The Amino Acids

Building Blocks of Proteins

Bryant Miles

• Every amino acid has an amino group and a

carboxylic acid group. D-Amino acids have the
amino group and the carboxylic acid group attached
to the alpha carbon atom, CD.
• There are 20 amino acids found in all proteins. Each
of the twenty amino acids has its own distinct R
group.
• The pKa’s of the D -carboxylic acids are around 2.2,
and the pKa’s of the D -amino groups are around
9.4. Therefore, at a pH above 3.5 the carboxylic
acids are entirely in their carboxylate form. The
Damino groups are entirely in the ammonium ion
form below pH 8.0.
• Because amino acids can function as both an acid
and a base, they are said to be amphoteric.

I. The nonpolar amino acids

 • Meet the nonpolar, aliphatic amino acids. They lack polar functional groups but function as the
brick and mortar of protein stability with their hydrophobic interactions.
• Glycine Gly G
Glycine is the only achiral amino acid. Glycine has the conformational flexibility.
• Alanine Ala A
• Valine Val V
• Leucine Leu L
• Methionine Met M
Met has a thioether side chain but still is nonpolar and hydrophobic.
• Isoleucine Ile I
isoleucine has a second chiral center.
• Proline Pro P
Proline is unique in that it is a cyclic secondary amino acid. Proline has the least
conformation flexibility. It is rigid.

II. The Aromatic Amino Acids

• Phenylalanine Phe F Nonpolar

• Tyrosine Tyr Y has phenolic group. Ionizable side chain, pKa = 10.5.
• Tryptophan Trp W Nonpolar and bulky, indole side chain.

• The three aromatic amino acids all absorb UV

light. Phenylalanine absorbs at 260 nm, while
tyrosine and tryptophan both absorb at 280 nm.
III. Basic Amino Acids
•Lysine Lys K
butyl ammonium side chain, pKa 10.5
• Arginine Arg R
guanidino group at the end its side
chain, pKa 12.5
• Histidine His H
imidazole group after the methylene,
pKa 6.0.
The only side chain with a pKa near physiological pH.

IV. Acidic Amino Acids

x Aspartate Asp D
pKa side chain = 3.9

• Glutamate Glu E
pKa side chain = 4.1

V. Polar, Uncharged Amino Acids

x Serine Ser S
• Threonine Thr T
Serine and threonine have hydroxyl functional groups.
• Cysteine Cys C
Cysteine has sulfhydryl side chain that can be oxidized to
form disulfide bonds.
pKa of cysteine side chain = 8.4
• Asparagine Asn N
Asparagine is the amide of aspartic acid.
• Glutamine Gln Q
Glutamine is the amide of glutamic acid.
Cysteines Often Form Disulfide Bonds.

• The disulfude bond is of great importance in protein structure. It can join two separate protein
chains or cross link two cysteines within the same chain.

VI. The Acid/Base Chemistry of Amino Acids.

• All of the Amino acids are weak polyprotic acids.
Each has ionizable groups whose degree of
ionization depends on the pH of the solution.
• The titration curves of amino acids can be
analyzed with the Henderson-Hasselbach
equation.
pH = pKa + log([A-]/[AH]
• Let’s look at glycine.
o At pH values below the pKa of the carboxylic
acid, the net charge on the glycine is +1.
o At the pKa of the carboxylic acid (2.34), the
concentrations of the carboxylic acid and the
carboxylate are equal.
o After 1 equivalent of -OH, all of the carboxylic
acid has been converted to the carboxylate. The
net charge is then 0.
o At the pKa for the ammonium group (9.6), the
concentrations of the ammonium ion and the
amine are equal.
o After 2 equivalents of base have been added all of the ammonium group has been converted to the
amine. The glycine then carries a -1 net charge.
The isoelectric point, pI.

• The pH at which the amino acid has no net charge is called the isoelectric point.
• To calculate the pI, you must determine which two pKa’s the neutral species is between and then
use the following formula.
pI = ½(pK1 + pK2)
Let us take glycine for an example. As shown in the previous figure, the isoelectric point lies
between the pKa of the carboxylic acid (2.34) and the pKa of the ammonium group (9.60).
pI = ½(2.34 + 9.60) = 5.97

The titration of glutamic acid

• Glutamic acid has three ionizable groups. The
pKa of the D-carboxylic acid is 2.2, The pKa
of the side chain carboxylic acid is 4.3. The
pKa of the ammonium group is 9.7.
• At low pH, glutamic acid is fully protonated
which a net charge of +1
• As the pH is increased, the D-carboxylic acid,
is titrated as it has the lowest pKa.
• After 1 equivalent of base has been added, all
of the D-carboxylic acid is converted to the D-
carboxylate. The net charge is 0.
• Next the side chain carboxylic acid is titrated.
After another 1 equivalent of base, all of the
side chain carboxylic acid has been converted
to the carboxylate. The net charge is -1.
• Finally the ammonium group is titrated, after
yet another equivalent of base (3 total), all of
the ammonium group has been converted to
the amine. The net charge is -2.
• The isoelectric point falls between the pKa’s of the two carboxylic acids so the pI is calculated as:
• pI = ½(2.2 +4.3) = 3.3

The Titration of Histidine

• Similarly, Histidine can be titrated.
• At low pH histidine is fully protonated with a net charge of +2.
• After one equivalent of base has been added, all of the carboxylic acid has been titrated to the
carboxylate ion. The net charge is +1.
• After another equivalent of base has been added, all of the imidazolium ion has been titrated to
imidazole. The net charge is 0.
• After the third equivalent of base has been added all of the ammonium ion has been titrated to the
amine. The net charge is a -1.
• The isoelectric point falls between the pKa of the imidazolium ion and the pKa of the ammonium
group, so the pI calculation is,
• pI = ½(6.0 + 9.3) = 7.65
Titration of Lysine
• Similar to Histidine, the titration of
lysine is shown here.

• The isoelectric point falls between the

ionizations of the two ammonium
groups.

• pI = ½(9.1 + 10.5) = 9.8

VII. Stereochemistry

D,L-System
• The D,L system compares the configuration of a chiral molecule to that of glyceraldehyde.
• L-glyceraldehyde rotates planes of polarized light in the levorotary or left direction.
• D-glyceraldehyde rotates planes of polarized light to the dextrorotary or right direction.
• The glyceralde enantiomer shown on the left is L-glyceraldehyde.
• The enantiomer of the right is the D-glyceraldehyde.

L-Amino Acids

L-Glyceraldehyde L-Amino Acid

» All D-amino acids found in proteins have the L stereochemistry.

R,S System

• The order of priority for the R/S system is SH>OH>COOH>CHO>CH2OH>C6H5>CH3>H

• To establish the configuration of the chiral center, it is viewed from the asymmetric center towards
the group of lowest priority, in this case the hydrogen. If the order of priority of the remaining
three groups is clockwise, then its designated R, if the order of priority of the three groups is
counter clockwise, then it is designated S.
• When applied to all 19 of the chiral amino acids (glycine is achiral), all are S except for cysteine
because the CH2SH group has priority over the COOH. L-Cysteine is (R) Cysteine.

Peptide Bonds

• Amino acids are joined by the formation of a peptide bond through the elimination of water.
• The residue with the free amino group is called the N-terminus or the amino terminus, the residue
with the free carboxylate is the C-terminus or carboxyl terminus
 Nomenclature of Peptides

• Amino acid residues in peptides are named by beginning at the amino terminal end and by
dropping the ine suffix of the amino acid and adding yl.
• The above peptide is called.
serylglycyltyrosylalanylleucine
Or Ser-Gly-Tyr-Ala-Leu
Or SGYAL