Amino Acids
Proteins are composed of 20 common amino acids
Each amino acid contains:
(1) Carboxylate group
(2) Amino group
(3) Side chain unique to each amino acid
Drawn at very acidic pH (pH=1)
Amino Acids (pg 29 v7)
(1) Hydrophobic (non polar)
(2) polar uncharged
(3) positively charged
(4) negatively charged
(5) aromatic
Stereochemistry of amino acids
19 of the 20 common amino acids have a chiral a-carbon atom
(Gly does not)
Threonine and isoleucine have 2 chiral carbons each
Mirror image pairs of amino acids are designated L (levo) and D
(dextro)
Proteins are assembled from L-amino acids
(a few D-amino acids occur in nature)
Two amino acids (Thr, Ile) also have a chiral C
atoms in their sidechains (R).
Which carbon’s are chiral in Isoleucine?
*
*
4
=R
Amino Acid Problems
1. Which statement is NOT correct about classification of amino acids?
A) alanine and valine are neutral, nonpolar amino acids
B) lysine and arginine are basic amino acids
C) tryptophan and phenylalanine are aromatic amino acids
D) aspartic acid and asparagine are acidic amino acids
E) alanine and isoleucine are aliphatic amino acids
: :
2. Which of the following amino acids is the LEAST water soluble at
pH 7.0? WHY?
A) tryptophan
B) glutamic acid
:
C) tyrosine
D) histidine
E) lysine
Amino Acid Problems
1. Which statement is NOT correct about classification of amino acids?
A) alanine and valine are neutral, nonpolar amino acids
B) lysine and arginine are basic amino acids
C) tryptophan and phenylalanine are aromatic amino acids
D) aspartic acid and asparagine are acidic amino acids
E) alanine and isoleucine are aliphatic amino acids
: :
2. Which of the following amino acids is the LEAST water soluble at
pH 7.0? WHY?
A) tryptophan
B) glutamic acid
:
C) tyrosine
D) histidine
E) lysine
Amino Acid Problems
3. Which of the following groups in a protein CANNOT form
Hydrogen-bonds with an Arginine sidechain at pH 7? Why?
A) Aspartate
B) Glutamate
C) Terminal carboxylate
D) Mainchain (backbone) carbonyl
E) Lysine
4. Which of the following is NOT a biological role of amino acids?
A) primary energy carrier molecules within cells
B) components of proteins
C) components of peptide hormones
D) biological buffers
E) all of the other choices are biological uses of amino acids
Amino Acid Problems
3. Which of the following groups in a protein CANNOT form
Hydrogen-bonds with an Arginine sidechain at pH 7? Why?
A) Aspartate
B) Glutamate
C) Terminal carboxylate
D) Mainchain (backbone) carbonyl
E) Lysine also a donor
4. Which of the following is NOT a biological role of amino acids?
A) primary energy carrier molecules within cells ATP
B) components of proteins
C) components of peptide hormones
D) biological buffers
E) all of the other choices are biological uses of amino acids
Ionization state of an Amino Acid Depends on pH
Are the amino and carboxy termini the only ionizable groups in
amino acids?
No pKaR!!!
R
Ionization state of an Amino Acid Depends on pH
Predominant form
at pH = 1
+1
Predominant form
at pH = 7
0
Predominant form
at pH = 11
-1
Titration of the Amino Acid Alanine
H O
What is the Net
charge of each
species?
H2N C C OH
CH3
1 all A
A=
fully deprotonated
2 [B] = [A]
3 all B
B=
neutral species
4 [C] = [B]
C=
5 all C
fully protonated
3) At what pH is the net charge zero species at a maximum?
Isoelectric Point (pI) of an Amino Acid
• pI is the pH at which an amino acid is electrically neutral
• pI is the pH at which the average net charge of amino acid is zero
For an amino acid without an ionizable sidechain (2 pKa’s), the
pI occurs half-way between the two acid dissociation constants
(pKa) values:
pI = (pK1 + pK2) / 2
pK1 = 2.4
pK2 = 9.8
pK1 = 2.4
pK2 = 9.8
pKR = sidechain if ionizable
http://higheredbcs.wiley.com/legacy/college/voet/0471214957/animated_figures/ch04/f4-8.html
Effect of Sidechain Functional Group on Amino Acid’s pI
Several of the amino acids have ionizable sidechains, (3 pKa’s)
Glutamic acid
The pI calculation is more complicated by the presence of three (3)
ionizable groups in one amino acid (triprotic acid)
 First assign pKas given to the correct functional groups:
O
9.7
+H3N
CH C
CH2
CH2
4.3
C
OH
O
O-
2.2
Acid-Base Properties of Glutamic Acid
O
+H3N
At what pH range is the charge of Glu
closest to zero?
Or at what pH range will Glu be present
predominantly in the form shown to the right?
CH C
CH2
CH2
C
OH
O
O-
Isoelectric Point (pI) of Glutamic Acid
Net Charge?
+1
0
-1
-2
Glu: the pI is given by the
average of the pKa values of
the two COOH groups which
ionize on either side of the
neutral species:
pI = (pK1+pKR)/2
For amino acids with three
ionizable groups, either polar
charged ones
His, Lys, Arg, Glu, and Asp) or
Cys, Tyr,
pI reflects the chemical nature
of the sidechain R group.
pI represents the collective “pKa” of the entire molecule
Nonpolar amino acids: pI is near 7 (neutral pH)
pI = (pKN + pKC) / 2
2) Acidic amino acids (RCOOH groups in sidechain):
cellular pH ~7 the sidechain carboxy group is
deprotonated and can act as a BASE
pI = (pKC + pKR) / 2
3) Basic amino acids (RNH3+ groups in sidechain):
cellular pH ~7 the sidechain amino groups are
protonated and can act as a ACID
pI = (pKN + pKR) / 2
Forming Biological Molecules
dehydration synthesis: formation of large molecules by
the removal of water
-monomers are joined to form polymers
Breaking Biological Molecules
hydrolysis: breakdown of large molecules by the
addition of water
-polymers are broken down to monomers
Peptides!
H3N+
Lue-enkephalin: pentapeptide endorphin bind to opioid receptor;
regulate pain
Tyr-Gly-Gly-Phe-Leu
YGGFL
Properties of polypeptides in solution
Water molecules interact with
polar side chains to form a
hydration layer containing
0.3g water per gram of protein,
about two waters for every amino
acid residue.
This bound hydration layer has
different properties to bulk water.
The density is 10% higher and it
has a 15% greater heat capacity
suggesting much reduced
molecular motion.