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Associations of amphipathic
molecules in aqueous solutions.
Ionic Mobilities in H2O at 25°C.
Mean lifetime of a
hydronium ion is 10-12 s
This makes proton transfer reactions (acid base
reactions) among the fastest in aqueous solutions.
Acid Base Chemistry
Conjugate acid
Conjugate base
HA + H2O
K=
H3O+ + A[H3O+][A-]
[HA][H2O]
+][A-]
[H
Ka = K[H2O] =
[HA]
[H2O] = 55.5M
[H3O+] = [H+]
K = dissociation constant is a measure of the
strength of an acid
Water as an acid
Conjugate acid
Conjugate base
H2O
K=
H+ + OH[H+][OH-]
[H2O]
[H2O] = 55.5M
Kw = K[H2O] = [H+][OH-]
Pure water contains equimolar hydroxide ions
and protons
At 25ºC Kw = 10-14 M2
[H+] = [OH-] = 10-7 M
Henderson Hasselbach and pH
pH = -log[H+]
[H+] = Ka([HA]/A-])
pH = -log Ka + log ([A-]/[HA])
pH = pKa + log ([A-]/[HA])
Titration curve of a 1L solution of 1M H3PO4.
Thermodynamics
First Law
Energy is conserved
∆U = Ufinal - Uinitial = q - w
q = heat absorbed
w = work done
∆U = 0 for any process that returns to its initial state
Exothermic processes release heat
Endothermic processes gain heat
Enthalpy is defined as:
H = U + PV
∆H = ∆U + P∆V
P = pressure (constant)
∆V = volume (insignificant)
∆H = ∆U = q - w
∆H = q
w often is
zero in
biological
systems
q = heat transferred to/from the surroundings
Thermodynamics
Second Law
Entropy increases
∆Suniverse > 0
N molecules of gas
2N equally
probable
ways of
distributing
them
Two bulbs of equal volumes connected
by a stopcock.
N!
WL =
L!(N-L)!
WL = number of different ways of
placing L of the N molecules in the
left bulb
Probability = WL/2N
For any N the most probable state is
L = N/2 (half the gas in the left bulb)
If N = 1023 the probability that the # of molecules in
the left and right bulbs differ by 1 molecule is 10
billion in 10-434
WL = number of different ways of
placing L of the N molecules in the
left bulb
N!
WL =
L!(N-L)!
9 positions, 4 identical balls
Page 54
W = 9•8•7•6•5•4•3•2•1 = 126
(4•3•2•1)(5•4•3•2•1)
Only 4 out of 126 possible
arrangements have 4 balls
touching each other
N!
WL =
L!(N-L)!
W is approximately 107x1022 if
the previous experiment uses a
mole of real gas
To make this more manageable entropy was “invented”
S = kB ln W
In a system where energy does not change a
spontaneous process has ∆S > 0
This does not mean that order cannot exist
In a localized system.
It means that order can only exist at the
expense of surrounding systems.
Biology gains order by disordering the
nutrients that it consumes.
∆Ssystem + ∆Ssurroundings = ∆Suniverse > 0
Free Energy
G = H - TS
∆G = ∆H - T∆S
∆G ≤ 0 for a spontaneous process
Exergonic
Endergonic
∆G < 0
∆G > 0
Spontaneous
Must input energy
Variation of Reaction Spontaneity (Sign of
∆G) with the signs of ∆H and ∆S.
How do we drive endergonic processes?
Greek lettering scheme used to identify the
atoms in the glutamyl and lysyl R groups.
An a-amino acid
COOH
C
a
COO-
HS
NH3+
H
C
a
NH3+
H
HS
C a
HS
+H3N
O-
a
C
O
Fischer Projection
Preferred representation
Glycine - The Simplest a-Amino Acid
H
C
CH3
a
NH3+
H
COOC
a
+H3N
CH3
b
NH3+
(X)
CH3
Ca
H
L-a-alanine or
(-)- a -alanine
Alanine
COO-
NH3+
-OOC
O-
H(Z)
C
O
(W)
Ca
CH3
(Y)
(S)-a-alanine
S = counterclockwise
g1
COOH
C
a
b
CH3
a-valine
L-(-)-a-valine
S-a-valine
Valine
CH
g2
CH3
NH3+
COOH
a
C
NH3+
CH3
(X)
NH3+
-OOC
CH
H3C
CH3
H
CH
Ca
O-
Ca
+H3N
H(Z)
CH3
C
O
CH
H3C
(Y)
CH3
(W)
d1
CH3
COOH
C
b
CH2
a
CH g
COOH
C
Leucine
CH3
d2
NH3+
a
a -leucine
L-a-leucine
(-) -a-leucine
S-a-leucine
CH3
CH2
CH
(X)
CH3
NH3+
NH3+
-OOC
H3C
CH
H
+H3N
Ca
CH2
C a
H(Z)
CH3
(Y)
O-
C
O
CH2
CH
H3C
CH3
(W)
Isoleucine
2 chiral centers
COO- CH3 2
g
H
C
a
b
C
CH2
g1
d1
CH3
(2S,3S)-isoleucine
NH3+ H
CH2CH3
H3C
-OOC
H
CH3
a
C
+H3N
C
H
H
C
Ca
CH2CH3
+H3N
H
O-
C
O
Isoleucine
2 chiral centers
(2S,3S)-isoleucine
(X)
NH3+
-OOC
(W)
(W)
Ca
H(Z)
(Y)
H
C
H3CH2C
CH3
Ca
H(Z)
Cb
CH3
(X) CH2CH3
Both centers are S
(Y)
Methionine is non-polar but S-atom is
a-methionine
reactive
L-methionine
(-)-a-methionine
S-methionine
COOH
C
a
b
CH2
g
CH2
d
S
e
CH3
NH3+
-OOC
H
C
+H3N
a
CH2
CH2
S
CH3
Methionine is non-polar but S-atom is
a-methionine
reactive
L-methionine
(-)-a-methionine
S-methionine
H
CH2
Ca
+H3N
CH2
S
CH3
OC
(X)
NH3+
-OOC
(W)
O
H(Z)
Ca
(Y) CH2CH2SCH3
a-proline
L-proline
(-)-a-proline
S-proline
Proline is a cyclic imino acid
-OOC
COOH
C
H
+
C
CH2
N
a
H2
CH2
HN
2
H2
C
C
H2
b
a
g
e
CH2
d
CH2
+
CH2
H
H2C
C
N+
H2
(X)
CH2
a
+
-OOC
(W)
OC
H
N2
H(Z)
Ca
CH2
CH2
O
(Y)H2C
a-phenylalanine
L-phenylalanine
(-)-a-phenylalanine
S-phenylalanine
COOH
a
C
NH3+
Large non-polar
aromatic
d1
-OOC
CH2
a
H
C
+H3N
b
g
CH2
e1
z1
d2
e2
Large and non-polar
a-phenylalanine
L-phenylalanine
(-)-a-phenylalanine
S-phenylalanine
(X)
NH3+
-OOC
(W)
H(Z)
Ca
H
CH2
C
+H3N
a
C
O
(Y) CH2
O-
a-tryptophan
L-tryptophan
(-)-a-tryptophan
S-tryptophan
Large and non-polar
COOH
C
a
NH3+
CH2
z3
e3
h2
NH
-OOC
a
H
C
+H3N
b
g
CH2
d1
d2
e2
N
e1
H
z2
a-tryptophan
L-tryptophan
(-)-a-tryptophan
S-tryptophan
Large and non-polar
H
N
(X)
NH3+
-OOC
(W)
H(Z)
H
C
+H3N
Ca
CH2
a
O-
(Y) CH2
C
O
HN
a-tyrosine
L-tyrosine
(-)-a-tyrosine
S-tyrosine
Uncharged Polar Amino
Acids
COOH
C
a
CH2
OH
NH3+
d1
-OOC
H
C
a
+
NH3
b
CH2
g
e1
z1
OH
h
d2
e2
a-tyrosine
L-tyrosine
(-)-a-tyrosine
S-tyrosine
Uncharged Polar Amino
Acids
OH
NH3+
-OOC
(X)
(W)
H(Z)
Ca
(Y)
CH2
H
CH2
Ca
+H3N
OC
O
OH
a-serine
L-serine
(-)-a-serine
S-serine
Uncharged Polar Amino Acids
COOH
C
-OOC
CH2
OH
NH3+
a
H
a
C
b
g
CH2
OH
(X)
NH3+
-OOC
(W)
+
NH3
OH
H
Ca
CH2
C
+H3N
H(Z)
a
OC
O
(Y) CH2
OH
Uncharged Polar Amino Acids cysteine is often charged
a-cysteine
L-cysteine
(-)-a-cysteine
R-cysteine
-OOC
NH3+
-OOC
H
C
a
b
g
CH2
SH
(W)
(Y)
H(Z)
Ca
+
NH3
SH
COOH
C
a
NH3+
H
CH2
CH2
+H3N
OC
O
CH2
SH
SH
C a
(X)
a-asparagine
L-asparagine
(-)-a-asparagine
S-asparagine
Uncharged Polar Amino Acids
O
C
H
O
b
CH2
a
H
C
NH2
d2
NH3
+H3N
a
O-
C
O
C g
+
CH2
C
d1
-OOC
NH2
NH3+
-OOC
(X)
(W)
H(Z)
COOH
a
C
NH3+
Ca
O
(Y)
CH2
C
CH2
NH2
C
O
NH2
a-glutamine
L-glutamine
(-)-a-glutamine
S-glutamine
Uncharged Polar Amino Acids
O
C
H
H2C
e1
-OOC
a
C
b
g
CH2 CH2
O
d
H
NH2
e2
NH3
H
C
a
C
O-
NH3+
-OOC
(X)
(W)
H(Z)
O
Ca
COO-
a
CH2
C
C
+H3N
+
NH2
O
(Y)
CH2
CH2
CH2
C
CH2
NH3+
NH2
C
O
NH2
-OOC
H
a
Threonine has 2 chiral
centers
H
(2S,3R)-threonine
b
C
C
CH3
g2
+H3N
H
H
OH
H
g1
-OOC
a
C
NH3+
+H3N
OH
C
Ca
H
C
CH3
OH
OC
CH3
O
Threonine has 2 chiral
centers
(2S,3R)-threonine
NH3+
-OOC
(X)
(W)
Ca
(X)
CH3
(Y)
H(Z)
Ca
H(Z)
(Y)
HO
C
CH3
H
Cb
(W)
OH
a-arginine
L-arginine
(-)-a-arginine
S-arginine
Charged amino acids
H
h2
-OOC
H
C
a
b
g
CH2
CH2
d
CH2
z
e
NH
NH2
C
+H3N
C
NH3
h1
-OOC
-OOC
NH3+
CH2
CH2
CH2
C
(X)
NH3+
H(Z)
NH
H2N
O-
NH2+
a
C
a
C
CH2
O
NH2+
+
H
CH2
NH2+
NH
CH2
(W)
NH2+
Ca
NH2
(Y)
H2
C
H2C
C
H2
C
N
H
NH2
a-lysine
L-lysine
(-)-a-lysine
S-lysine
-OOC
H
C
a
b
CH2
g
d
CH2 CH2
Charged amino acids
e
CH2
H
z
NH3+
+
Ca
a
OC
-OOC
C
NH3+
CH2
CH2
+H3N
NH3
H
CH2
CH2
O
CH2
CH2
CH2
CH2
NH3+
-OOC
(X)
NH3+
NH3+
H(Z)
(W)
Ca
(Y)
H2C
NH3+
CH2
CH2
CH2
a-histidine
L-histidine
(-)-a-histidine
S-histidine
-OOC
HN
H d1
N
b
a
H
Charged amino acids
C
e1
H
g
CH2
N
+
NH3
d2
e2
+
H
H
N
H
C
a
CH2
C
a
O-
C
+H3N
-OOC
-OOC
NH+
O
(X)
NH3+
H(Z)
(W)
Ca
CH2
NH+
(Y)
H2C
H
N
NH3+
NH+
a-glutamate
L-glutamate
(-)-a-glutamate
S-glutamate
Charged amino acids
O
H 2C
e1
-OOC
H
C
b
g
CH2
CH2
C
a
O
O-
C
d
O
NH3+
-OOC
(X)
(W)
e2
COO-
NH3+
C
O-
NH3
Ca
CH2
+H3N
+
H
H
O
a
H(Z)
Ca
(Y)
CH2
CH2
CH2
O-
C
C
CH2
OC
O
O-
a-aspartate
L-aspartate
(-)-a-aspartate
S-aspartate
d1
-OOC
O
H
C
CH2
O
C
g
NH3
CH2
C
O-
+
a
O
-OOC
O
C
NH3+
CH2
NH3+
(X)
(W)
H(Z)
a
H
O-
C
+H3N
d2
COO-
O-
C
H
b
a
Charged amino acids
C
Ca
(Y)
CH2
O-
C
O
O-
Alanine
Cysteine
Glycine
Histidine
Isoleucine
Leucine
Methionine
Proline
Serine
Threonine
Valine
Ala
Cys
Gly
His
Ile
Leu
Met
Pro
Ser
Thr
Val
A
C
G
H
I
L
M
P
S
T
V
Arginine
Asparagine
Aspartate
Glutamate
Glutamine
Lysine
Phenylalanine
Tryptophan
Tyrosine
Arg
Asn
Asp
Glu
Gln
Lys
Phe
Trp
Tyr
R
N
D
E
Q
K
F
W
Y
Non-standard encoded amino acids
-OOC
H
C
a
CH2
Selenocysteine
Sec, U
SeH
+
NH3
-OOC
O
H
C
a
CH2 CH2
CH2
CH2
H
N
CH3
NH3+
N
Pyrrolysine
Pyl, O
Amino acids bear structural similarity to each other
Asparate
Glutamate
d1
-OOC
H
C
b
CH2
C
g
H
O-
+
NH3
d2
Asparagine
-OOC
b
CH2
C
+
NH3
C
O
a
b
g
CH2
CH2
NH3+
d
e2
Glutamine
e1
O
-OOC
C g
NH2
d2
C
O-
d1
O
a
H
-OOC
O
a
e1
H
a
C
b
g
CH2 CH2
+
NH3
d
C
NH2
e2
Amino acids bear structural similarity to each other
Cysteine
Selenocysteine
-OOC
-OOC
H
C
a
b
g
CH2
SH
a
H
C
CH2
SeH
+
NH3
+
NH3
Threonine
Serine
-OOC
H
a
H
-OOC
b
C
C
CH3
g2
+H3N
OH
g1
a
H
C
+
NH3
b
g
CH2
OH
Amino acids bear structural similarity to each other
Tyrosine
d1
-OOC
H
C
b
a
CH2
+
NH3
g
e1
z1
OH
h
d2
e2
Phenylalanine
d1
-OOC
a
H
C
+H3N
b
g
CH2
e1
z1
d2
e2
Amino acids bear structural similarity to each other
H
H
Histidine
H
N
N
CH2
CH2
CH2
H
CH2
N+
Asparagine O
H
H
Histidine
H
Histidine
N
N+
N
Glutamine
HH
O
HH
H
H
CH2
+
N
N
Arginine
N
CH2
H Histidine
N
NH2+
N
CH2
CH2
Arginine
+H N
2 +
N
H
H
Amino acids bear structural similarity to each other
Histidine
H
N
CH2
CH2
Tryptophan
N+
N
HH
Amino acids bear structural similarity to each other
OH
Phenylalanine
Tyrosine
H3C
CH
2 2
CH
CH3
CHCH
2 2
Phenylalanine
Leucine
N
• Glutamate, glycine
N
H2N
– neurotransmitters
• D-serine
N
H
N
– neurotransmitter
• S-adenosylmethionine
– methyl transfer
H
OH
H
OH
O
-OOC
H
C
NH3+
H
CH2 CH2
S
CH3
Page 77
Non-peptide amino acids
Titration curve of glycine.
These values are the pKa’s of the free amino acids in
aqueous solution. As we shall see later an aqueous
solution may not represent reality
O
C
-O
H
H
N
CH2
O-
C
+H3N
N
C
O
H
O
CH2
These values are the pKa’s of the free amino acids in
aqueous solution. As we shall see later an aqueous
solution may not represent reality
Hydrophobic pocket
O
C
OH