Lecture 08
Amino Acids
BCH 101
Basic Biochemistry
Proteins
• Proteins with strikingly different properties and activities are produced by joining a
common set of 20 amino acids in many different combinations and sequences
• From the common building blocks- different organisms can make such widely
diverse products as enzymes, hormones, antibodies, transporters, light-harvesting
complexes in plants, the flagella of bacteria, muscle fibers, feathers, spider webs,
rhinoceros horn, antibiotics, and myriad other substances that have distinct
biological functions
• Enzymes are the most varied and specialized
• Catalysts of almost all cellular reactions, enzymes are one of the keys to
understanding the chemistry of life
• Fundamental chemical properties of amino acids
Amino acids in proteins
1. In every living organism, proteins are constructed from a common set of 20
amino acids. Each amino acid has a side chain with distinctive chemical
properties. Amino acids may be regarded as the alphabet in which the language of
protein structure is written.
2. In proteins, amino acids are joined in characteristic linear sequences
through a common amide linkage, the peptide bond. The amino acid sequence
of a protein constitutes its primary structure, first level within the broader
complexities of protein structure.
α-amino acids
• Proteins are polymers of amino acids
• Each amino acid residue joined to its neighbor by a peptide bond
• Twenty different amino acids are commonly found in proteins
• Asparagine, in 1806; threonine, found in 1938
• All the amino acids have trivial or common names
Structure of amino acids
• They have a carboxyl group and an amino group bonded to the same carbon atom
(the α carbon)
• differ from each other in their side chains, or R groups, which vary in structure,
size, and electric charge, and which influence the solubility of the amino acids in
water
• The common amino acids of proteins have been assigned three-letter abbreviations
and one-letter symbols
• Glycine: Gly: G
• Alanine: Ala: A
• Tyrosine: Tyr: Y
20 common amino acids: classified by R-group property
Nonpolar, aliphatic R Polar, uncharged R Positively charged R Aromatic R
1. Glycine Gly G 1. Serine Ser S 1. Lysine Lys K 1. Phenylalanine Phe F
2. Alanine Ala A 2. Threonine Thr T 2. Arginine Arg R 2. Tyrosine Tyr Y
3. Proline Pro P 3. Cysteine Cys C 3. Histidine His H 3. Tryptophan Trp W
4. Valine Val V 4. Asparagine Asn N Negatively charged R
5. Leucine Leu L 5. Glutamine Gln Q 1. Aspartate Asp D
6. Isoleucine Ile I 2. Glutamate Glu E
7. Methionine Met M
20 common amino acids: classified by R-group property
Nonpolar, aliphatic R
1. Glycine Gly G
2. Alanine Ala A
3. Proline Pro P
4. Valine Val V
5. Leucine Leu L
6. Isoleucine Ile I
7. Methionine Met M
20 common amino acids: classified by R-group property
Polar, uncharged R
1. Serine Ser S
2. Threonine Thr T
3. Cysteine Cys C
4. Asparagine Asn N
5. Glutamine Gln Q
20 common amino acids: classified by R-group property
Positively charged R
1. Lysine Lys K
2. Arginine Arg R
3. Histidine His H
20 common amino acids: classified by R-group property
Negatively charged R
1. Aspartate Asp D
2. Glutamate Glu E
20 common amino acids: classified by R-group property
Aromatic R
1. Phenylalanine Phe F
2. Tyrosine Tyr Y
3. Tryptophan Trp W
Uncommon amino acids
• Most are derivatives of common amino acids, through
post-translational modification
• 4-hydroxyproline, a derivative of Pro: found in
collagen
• γ-carboxyglutamate, derivative of Glu: found in
prothrombin (blood clotting) and other Ca2+ binding
proteins
• Some, not post-translational modification, rather
synthesized from special genetic codes (evolutionary)
• Selenocysteine, derivative of Cys: selenium rather
than the sulfur of cysteine
• Pyrrolysine, derivative of Lys: found in methanogenic
bacteria and archaea, role in methane biosynthesis
Uncommon amino acids
• Some has regulatory roles, their modification allows
for regulation of the protein they are part of.
• Phosphoryl, methyl, acetyl, adenylyl, ADP-ribosyl, or
other groups can be added.
• Phosphorylation is the most common
• Phosphoserine: Phosphorylation of serine through its
OH group.
• Phosphothreonine: Phosphorylation of threonine
through its OH group.
• Phosphotyrosine: Phosphorylation of tyrosine
through its OH group.
Uncommon amino acids
• Some may not even be part of a protein
• Ornithine and Citrulline
• Intermediate metabolite of arginine biosynthesis;
• Key metabolite of Urea cycle (Ornithine cycle)
Amino acids can act as both acids and bases
• Acids: anyone who can donate a proton (H+)
• Bases: anyone who can accept a proton (H+)
• Amino acids can do both, exists as zwitterion (German for “hybrid ion”)
• Amphoteric nature; Amphoteric electrolytes > Ampholytes
• The easier H+ is lost, higher the acidity, lower the pH (pK)
Titration curve of Glycine
• In the first stage of the titration, the —COOH
group of glycine (with its lower pKa) loses its
proton
• midpoint of this stage, equimolar
concentrations of the
proton-donor (+H3N—CH2—COOH) and the
proton-acceptor (+H3N—CH2—COO−) species
are present
• At midpoint, pH of the solution (free proton in
the solution) becomes equal to the pKa of the
deprotonating group
• pH at midpoint is 2.34, therefore the pKa of
—COOH of glycine is 2.34
Titration curve of Glycine
• Intermediate stage:
• Deprotonation of the first group is essentially
complete
• Deprotonation of the second group just started
• Glycine mostly exists as its zwitterionic form
• Net charge zero
• The characteristic pH at which the net electric
charge is zero is called the isoelectric point or
isoelectric pH
• For amino acids that has no ionizable group in
the R group, like Glycine here, the pI is the
arithmetic mean of the pK1 and pK2 which is
5.97.
Titration curve of Glycine
• In the second stage of the titration, proton is
removed from the —NH3+ group (higher pKa)
• The pH at the midpoint of this stage is 9.60
• pKa for the —NH3+ group is therefore 9.60
• The titration is essentially complete at a pH of
about 12, at which point the predominant form
of glycine is H2N—CH2—COO−.
• All removable protons are removed
Information from the titration curve of an Amino Acid
1. pKa for the two ionizing groups are obtained; “stabilization of charge”
2. Two buffering zones (at least) are there for one amino acid
3. Relationship between pH and net charge of an amino acid: pI
Stabilization of charge
Titration of charged R-group
containing amino acids
• Three stages of deprotonation
• Stabilization of charges apply here to dictate
the sequence of deprotonation
• Approximate arithmetic mean of the stages
before and after neutral ionic state
determine the pI
Formation of a peptide bond
Peptide bond is directional
Peptide bond is planer and rigid
Cα—C—N—Cα
• Three bonds separate two
successive peptide bonds
• Peptide bond has a partial
double-bond nature, hence
cannot rotate
• Cα—C and N—Cα bonds are single
bond and free to rotate
• N—Cα rotation angle is defined as
the ϕ angle
• Cα—C rotation angle is defined as
the ψ angle
