a dehydration (mol. water is
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
As amino acids are added and the chain
lengthens, the prefix reflect the number of
eg. Tripeptides contain three amino acid
Peptide bonds
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
Peptides are named by using their amino acid sequence,
start from their N-terminal residue
eg. Alanylglycylphenilalanine
Cysteine oxidation
The sulfhydryl group of cysteine is highly
Common reaction = reversible oxidation that
form disulfide
Two molecules of cysteine oxidized to form a
cystine (molecule that contain disulfide bond)
When 2 cys residues form such bond, it is
referred to as a disulfide bridge.
Disulfide bridges help to stabilize many
polypeptides and proteins.