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3
Biochemistry
by Mary K. Campbell
& Shawn O. Farrell 8th. Ed.
2016
3-1
3
Amino Acids
&
Peptides
3-2
3 Learning Objectives
1. What are amino acids, and what is their threedimensional structure?
2. What are the structures and properties of the
individual amino acids?
3. Do amino acids have specific acid–base
properties?
4. What is the peptide bond?
5. Are small peptides physiologically active?
3-3
3 Amino Acids
Amino acid: a compound that contains both
an amino group and a carboxyl group
composed from -carbon to which Hydrogen
atom, R-group, -amino group and -carboxyl
group are attached.
The -amino acid: the amino group is attached to
the -carbon
although amino acids are commonly written in
the unionized form, they are more properly
written in the zwitterion form:
O
R- CH-COH
O
R- CH-CO -
N H2
N H3 +
unionized
form
zwitterion
Zwitterion: a molecule with both
–ve and +ve charges
3-4
3 Chirality of Amino Acids
With the exception of glycine, all protein-derived
amino acids are chiral and have at least one
asymmetric (chiral) carbon
(normally the α-carbon)
-
COO
‫׀‬
H - C - NH3+
‫׀‬
R
α- carbon
3-5
3
The three-dimensional (3D) shape of an AA can be
represented in different ways:
COO-
COO-
COO
COO
H
N H3 + + H 3 N
H
+
+
H
N
H
H
3 CH H 3 N
CH
3
R
CH3L-Alanine
(Fischer
projections)
D-Alanine
D-Alanine
3
CH3
L-Alanine
3-6
3 Chirality of Amino Acids
Chiral amino acids have two stereoisomers
(=optical isomers=different spatial arrangement
of atoms around chiral carbon)
The mirror-image stereoisomers are called
enantiomers.
Two forms of enantiomers: L- & D- forms.
the majority of amino acids have the L-configuration at
the α-carbon
COO-
H
N H3 +
COO-
+
H 3N
CH 3
D-Alanine
H
CH3
L-Alanine
(Fischer projections)
3-7
3
Comparison of the stereochemistry (3D structure)
of alanine and glyceraldehyde (Fischer projection
formulas)
the naturally
occurring form
COOH
N H3 +
COO+
H 3N
CH3
D-Alanine
CH3
L-Alanine
CHO
the naturally
occurring form
H
OH
CH2 OH
D-Glyceraldehyde
H
CHO
HO
H
CH 2 OH
L-Glyceraldehyde
3-8
3
** In most cases, D-amino acids are
toxic.They occur in nature in
antibiotics and bacterial cell walls.
3-9
3 20 Protein-Derived a.a.
Nonpolar side chains (predominant form at pH 7.0)
glycine (gly)
Halanine (ala)
CH3 -
phenylalanine (phe)
tryptophan (trp)
valine (val)
( CH3 ) 2CH
N
H
leucine (leu)
( C H 3 ) 2 C H CH 2 -
isoleucine (ile)
CH3 CH2 CH( CH3 ) methionine (met)
proline (Pro)
+
N
H
H
C H 3 SC H 2 C H 2 3-10
3
Polar side chains (predominant form at pH 7.0)
asparagine (asn)
O
H2 N CC H
serine (ser)
2
-
glutamine (gln)
threonine (thr)
O
H2 N CC H
H O C H2 -
O H
2
C H2 -
C H3 C H -
3-11
3
3-12
3
Basic side chains (predominant form at pH 7.0)
arginine (arg, R)
NH2 +
H2 NCNHCH2 CH2 CH2 lysine (lys, K)
histidine (his, H)
N
N
CH2 -
H
+
H3 NCH 2 CH 2 CH 2 CH 2 -
a.a. may be classified as aliphatic or aromatic:
•Aliphatic a.a have R-group with hydrocarbon chain
•Aromatic a.a have benzene ring in the R-group
3-13
3
3-14
Table 3-1, p.62
3
Note these structural features:
1. For 19 of the 20, the -amino group is primary; for
proline, it has secondary amine (called imino acid).
2. With the exception of glycine, amino acids are chiral.
3. Glycine is the smallest amino acid.
4. Isoleucine and threonine contain a second chiral
carbon
5. Amino acids are referred to by three-letter or oneabbreviations. letter
3-15
3 Uncommon Amino Acids
Each example is derived from a common amino
acid by the modification shown in color
+
OH
H3N
I
HO
COONH3
Hydroxylysine
+
+
N
COO-
H H
Hydroxyproline
HO
I
COO-
O
I
I
Thyroxine (T4)
NH3 +
Hydroxylysine and hydroxyproline are found only in a
few connective tissues such as collagen.
Thyroxine (T4)-(modified tyrosine) is found only in the
thyroid gland.
3-16
3
3-17
p.71c
3 AA and neurotransmitters
Two AA are precursors for many neurotransmitters
• Trp serotonin
3-18
3
The high concentration of tryptophan in
milk protein may mildly elevate the
levels of serotonin, which relaxes the
brain. Serotonin is regarded as a chemical that is
responsible for maintaining mood balance, and that a
deficit of serotonin leads to depression.
The tryptophan in milk might make you
sleepy, whereas the tyramine in
cheese should wake you up.
3-19
3
Phe  L-dopa  dopamine  epinephrine 
•
norepinephrine
* Parkinson's
disease,
a degenerative
condition causing
tremor and motor
impairment, is
caused by a loss of
dopamine-secreting
neurons in an area of
the midbrain called
the substantia nigra.
3-20
3 Titration of Amino Acids
Titration of alanine with NaOH
3-21
3 Acidity: -COOH Groups
The average pKa of an -carboxyl group is
2.19,which makes them considerably stronger
acids than acetic acid (pKa 4.76)
the greater acidity of the amino acid carboxyl group is
due to the electron-withdrawing inductive effect of the NH3+ group
The ammonium ion has an
electron-withdrawing
inductive effect
RCHCOOH + H2 O
N H3
+
pK a = 2.19
-
RCHCOO + H3 O
N H3
+
+
3-22
3 Ionization vs pH
• Given the value of pKa of each functional group,
we can calculate the ratio of each acid to its
conjugate base as a function of pH
• Consider the ionization of an -COOH
COOH + H2 O
pK a = 2.00
COO
-
+ H3 O +
• writing the acid ionization constant and rearranging
terms gives
Ka =
[ H 3 O+ ] [ -COO - ]
[ -COO H]
or
[ -COO - ]
[ -COO H]
=
Ka
[ H 3 O+ ]
3-23
3 Ionization vs pH
We can also calculate the ratio of acid to conjugate
base for an -NH3+ group; for this calculation,
assume a value 10.0 for pKa
NH3
+
+ H2 O
pK a = 10.00
NH2
+ H3 O +
writing the acid ionization constant and rearranging
gives
[ -NH 2 ]
[ -NH 3 ]
+
=
Ka
[H 3 O+ ]
3-24
3 Henderson-Hasselbalch
• We have calculated the ratio of acid to conjugate
base for an -carboxyl group and an -amino
group at pH 7.0
• We can do this for any weak acid and its
conjugate base at any pH using the HendersonHasselbalch equation:
pH = -log [H+].
pH = pK a + log
[conjugate base]
[weak acid]
3-25
3 Isoelectric pH
• Isoelectric pH (point), pI: the pH at which the
majority of molecules of a compound in solution
have no net charge
• the pI for glycine, for example, falls midway between
the pKa values for the carboxyl and amino groups
pI = 1 ( p Ka COOH + p Ka N H3 + )
2
= 1 (2.35 + 9.78) = 6.06
2
3-26
3 Peptide bond
• In 1902, Emil Fischer proposed that
proteins are long chains of amino
acids joined by amide bonds to which
he gave the name peptide bonds
• Peptide bond: the special name given
to the amide linkage between the
-carboxyl group of one amino acid
and the -amino group of another.
3-27
3 Peptide bond
3-28
3 Peptides
peptides: the name given to a polymer of amino acids
joined by peptide bonds; they are classified by the
number of amino acid residues in the chain:
dipeptide: a molecule containing two amino acid
residues joined by a peptide bond
tripeptide: a molecule containing three amino acids
joined by peptide bonds
Oligopeptide: few amino acids
polypeptide: a macromolecule containing many amino
acids (normally >100) joined by peptide bonds
protein: a biological macromolecule of molecular weight
5000 g/mol or greater, consisting of one or more
polypeptide chains
3-29
3 Geometry of Peptide Bond
The four atoms of a peptide bond and the two alpha
carbons joined to it, lie in a plane with bond angles of
120° about C and N
To account for this geometry, Linus Pauling proposed
that a peptide bond is most accurately represented as
a hybrid of two contributing structures (resonance)
The hybrid has considerable C-N double bond character
(short) and rotation about the peptide bond is
restricted
:
:
:O
C
:
C
H
(1)
-
C
N
C
:O :
+
C
N
C
H
(2)
3-30
3 Writing Peptides
By convention, peptides are written from the left,
beginning with the free -NH3+ group and ending
with the free -COO- group
the repeat pattern, starting from the N-terminal amino
acid, is N  -carbon  carbonyl carbon etc.
peptide
bonds
+
H 3N
N-terminal
amino acid
S
O
N
H
OH
H
N
O-
O
Ser-Met-Asn
C-terminal
amino acid
O
N H2
O
3-31
3 Writing Peptides
3-32
3 Serylalanine (Ser-Ala)
peptide
bond
HOH2 C H
+
H3N
O- +
O
Serine (Ser)
+
H 3N
O
O-
H CH3
Alanine (Ala)
HOH2 C H H
O
+
N
H 3N
OO H CH
3
Serylalanine (Ser-Ala)
3-33
3 Aspartam( Nutra Sweet)
Artificial Sweetner
3-34
3
3-35
Fig. 3-11, p.72
3 Carnosine is a dipeptide molecule,
made up of the amino acids betaalanine and histidine
It is highly concentrated in
muscle and brain tissues.
It has a number of antioxidant properties that
may be beneficial. Carnosine has been proven
to scavenge reactive oxygen species (ROS) as
well as alpha-beta unsaturated aldehydes
formed from peroxidation of cell membrane fatty
acids during oxidative stress.
3-36
3 Glutathione:
It is γ–glutamyl-L-cysteinylglycine, a tripeptide scavenger for
oxidizing agents (antioxidant)
-
N H3 +
H
N
O
O
O
O
N
H
SH
O- 2e oxidation
2e- reduction
O
Glutathione, GSH
(reduced form)
-
N H3 +
O
O
O
-
H
N
O
O
O
N
H
S
N
H
O
A disulfide
bond
S
O
O-
H
N
O
O-
N H3 +
O
Glutathione, GS-SG
(oxidized form)
3-37
3 Enkephalins
•Pentapeptides found in the brain. They are natural pain killers.
Leucine enkephalin
Tyr-Gly-Gly-Phe-Leu = Y-G-G-F-L
Methionine enkephalin
Tyr-Gly-Gly-Phe-Met = Y-G-G-F-M
3-38
3 Oxytocin & Vasopressin
•Cyclic nanopeptides
•Hormones
+
H3 N -Cy s- Ty r -Ile
S
S
+
H3 N -Cy s- Ty r -Phe
Gln
Cy s-A sn
S
S
O
Pr o-Le u- Gly -C- NH2
Oxytocin
Gln
Cy s-A sn
O
Pr o-A r g- Gly- C-N H2
Vas opress in
3-39
3
Oxytocin has an isoleucine at position 3 and a
leucine at position 8; it stimulates smooth muscle
contraction in the uterus during labor and in the
mammary glands during lactation.
Vasopressin (ADH) has a phenylalanine at position
3 and an arginine at position 8; it stimulates
resorption of water by the kidneys, thus raising
blood pressure.
3-40
3
3-41
p.71a
3
3-42
p.71b
3 Histamine
It is an organic nitrogenous
compound involved in local
immune responses as well as
regulating physiological function
in the gut and acting as a
neurotransmitter. Histamine is
involved in the inflammatory
response
3-43
3
End
Lecture 1
3-44