Amino Acids (18.1-18.3)

Amino acids have the same basic structure
20 common amino acids combine in different sequences to form thousands of
different proteins
Amino acids differ here
H
All amino acids have
Cg
R
C
H 3N
COO-
General Structure
gamma carbon
O
R C C C C O
beta carbon alpha carbon
Cb
Ca
Carboxylic acid
H
H 3N
R
C
Beta and gamma carbons
COO-
alpha carbon
Ca
amino acid
1
Which of the following are alpha amino acids and which are not?
2
Classification of Amino Acids
Nonpolar
amino acids
H3N CH C O
H3N CH C O
O
H
CH3
glycine
alanine
CH2
CH3
CH2
CH CH3
CH3
CH3
isoleucine
O
H3N CH C O
methionine
HN
phenylalanine
O
O
H3N CH C O
H3N CH C O
O
H3N CH C O
H3N CH C O
CH2
CH2
CH2
CH CH3
C O
CH2
SH
OH
OH
NH 2
C O
cysteine
serine
asparagine
NH2
CH C O
H3N CH C O
CH2
CH2
CH2
C O
C O
O
aspartic acid
(aspartate)
CH2
tyrosine OH
Polar
charged
basic
amino acids
O
H3N CH C O
O
glutamic acid
(glutamate)
H3N CH C O
threonine
glutamine
O
O
O
CH2
O
proline
tryptophan
O
H3N CH C O
leucine
C O
H 2N
CH3
Polar
H3N
charged
acidic
amino acids
O
CH2
S
Polar
uncharged
amino acids
H3N CH C O
CH CH3
CH2
CH2
O
CH CH3
valine
H3N CH C O
CH2
H3N CH C O
H3N CH C O
O
H3N CH C O
O
O
O
O
arginine
O
H3N CH C O
O
CH2
CH2
CH2
CH2
CH2
CH2
NH
CH2
C NH2
NH 3
3 NH
lysine
histidine
NH2
H3N CH C O
CH2
N
Amino Acid Abbreviations
Name
Glycine
Alanine
Valine
Leucine
Isoleucine
Proline
Phenylalanine
Tyrosine
Tryptophan
Cysteine
Methionine
Lysine
Arginine
Histidine
Aspartate
Glutamate
Asparagine
Glutamine
Serine
Threonine
3-letter
Single-letter
abbreviation abbreviation
Gly
Ala
Val
Leu
Ile
Pro
Phe
Tyr
Trp
Cys
Met
Lys
Arg
His
Asp
Glu
Asn
Gln
Ser
Thr
G
A
V
L
I
P
F
Y
W
C
M
K
R
H
D
E
N
Q
S
T
4

Amino acids are weak polyprotic acids (18.4)
both the amino and carboxy
groups are protonated at low
pH. Carboxy loses proton first
and then amino loses at high pH.
H H O
H H O
H N C C O
H N C C O H
H R
H R
lower pH

“many protons”
neutral pH
H O
H N C C O
H R
higher pH
Amino acids are zwitterions (dipolar)
zwitterions have charged residues but are electrically neutral
the amino and carboxy charges cancel each other out at neutral pH so aa wo/
charged side chains are uncharged at neutral pH
H
H 3N
R
C
-
Isoelectric point, pI
pH where amino acid is electrically neutral
depends on the R group also
COO
5
Amino Acid pKa’s
Amino Acid
Alanine
Arginine
Asparagine
Aspartic Acid
Cysteine
Glutamic Acid
Glutamine
Glycine
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Proline
Serine
Threonine
Tryptophan
Tyrosine
Valine
a-carboxylic
a-amino
acid
2.34
9.69
2.17
9.04
2.02
8.80
2.09
9.82
1.71
10.78
2.19
9.67
2.17
9.13
2.34
9.60
1.82
9.17
2.36
9.68
2.36
9.68
2.18
8.95
2.28
9.21
1.83
9.13
1.99
10.60
2.21
9.15
2.63
10.43
2.38
9.39
2.20
9.11
2.32
9.62
Side
chain
12.48
3.86
8.33
4.25
6.00
10.53
10.07
6
Titration of Amino Acids
Amino acids have titration curves like diprotic or triprotic acids
net charge
0
+1
-1
pK2
X
O
H2N CH C O
Net
charge
+1
O
H3N CH C OH
H
X
H
pI
X H3N
O
CH C O
H
Net
charge
-1
Net
charge
0
pK1
7
Alanine
similar to diprotic acid
8
Histidine
similar to triprotic acid
9
Amino Acid Questions. Explain in detail with structures and equations where applicable.
1. Given a peptide with the following amino acid sequence, identify the polar amino
acids, the aromatic amino acids, and the sulfur-containing amino acids.
Val-Met-Ser-Ile-Phe-Arg-Cys-Tyr-Leu
2. Write equations to show the ionic dissociation reactions of the following amino acids:
aspartic acid
valine
3. Draw the predominant ionized forms of the following amino acids at pH 7:
glutamic acid
histidine
arginine
4. Based on the pKa information for amino acids, is there any amino acid that could serve
as a buffer at pH 6? If so, which one(s)?
10
Amino acid questions continued.
5. Sketch a titration curve for the amino acid cysteine; indicate the pKa values for all
titratable groups.
11

Amino acids have handedness (18.5-18.6)
Chirality - an object or molecule that cannot be superimposed
on its mirror image image is chiral
your left and right hands are mirror images of each other.
They are non-superimposable mirror images.
You cannot exactly superimpose your left and right hands.
Molecular handedness
Molecules with carbon are frequently chiral
carbon must have 4 different groups bound to it - called
a chiral carbon or chiral center.
non-superimposable
mirror images - chiral
The presence of one chiral carbon always produces a chiral
molecule
A molecule with more than one chiral carbon may or may not
be chiral overall
superimposable
mirror images - achiral
12
In the type of chiral center we are intersted in, carbon must have 4 different groups attached:
The chiral atom that
makes
the overall molecule
chiral
Examples:
Propane
CH3
H
C
H
CH3
Has 2 sets of
Chloroethane
identical groups
attached (the
H
hydrogens and the
methyl groups)
 achiral
Cl
C
H
Has 2 identical
atoms attached
(the hydrogens)
 achiral
CH3
Amino acids
Groups attached to Ca of amino acids
H
H 3N
1.
2.
3.
4.
COOH
NH3+
R group
NH3+
R
C
NH3+
-
COO
Ca
H
4 different groups attached
in all amino acids except
glycine (the R group is hydrogen)
CH3
CH3
Ca
H
COO-
COO-
Alanine
enantiomers
13
Label the chiral center in the following molecules if one is present.
NH3
OH O
H3C
CH
C
H3C
OH
C
NH3
CH3
Cl
H3C
H2
C CH
H3C
H2
C C
CH3
Cl
H2
C CH3
H3C
CH
H2 H2
C C CH3
Two of the 20 common amino acids have two chiral carbon atoms in their structures.
Identify these amino acids, draw their structures below, and label their chiral centers.
14
Enantiomers - molecules that are non superimposable mirror images of each other
Enantiomers have the same name but are distinguished by a prefix
R vs. S system most commonly used
D vs. L is older nomenclature
only L amino acids are in making proteins (L for “Life”)
Enantiomers have many identical physical properties:
melting and boiling points
same pI
same solubility in water
same density
Enantiomers have some physical and chemical properities that differ
rotate plane polarized light in opposite directions
reactivity with other chiral molecules
**biological activity
**odors and tastes
**activity as drugs
15
Examples of the differing biological activity of enantiomers:
CH3
Chiral
center
CH3
O
O
Chiral center
H2C
C
H
H
CH3
L-Carvone
(in spearmint)
Chiral
center
C
CH2
H3C
mirror
D-Carvone
(in caraway)
Chiral center
(R)-Limonene
(S)-Limonene
(smell of oranges) mirror (smell of lemons)
16
Chiral center
Chiral center
O
O
H
O
H
N
O
N
HN
NH
O
O
O
(R)-Thalidomide
(sedative)
H
mirror
CO2H
CH3
O
(S)-Thalidomide
(fetal abnormalities)
HO2C
H
H3C
H3CO
OCH3
(S)-Naproxen
(anti-inflammatory)
mirror
(R)-Naproxen
(liver toxin)
Must be sold
as 97% S
enantiomer
17