Reginald H. Garrett
Charles M. Grisham
www.cengage.com/chemistry/garrett
Chapter 4
Amino Acids
Reginald Garrett & Charles Grisham • University of Virginia
Outline
• What are the structures and properties of
amino acids?
• What are the acid-base properties of amino
acids?
• What reactions do amino acids undergo?
• What are the optical and stereochemical
properties of amino acids?
• What are the spectroscopic properties of
amino acids?
• How are amino acid mixtures separated and
analyzed?
• What is the fundamental structural pattern in
proteins?
4.1 What Are the Structures and
Properties of Amino Acids?
• Amino acids contain a central tetrahedral
carbon atom
• There are 20 common amino acids (you
need to know all of them)
• Amino acids can join via peptide bonds
• Several amino acids occur only rarely in
proteins
• Some amino acids are not found in
proteins
4.1 What Are the Structures and
Properties of Amino Acids?
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.
4.1 What Are the Structures and
Properties of Amino Acids?
Two amino acids
can react with
loss of a water
molecule to form
a covalent bond.
The bond joining
the two amino
acids is called a
peptide bond.
The 20 Common Amino Acids
You should know names, structures,3-letter and
1-letter codes
•
•
•
•
Non-polar amino acids
Polar, uncharged amino acids
Acidic amino acids
Basic amino acids
The 20 Common Amino Acids
Some of the nonpolar (hydrophobic) amino acids.
The 20 Common Amino Acids
More of the nonpolar (hydrophobic) amino acids.
The 20 Common Amino Acids
Some of the polar, uncharged amino acids.
The 20 Common Amino Acids
More of the polar, uncharged amino acids.
The 20 Common Amino Acids
The acidic amino acids.
The 20 Common Amino Acids
The basic amino acids.
Several Amino Acids Occur Rarely in Proteins
We'll see some of these in later chapters
•
•
•
•
•
•
Selenocysteine in many organisms
Pyrrolysine in several archaeal species
Hydroxylysine, hydroxyproline - collagen
Carboxyglutamate - blood-clotting proteins
Pyroglutamate – in bacteriorhodopsin
GABA, epinephrine, histamine, serotonin act as
neurotransmitters and hormones
• Phosphorylated amino acids – a signaling
device
Several Amino Acids Occur Rarely in Proteins
Several Amino Acids Occur Rarely in Proteins
Several Amino Acids Occur Rarely in Proteins
4.2 What Are Acid-Base Properties of
Amino Acids?
• Amino Acids are Weak Polyprotic Acids
• The degree of dissociation depends on the pH
of the medium
H2A+ + H2O ↔ HA0 + H3O+
0

[HA ][H3O ]
Ka1 

[H2 A ]
4.2 What Are Acid-Base Properties of
Amino Acids?
The second dissociation (the amino group in the case
of glycine):
HA0 + H2O ↔ A− + H3O+

Ka 2

[A ][H3O ]

0
[HA ]
4.2 What Are Acid-Base Properties of
Amino Acids?
The ionic forms of the amino acids, shown without
consideration of any ionizations on the side chain.
pKa Values of the Amino Acids
You should know these numbers and know
what they mean
• Alpha carboxyl group: pKa = 2
• Alpha amino group: pKa = 9
• These numbers are approximate, but
entirely suitable for our purposes.
4.2 What Are Acid-Base Properties of
Amino Acids?
4.2 What Are Acid-Base Properties of
Amino Acids?
Titrations of polyprotic amino acids
Titration of glutamic acid
A Sample Calculation
What is the pH of a glutamic acid solution
if the alpha carboxyl is 1/4 dissociated?
[1]
pH = 2 + log10
[3]
• pH = 2 + (−0.477)
• pH = 1.523
•
Note that, when the group is ¼ dissociated, ¼ is
dissociated and ¾ are not; thus the ratio in the
log term is ¼ over ¾ or ⅓.
Reactions of Amino Acids
• Carboxyl groups form amides & esters
• Amino groups form Schiff bases and
amides
• Edman reagent (phenylisothiocyanate)
reacts with the α-amino group of an amino
acid or peptide to produce a
phenylthiohydantoin (PTH) derivative.
• 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
Reactions of Amino Acids
Cysteine residues react with each other to form disulfides. This
reaction is an oxidation-reduction reaction.
Green Fluorescent Protein
A jellyfish (Aequorea victoria)
native to the northwest
Pacific Ocean contains a
green fluorescent protein.
GFP is a naturally fluorescent
protein. Genetic engineering
techniques can be used to
“tag” virtually any protein,
structure, or organelle in a
cell with GFP. The
luminescent chromophore of
GFP lies in the center of a βbarrel protein structure.
Green Fluorescent Protein
The prosthetic group of GFP is an oxidative product of the
sequence –FSYGVQ-.
Stereochemistry of Amino Acids
• All but glycine are chiral
• L-amino acids predominate in nature
• D,L-nomenclature is based on D- and Lglyceraldehyde
• R,S-nomenclature system is superior,
since amino acids like isoleucine and
threonine (with two chiral centers) can be
named unambiguously
Stereochemistry of Amino Acids
Spectroscopic Properties
• All amino acids absorb at infrared
wavelengths
• Only Phe, Tyr, and Trp absorb UV
• Absorbance at 280 nm is a good
diagnostic test 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
Spectroscopic Properties
Figure 4.10 The
UV spectra of the
aromatic amino
acids at pH 6.
Spectroscopic Properties
Proton NMR spectra of several amino acids.
4.7 What is the Fundamental Structural
Pattern in Proteins?
• Proteins are unbranched polymers of amino acids
• Amino acids join head-to-tail through formation of
covalent peptide bonds
• Peptide bond formation results in release of water
• The peptide backbone of a protein consists of the
repeated sequence –N-Cα-Co• “N” is the amide nitrogen of the amino acid
• “Cα” is the alpha-C of the amino acid
• “Co” is the carbonyl carbon of the amino acid
4.7 What is the Fundamental Structural
Pattern in Proteins?
Peptide formation is the creation of an amide bond
between the carboxyl group of one amino acid and the
amino group of another amino acid.
The Peptide Bond
•
•
•
•
is usually found in the trans conformation
has partial (40%) double bond character
N partially positive; O partially negative
has a length of about 0.133 nm - shorter than a
typical single bond but longer than a double
bond
• Due to the double-bond character of the
peptide bond, the six atoms of the peptide bond
group define a plane – the amide plane
The Peptide Bond
The trans conformation of the peptide bond.
4.7 What is the Fundamental Structural
Pattern in Proteins?
The peptide bond has partial double bond character. One of
the postulated resonance forms is shown here.
4.7 What is the Fundamental Structural
Pattern in Proteins?
Figure 4.16 (b) The peptide bond has partial double
bond character. One of the postulated resonance
forms is shown here.
4.7 What is the Fundamental Structural
Pattern in Proteins?
Figure 4.16 (c) The peptide bond is best described as a
resonance hybrid of the forms shown on the two previous
slides.
4.7 What is the Fundamental Structural
Pattern in Proteins?
The coplanar relationship of the atoms in the amide group
is highlighted here by an imaginary shaded plane lying
between adjacent α-carbons.
“Peptides”
•
•
•
•
•
•
Short polymers of amino acids
Each unit is called a residue
2 residues - dipeptide
3 residues - tripeptide
12-20 residues - oligopeptide
many - polypeptide
“Protein”
One or more polypeptide chains
•
•
•
•
•
•
One polypeptide chain - a monomeric protein
More than one - multimeric protein
Homomultimer - one kind of chain
Heteromultimer - two or more different chains
Hemoglobin, for example, is a heterotetramer
It has two alpha chains and two beta chains
Proteins - Large and Small
• Insulin - A chain of 21 residues, B chain of 30
residues -total mol. wt. of 5,733
• Glutamine synthetase - 12 subunits of 468
residues each - total mol. wt. of 600,000
• aConnectin (a muscle protein) - MW 2.8 million
• bConnectin - MW of 2.1 million, with a length of
1000 nm - it can stretch to 3000 nm
Proteins - Large and Small
Proteins - Large and Small
From Table 4.2 Size of protein molecules.
Molecular weights:
Insulin, 5,733
Cytochrome c, 12,500
Ribonuclease, 12,640
Lysozyme, 13,930
Myoglobin, 16,980
Proteins - Large and Small
From: Table 4.2 Size of Protein Molecules
Molecular weights: Hemoglobin, 64,500;
Immunoglobulin, 149,900;
Glutamine synthetase, 600,000.
The Sequence of Amino Acids in a Protein
•
•
•
•
Is a unique characteristic of every protein
Is encoded by the nucleotide sequence of DNA
Is thus a form of genetic information
Is read from the amino terminus to the
carboxyl terminus
• Questions: 1-9, 13-16, 18