Amino Acids

What Are the Structures and Properties of Amino

Acids, the Building Blocks of Proteins?

• Amino acids contain a central tetrahedral

carbon atom
• There are 20 common amino acids
• Amino acids can join via peptide bonds
• Several amino acids occur only rarely in
proteins
• Some amino acids are not found in
proteins
 Amino Acids
Building Blocks of Proteins

Anatomy of an amino acid. Except for proline and its derivatives, all of the
amino acids commonly found in proteins possess this type of structure.
Chemistry 40 (Summer 2007)

Amino Acids Can Join Via Peptide Bonds

The α-COOH and α-

NH3+ groups of two
amino acids can
react with the
resulting loss of a
water molecule to
form a covalent
amide bond.

Chemistry 40 (Summer 2007)

 20 Common Amino Acids

You should know names, structures, pKa

values, 3-letter and 1-letter codes

• Non-polar amino acids

• Polar, uncharged amino acids
• Acidic amino acids
• Basic amino acids

Chemistry 40 (Summer 2007)

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Several Amino Acids Occur Rarely in

Proteins

• Hydroxylysine, hydroxyproline - collagen

• Carboxyglutamate - blood-clotting proteins
• Pyroglutamate – in bacteriorhodopsin
• Phosphorylated amino acids – a signaling
device
The structures of
several amino acids
that are less common
but nevertheless found
in certain proteins.
Hydroxylysine and
hydroxyproline are
found in connective-
tissue proteins,
pyroglutamic acid is
found in
bacteriorhodopsin (a
protein in
Halobacterium
halobium), and
aminoadipic acid is
found in proteins
isolated from corn.
Chemistry 40 (Summer 2007)

The structures
of some amino
acids that are
not normally
found in
proteins but that
perform other
important
biological
functions.
Epinephrine,
histamine, and
serotonin,
although not
amino acids,
are derived
from and
closely related
to amino acids.
Chemistry 40 (Summer 2007)
 What Are Acid-Base Properties of Amino
Acids?

• Amino Acids are Weak Polyprotic Acids

• H2A+ + H2O
HA0 + H3O+

• Ka1 = [ HA0] [ H3O+ ]

[H2A+ ]

The second dissociation (the amino group in

the case of glycine):

• HA0 + H2O → A¯ + H3O+

• Ka2 = [ A¯ ] [ H3O+ ]
[ HA0 ]
The ionic forms of the amino acids, shown without consideration of any ionizations on
the side chain. The cationic form is the low pH form, and the titration of the cationic
Chemistry
species with base yields the zwitterion and40 finally
(Summer 2007)
the anionic form.

pKa Values of the Amino Acids

• Alpha carboxyl group - pKa = 2

• Alpha amino group - pKa = 9
 pKa Values of the Amino Acids

• Arginine, Arg, R: pKa(guanidino

group) = 12.5
• Aspartic Acid, Asp, D: pKa = 3.9
• Cysteine, Cys, C: pKa = 8.3
• Glutamic Acid, Glu, E: pKa = 4.3
• Histidine, His, H: pKa = 6.0

pKa Values of the Amino Acids

• Lysine, Lys, K: pKa = 10.5

• Serine, Ser, S: pKa = 13
• Threonine, Thr, T: pKa = 13
• Tyrosine, Tyr, Y: pKa = 10.1
Titration of glycine, a simple
amino acid. The isoelectric
point, pI, the pH where the
molecule has a net charge of
0, is defined as (pK1+ pK2)/2.

Chemistry 40 (Summer 2007)

Titration of glutamic acid.

Chemistry 40 (Summer 2007)

Titration of lysine.

Chemistry 40 (Summer 2007)

A Sample Calculation

What is the pH of a glutamic acid solution

if the alpha carboxyl is 1/4 dissociated?

•pH = 2 + log10 [1]

[3]
•pH = 2 + (-0.477)
•pH = 1.523
 Another Sample Calculation
What is the pH of a lysine solution
if the side chain amino group is
3/4 dissociated?

• pH = 10.5 + log10 [3]

[1]
• pH = 10.5 + (0.477)
• pH = 10.977 = 11.0

Reactions of Amino Acids

• Carboxyl groups form amides & esters
• Amino groups form Schiff bases and
amides
• Side chains show unique reactivities
– Cys residues can form disulfides and
can be easily alkylated
– Few reactions are specific to a single
kind of side chain
The pathway of the
ninhydrin reaction,
which produces a
colored product
called “Ruhemann’s
Purple” that absorbs
light at 570 nm. Note
that the reaction
involves and
consumes two
molecules of
ninhydrin.

Chemistry 40 (Summer 2007)

Stereochemistry of Amino Acids

• All but glycine are chiral

• L-amino acids predominate in nature
• D,L-nomenclature is based on D- and L-
glyceraldehyde
• R,S-nomenclature system is superior,
since amino acids like isoleucine and
threonine (with two chiral centers) can be
named unambiguously
Enantiomeric molecules based
on a chiral carbon atom.
Enantiomers are
nonsuperimposable mirror
images of each other.

Chemistry 40 (Summer 2007)

The configuration of the

common L-amino acids
can be related to the
configuration of L(-)-
glyceraldehyde as shown.
These drawings are
known as Fischer
projections. The horizontal
lines of the Fischer
projections are meant to
indicate bonds coming out
of the page from the
central carbon, and
vertical lines represent
bonds extending behind
the page from the central
carbon atom.
Chemistry 40 (Summer 2007)
 The stereoisomers of isoleucine and threonine. The
structures at the far left are the naturally occurring isomers.
Chemistry 40 (Summer 2007)

The assignment of (R) and (S) notation for glyceraldehyde and

Chemistry 40 (Summer 2007)
L-alanine .
 Spectroscopic Properties
• All amino acids absorb at infrared
wavelengths
• Only Phe, Tyr, and Trp absorb UV
• Absorbance at 280 nm is a good
diagnostic device for amino acids
• NMR spectra are characteristic of each
residue in a protein, and high resolution
NMR measurements can be used to
elucidate three-dimensional structures of
proteins

Chemistry 40 (Summer 2007)

 Separation of Amino Acids

• Mikhail Tswett, a Russian botanist, first

separated colorful plant pigments by
‘chromatography’
• Many chromatographic methods exist for
separation of amino acid mixtures
– Ion exchange chromatography
– High-performance liquid
chromatography

Cation (a) and anion (b)

exchange resins commonly
used for biochemical
separations.

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