Chapter 3

Amino Acids and

Peptides

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Chapter Outline
(3-1) Amino acids are three-dimensional
(3-2) Structures and properties of amino acids
(3-3) Amino acids can act as both acids and bases
(3-4) The peptide bond
(3-5) Small peptides with physiological activity

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Amino Acids Are Three-Dimensional
• Amino acids - Include an amino
group and a carboxyl group, both
of which are bonded to the -
carbon
• Amino group: —NH2 functional
group
• Carboxyl group: —COOH
functional group that disassociates
to give the carboxylate anion, —
COO–, and a hydrogen ion

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Amino Acids Are Three-Dimensional
(continued)

• -carbon - Bonded to a hydrogen and to the side chain

group, R
• Side chain group: Portion of an amino acid that
determines its identity
• Two stereoisomers of amino acids are designated as
L- and D-amino acids based on similarity to
glyceraldehyde
• Stereoisomers: Molecules that differ from each other
only in their configuration

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Amino Acids Are Three-Dimensional
(continued)

Stereoisomers: Molecules that differ from

each other only in their configuration

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Structure and Properties of Amino Acids
• With the exception of glycine, all amino acids have at
least one chiral center (the -carbon) and are chiral
(stereoisomers)
• Vast majority of -amino acids have the L configuration
at the -carbon
• Proline is usually in the L form
• Side chain carbons in amino acids other than glycine
are designated with Greek symbols, starting at -
carbon (β-, γ-, δ-, ε-, and ω-)
• Amino acids can be referred to by three-letter or one-
letter codes

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Table 3.1 - Names and Abbreviations of
the Common Amino Acids

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Essential Amino Acids must be obtained from the diet

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Nonpolar Amino Acids: 9
• Group of amino acids that has nonpolar side chains
• Glycine, alanine, valine, leucine, isoleucine, proline,
phenylalanine, tryptophan, and methionine
• Alanine, valine, leucine, and isoleucine contain
aliphatic hydrocarbon group
• Proline: aliphatic cyclic structure
• Phenylalanine: hydrocarbon group aromatic
• Tryptophan: side chain contains an indole ring, which
is aromatic
• Methionine, side chain contains a sulfur atom in
addition to aliphatic hydrocarbon groupings

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Figure 3.3 - Structures of the Amino Acids
Commonly Found in Proteins

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Polar-Neutral Amino Acids: 6
• Group of amino acids that has polar side chains that
are electrically neutral at neutral pH
• Serine, threonine, tyrosine, cysteine, glutamine, and
asparagine
• Serine and threonine: polar group is a hydroxyl (—OH)
bonded to aliphatic hydrocarbon groups
• Tyrosine: hydroxyl group (phenol) is bonded to an
aromatic hydrocarbon group
• Cysteine: polar side chain contains a thiol group (—
SH)
• Glutamine and asparagine contain amide groups in
their side chains
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Figure 3.3 - Structures of the Amino Acids
Commonly Found in Proteins (continued 1)

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Acidic Amino Acids: Glutamic Acid and
Aspartic Acid: 2
• Glutamic acid and
aspartic acid:
carboxyl groups
• Carboxyl group can
lose a proton,
forming carboxylate
anions
• Side chains
negatively charged
at neutral pH

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Figure 3.3 - Structures of the Amino Acids
Commonly Found in Proteins (continued 2)

Only R group shown in ball-and-stick models and space-filling models

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Basic Amino Acids: 3
• Histidine, lysine, and arginine have basic side chains
• Side chains are positively charged at or near neutral
pH 7
• Lysine: side-chain amino group is attached to an
aliphatic hydrocarbon chain
• Arginine: side-chain is a guanidino group bonded to an
aliphatic hydrocarbon chain
• Histidine: side-chain is an imidazole group

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Figure 3.3 - Structures of the Amino Acids
Commonly Found in Proteins (continued 3)

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Acidity: –COOH Groups

• Average pKa of an –carboxyl group is 2.19, which

makes it a considerably stronger acid than acetic acid
(pKa 4.76)
• Greater acidity is due to the electron-withdrawing
inductive effect of the –NH3+ group

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Basicity: NH3+ groups
• Compared with a value of 10.76 for a 2°
alkylammonium ion, average value of pKa for an –
NH3+ group is 9.47
• Guanidine group - Side chain of arginine is a
considerably stronger base than an aliphatic amine
• Basicity of the guanidino group is attributed to the
large resonance stabilization of the protonated form
relative to the neutral form
• Imidazole group - Side-chain imidazole group of
histidine is a heterocyclic aromatic amine

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 Histidine

• imidazole side chain can be positively charged or

uncharged at neutral pH
• found at active sites of many enzymes that require a
proton donor or proton acceptor
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The Ionizable (Titratable) Side Chains
Enhance Reactivity and Bonding

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Example 3.1 - Structures and Properties
of Amino Acids
• In the following group, identify the amino acids with
nonpolar side chains and those with basic side
chains:
• Alanine, serine, arginine, lysine, leucine, and
phenylalanine
• pKa of the side-chain imidazole group of histidine is
6.0
• What is the ratio of uncharged to charged side chains
at pH 7.0?

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Example 3.1 - Solution
• Amino acids with nonpolar and basic side chains
• Nonpolar - Alanine, leucine, and phenylalanine
• Basic - Arginine and lysine
• Serine is not in either category because it has a polar
side chain
• Ratio of uncharged to charged side chains at pH 7.0
• Ratio is 10:1 because the pH is one unit higher than
the pKa

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Uncommon Amino Acids
• Derived from the common
amino acids
• Produced through
posttranslational modification
• Parent amino acid is modified
after the protein is synthesized
by an organism
• Hydroxylysine and
hydroxyproline are found only
in a few connective-tissue
proteins, such as collagen
• Thyroxine is found only in the
thyroid gland
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Net Charges of Amino Acids
• In a free amino acid, carboxyl group (negative) and
amino group (positive) are charged at neutral pH
• Amino acids without charged groups on their side
chains exist in neutral solution as zwitterions with no
net charge
• Zwitterions are electrically neutral in solutions

a-carbon
positive charge negative charge

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Figure 3.5 - The Ionization of Amino Acids

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Figure 3.5 - The Ionization of Amino Acids

Histidine
Example of amino acid with ionizable (titratable) side chain

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Titration of Amino Acids
• When an amino acid is
titrated, its titration curve
represents the reaction
of each functional group
with a hydrogen ion
• Titration curve of:
• Alanine is that of a diprotic
acid
• Histidine is that of a
triprotic acid

Next slide

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Figure 3.7 - The Titration Curve of Histidine

Functional groups protonated or not?

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pKa Values of Common Amino Acids
• In free amino
acids, -carboxyl
and -amino
groups are
titratable groups

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Isoelectric pH (pI)
• pH at which a molecule has no net charge (positive
and negative charges are the same)
• Known as isoelectric point
pK a1 + pK a2
pI =
2
• pI for glycine falls midway between the pKa values for
the carboxyl and amino groups
1 +
pI = (pK a  COOH  pK a  NH 3 )
2
1
 (2.34 + 9.60) = 5.97
2
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Example 3.2 - Amino Acid Titrations
• Aspartic acid, alanine, arginine, glutamic acid,
leucine, and lysine
• Which of the these amino acids has a net charge of +2
at low pH?
• Which has a net charge of –2 at high pH?

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Example 3.2 - Solution
• Arginine and lysine have net charges of +2 at low pH
because of their basic side chains
• Aspartic acid and glutamic acid have net charges of −
2 at high pH because of their carboxylic acid side
chains
• Alanine and leucine do not fall into either category
because they do not have titratable side chains

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Peptide Bond
• Amide bond between amino acids in a protein
• Individual amino acids can be linked by forming
covalent bonds
• Bond is formed between α-carboxyl group of one
amino acid and the α-amino group of the next one
• Peptides: Molecules formed by linking two to several
dozen amino acids by amide bonds

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Figure 3.8 - Formation of the Peptide
Bond

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Peptide Bond (continued 1)
• Polypeptide chain
• Backbone of a protein
• Formed by linking amino acids by peptide bonds

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Peptide Bond (continued 2)
• Carbon–nitrogen bond in a peptide bond is usually
written as a single bond, with one pair of electrons
shared between the two atoms
• Single bond can be written as a double bond with a
shift in the position of pair of electrons
• Resonance structures: Structural formulas that differ
from each other only in the position of electrons
• Peptide bond can be represented as a resonance
hybrid of two structures
• Peptide bond has partial double bond character
making it stronger than single bonds
• Rotation around it is restricted

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Figure 3.10 - The Resonance Structures of
the Peptide Bond Lead to a Planar Group

Rotation around peptide

bond is restricted
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Small Peptides with Physiological Activity
• Oxytocin and
vasopressin have:
• Physiological
importance as
hormones (peptide
hormones)
• Cyclic structures

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