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Lecture 2
Amino acids
Function of amino acids
• Amino acids are critical to life, and
have a variety of roles in metabolism.
– One particularly important function is as
the building blocks of proteins
– forming parts of coenzymes
– as precursors for the biosynthesis of
molecules such as heme
History
• The 1st AA(asparagine, Asp) was
discovered in 1806 from asparagus (a
green vegetable).
• The last (threonine, Thr) was not
identified until 1938!
Standard and nonstandard amino acids
• Standard -amino acids: Although more
than 300 different amino acids have been
described in nature, only 20 are commonly
found as constituens of mammalian proteins.
•
Nonstandard amino acids: less common AAs
modified after a protein has been
synthesized, and many other kinds of AAs
present in living organisms but not in
proteins.
1. General structure of -amino acids
(Very important!)

• Each has a carboxyl
group and an amino
group bonded to the
same -carbon atom.
• Each has a different
side chain (or R group,
R=“Remainder of the
molecule”).
R group
Greek letter nomenclature is used in protein
chemistry.
2. Stereochemistry of AA
2.1 Configuration
For all the common amino acids
except Gly, the α-carbon is bonded
to four different groups. The αcarbon atom is thus a chiral center.

Handedness
• Chiral: An object or
a system is chiral if
it cannot be
superimposed on its
mirror image.
• One hand does not
match the other
when superimposed.
Molecular Handedness
• Chiral molecule: if a
molecule has an atom
bonded to four
different groups, it
can be chiral.
• Chiral carbon atom
(chirality center): A
carbon atom bonded to
four different groups.
Enantiomers: a chiral molecule, has
left- and right-handed isomers,
called enantiomers or optical isomers.
2.2 Optical activity of AAs
• Chiral molecules have optical activity.
• The two enantiomers of each AA are
designated by D,L system.
– D: Dextrorotation
– L: Levorotation
• D- and L-forms of AAs are named in
reference to the absolute configuration
of D- and L- glyceraldehydes.
Enantiomers
•Lined up by similarity: chiral to chiral, COO- to CHO
•Only the L-amino acids have been found in proteins
(D-isomers have been found only in small peptides of
bacteria cell walls and in some peptide antibiotics).
3. The Classification of Amino Acids
(very important!!!)
• The name and abbreviation of AAs
– All the AAs were given a trivial (common) name.
Glutamate from wheat gluten (sticky). Tyrosine
from cheese (“tyros” in Greek).
– Each AA is given a 3 letter abbreviation and 1
letter symbol. (They often the first three
letter and the first letter. When there is
confusion, an alternative is used).
• They should be remembered !
Classification of Amino Acids
• Classification of amino acids based on
polarity
– Nonpolar, aliphatic amino acids
– Aromatic amino acids: Amino acids with aromatic
“R” group
– Polar amino acids with uncharged “R” group
– Basic amino acids: Polar amino acids with
positive “R” group
– Acidic amino acids: Polar amino acids with
negative “R” group
3.1 Amino acids with nonpolar, aliphatic
(hydrophobic) R groups
Gly, G
Ala, A
Pro, P
Val, V
Leu, L
Ile, I
Met, M
• Gly has a hydrogen as its R group, having
minimal steric hindrance.
•Glycine is symmetric and has no chirality.
 Pro has an imino group, instead of an amino
group, forming a five-membered ring structure,
being rigid in conformation.
Ala, Val, Leu, Ile and Met, have hydrocarbon
R groups, often involved in hydrophobic
interactions for stabilizing protein structure .
3.2 Amino acids with aromatic side chains
• They are Phe, Tyr and Trp.
 Phe and Tyr both have benzene rings.
Tryptophan has an indole ring.
Phe, F
Tyr, Y
Trp, W
• The -OH group in Tyr is an important functional
group in proteins. (phosphorylation, hydrogen bond,
etc), polar
• They are jointly responsible for the light
absorption of proteins at 280 nm.
•Proteins in solution
absorb ultraviolet
light with
absorbance
maximum at 280nm.
λmax= 280nm, for
measuring protein
content by
photospectrometry
Absorbance of ultraviolet light by Tyr and Trp
3.3 Amino acids with uncharged polar side chains
 They are Ser, Thr, Cys, Asn, and Gln .
Ser, S
Thr, T
Cys, C
Asn, N
Gln, Q
• Their R groups
are more
hydrophilic, due
to the presence
of hydroxyl
groups, sulfur
atoms or amide
groups which may
form hydrogen
bonds with water.
Disulfide bonds
-SH group of two Cys in proteins can be oxidized
to form a covalent disulfide bond.
 Disulfide bonds play a special role in the
structures of many proteins by forming covalent links
between parts of a protein molecule or between two
different protein chains.
disulfide
bond
3.4 Amino acids with acidic side chains
• They are Asp and Glu. Both have carboxyl
in their R groups.
•They have net
negative charge
at pH 7.0, thus
usually named as
aspartate and
glutamate
(conjugate base
names, instead of
aspartic acid and
glutamic acid, unionized form).
Asp, D; Glu, E
3.5 Amino acids with basic side chains
 They are Lys, Arg, and His. All have
positively charged R groups at pH 7.0.
Their R
groups
contain
amino,
guanidino,
imidazole
groups
respectively.
K
R
H
• Note these structural features
1. All 20 are -amino acids
2. For 19 of the 20, the -amino group is
primary; for proline, it is secondary
3. With the exception of glycine, The  carbons for 19 of them are asymmetric
(or chiral).
• Nonpolar Amino Acids
Ala Val Leu Ile Gly Pro Met Phe Trp
• Polar,Uncharged Amino Acids
Ser Thr Cys Asn Gln Tyr
• Acidic Amino Acids Asp Glu
• Basic Amino Acids
Lys Arg His
Aromatic
3.6 Nonstandard amino acids
• Some nonstandard amino acids are
found in certain proteins, generally as
a result of modifications which are
made after the standard amino acids
have been incorporated into proteins.
( post-translational modifications).
• 4-Hydroxyproline
and 5-hydroxylysine
in collagen.
 6-N-Methyllysine
in myosin.
Many additional nonstandard amino acids
are found in cells, but not in proteins
(e.g., ornithine and citrulline,
intermediates in amino acid metabolism).
3.7 Essential and non-essential amino acid
• Essential amino acid (or indispensable amino
acid): an amino acid that cannot be
synthesized de novo by the organism (usually
referring to humans), and therefore must be
supplied in the diet.
– 8: Phe, Val, Thr, Trp, Ile, Met, Leu, Lys
– Semi-essential amino acid: 2, His and Arg are
required by infants and growing children.
4. Properties of amino acids
• Solubility: Most of them are soluble in
water and insoluble in organic solvents.
• Taste: sweet (Gly,Ala,Val), tastless
(Leu) or bitter (Arg,Ile).
– Monosodium glutamate (MSG) is used as a
flavoring agent in food industry.
Acid/base properties of AAs
(Very important!)
• An amino acid has both a basic amine group and an
acidic carboxylic acid group.
• 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.
This is called a zwitterion (German for “hybrid ions”).
 The zwitterionic form of AAs are ampholytes.
Ampholytes are
molecules that contain
both acidic and basic
groups and will exist
mostly as zwitterions in
a certain range of pH.
• AAs can act both as acids and bases.
• The AAs ionize to various states depending on
pH values.
• There is a specific pH (designated isoelectric
point, pI) at which an AA has equal positive and
negative charge (no net electric charged) . Very
important!!!
-H+
R—CH—COOH
|
NH3+
pH<pI
+H+
-H+
R—CH—COO|
NH3+
pH=pI
+H+
R—CH—COO|
NH2
pH>pI
A+
A0
A-
cation
zwitterion
anion
• In addition,
the side chains
of some of the
amino acids
contain
ionizable groups.
pKa Values of Polyfunctional Amino Acids
Amino Acid
α-CO2H
pKa1
α-NH3 Side Chain
pKa
pKa3
2
pI
Arginine
2.1
9.0
12.5
10.8
Aspartic
Acid
2.1
9.8
3.9
3.0
Cysteine
1.7
10.4
8.3
5.0
Glutamic
Acid
2.2
9.7
4.3
3.2
Histidine
1.8
9.2
6.0
7.6
Lysine
2.2
9.0
10.5
9.8
Tyrosine
2.2
9.1
10.1
5.7
5. Chemical properties of the amino acids
• Reaction with ninhydrin
•The free - amino group of any amino acids
will react with ninhydrin to form a purple
product.
•
Detects amino acids nonspecifically.
•
The imino group of Pro gives a
yellow color.
The Ninhydrin Reaction
• A useful color
test for these
amino acids.
• A common
application of the
ninhydrin test is
the visualization
of amino acids in
paper
chromatography
6. Polypeptides
• In 1902, Emil Fischer proposed that
proteins are long chains of amino acids
joined by amide bonds to which he gave
the name peptide bonds.
– Peptide bond: the special name given to the
amide bond between the -carboxyl group
of one amino acid and the -amino group of
another.
• a condensation
reaction where a
water molecule
is liberated or
eliminated.
residue
peptide bond
• all units of a peptide chain are amino acid
residues.
The condensation reaction can occur
repeatedly to form oligopeptides,
polypeptides, and proteins .
• Short polymers of amino acids
– 2 residues - dipeptide
– 3 residues - tripeptide
– 12~20 residues - oligopeptide
• many - polypeptide
Characteristics of the peptide bond
• Lack of rotation around the bond
– The peptide (amide) bond was found to
be about 0.132nm (C-N single bond,
0.149nm; C=N double bond, 0.127nm),
thus having partial double bond feature
(i.e. rigid and unable to rotate freely).
O
C
C
C
N
H
The peptide bond is planar, trans
configuration and uncharged.
The six atoms attached to the peptide bond
are coplanar with the oxygen and hydrogen
atom in trans positions ( an exception is Pro ).
This plane is called peptide plane.
The peptide chain is directional.
The end having a free -amino group is called aminoterminal or N-terminal.
 The end having a free -carboxyl group is called
carboxyl-terminal or C-terminal.
 By convention, the N-terminal is taken as the beginning
of the peptide chain, and put at the left (C-terminal at
the right).
Naming of peptides
- Begin from the N terminal.
- Drop “-ine”,”-an”,or”-ate” and replaced by “yl”.
- Give the full name of amino acid at the C
terminal.
O
O
O
+
-
H3N-CH-C-NH-CH2-C-NH-CH-C-O
CH3
From alanine From glycine
alanyl
glycyl
CH2OH
From serine
serine
Alanylglycylserine
(Ala-Gly-Ser)
Biologically important peptides
• Glutathione (GSH)
• Tripeptide: glutamic acid, cysteine and
glycine;
• widely in plant and animal tissues;
• Function: reduced and oxidized forms
important in biological oxidation-reduction
reactions.
Glycine
Cysteine
Glutamic acid
reduced form
GSH
• oxidized form glutathione
disulfide (GSSG)
Glutathione (GSH)
• It's the most important molecule you need
to stay healthy and prevent disease.
• It’s the mother of all antioxidants, the
master detoxifier and maestro of the
immune system.
• The good news: your body produces its own
glutathione.
• The bad news: poor diet, pollution, toxins,
medications, stress, trauma, aging,
infections, and radiation all deplete your
glutathione.
Points
• General structure of -amino acids
• Chiral, D- and L-forms of AAs
• The Classification of Amino Acids
– Nonpolar, aromatic, uncharged polar, acidic and
basic side chains
•
•
•
•
Essential amino acid
Zwitterion, pI
Characteristics of the peptide bond
Glutathione (GSH)