Download 1 1chemistryofaminoacids 7 fin do PDF

2016-11-06
Introduction to amino acids
and proteins
Amino Acids
• Amino Acids are the building units of proteins.
Proteins are polymers of amino acids linked
together by “ Peptide bond”.
2
Amino Acids
Each amino acid has 4 different groups attached
to α- carbon ( which is C-atom next to COOH).
α
R
3
1
2016-11-06
Amino Acid Structure
• Amino acid carbons are named in sequence using the
Greek alphabet (α, β, γ, δ, ε) starting at the carbon
between the carboxyl and amino groups.
H 3N
COO
CH
CH 2
CH 2
CH
CH
NH
α
β
γ
2
δ
2
ε
3
4
Amino Acids
Each amino acid (except proline) has 4 groups:
amino group,
COOH group,
Hydrogen atom
and side Chain (R)
5
Amino Acids
At physiological pH (7.4), the carboxyl group
(-COOH) is dissociated forming the negatively
charged carboxylate ion(-COO-), and the amino
group is protonated(-NH3+) forming positively
charged ion (NH3+) forming Zwitter ion
6
2
2016-11-06
Amino Acid Structure
• Amino acids contain two functional groups,
a protonated amine and carboxylic acid in the form
of a carboxylate ion.
• The side chain is unique for each amino acid.
7
Optical properties of amino acids
The α carbon of each amino acid is attached
to four different groups and is thus a chiral
or optically active carbon atom.
• When
drawing
the
Fischer
projection,
the carboxylate group is at the top of the structure
and the side chain (R group) is at the bottom.
• The protonated amine group can be on the left-hand
side (L form) or right-hand side (D form) of the
structure.
9
3
2016-11-06
Optical properties of amino acids
• Amino acids with asymmetric centre at the
α carbon can exist in two forms, L and D
forms that are mirror images of each
other and are called Enantiomers.
L (S) –amino acid
D (R)- amino acid
Optical properties of amino acids
The only amino acid not exhibiting chirality is
glycine. There are two hydrogen substituents
at the α-carbon, thus it is optically inactive.
Stereochemistry of amino acids
• 19 of the 20 common amino acids have a chiral α-carbon
atom (Gly does not)
• Threonine and isoleucine have 2 chiral carbons each
(4 possible stereoisomers each)
• Mirror image pairs of amino acids are designated L (levo)
and D (dextro)
12
4
2016-11-06
Threonine and isoleucine have 2 chiral carbons
isoleucine
H
H3C
CH2 C*
threonine
H
C*
H
COOH
H3C
CH3 NH2
H
C*
C*
OH
NH2
COOH
13
Optical properties of amino acids
• All amino acids found in proteins are of
L-configuration
• D-amino acids occur in nature, but not in
proteins.
• D- amino acids are found in some
antibiotics and in bacterial cell walls.
Classification of amino acids
Amino acids can be classified in 4 ways:
1. Based on structure
2. Based on the side chain characters
3. Based on nutritional requirements
4. Based on metabolic fate
5
2016-11-06
1. Classification based on structure
Aliphatic Amino Acids:
They are classified in three broad categories:
I. Mono amino mono carboxylic acid
(further subdivided in 5 groups):
1. Simple amino acids: glycine, alanine
2. Branched chain amino acids: valine,leucine,isoleucine
3. Hydroxyl group containing amino acids: serine, threonine
4. Sulphur containing amino acids: cysteine, methionine
5. Amide group containing amino acids: asparagine, glutamine
16
Aliphatic Amino Acids:
They are classified in three broad categories:
II. Mono amino dicarboxylic acid
Example: aspartic acid, glutamic acid
III. Di /poly amino mono carboxylic acid
Example: lysine, arginine
Aromatic Amino Acids:
Phenylalamime, tyrosine, tryptophan, histidine,
proline
17
Aliphatic Amino Acids
Glycine (Gly, G)
Alanine (Ala, A)
Valine (Val, V)
Branched chain amino acids:
Valine, Leucine and Isoleucine
Valine
Leucine (Leu, L)
R= isopropyl group
Isoleucine (Ile, I)
18
6
2016-11-06
Aliphatic Amino Acids
Leucine (Leu, L)
Isoleucine (Ile, I)
Branched chain amino acids:
R is isobutyl in both leucine and isoleucine but
branching is different:
• in leucine → branching occurs on γ carbon
• in isoleucine→ branching occurs on β- carbon
19
Aliphatic Amino Acids
Neutral, hydroxy amino acids (-OH group-containing
amino acids): Serine and Threonine
Serine (Ser, S)
Threonine (Thr, T)
Aliphatic Amino Acids
Sulfur-containing amino acids:
Cysteine and Methionine
Cysteine (Cys, C)
Methionine (Met, M)
7
2016-11-06
Aliphatic Amino Acids
Amide group-containing amino acids:
Asparagine and Glutamine
Asparagine (Asn, N)
Glutamine (Gln, Q)
Aliphatic Amino Acids
Mono-amino di-carboxylic acids:
Aspartic acid and Glutamic acid
Aspartate (Asp, D)
Glutamate (Glu, E)
Aliphatic Amino Acids
Di-/Poly- amino mono-carboxylic acids:
Lysine and Arginine
Lysine (Lys, K)
Arginine (Arg, R)
8
2016-11-06
Aromatic Amino Acids
Heterocyclic Amino Acids: Phenylalanine and tyrosine
Phenylalanine (Phe, F)
Tyrosine (Tyr, Y)
Aromatic Amino Acids
Heterocyclic Amino Acids: Tryptophan and Histidine
Tryptophan (Trp, W)
Histidine (His, H)
Aromatic Amino Acids
Imino acid- Proline
In proline, amino group enters in the ring formation being
α-imino group so proline is an α-imino acid rather than α-amino
acid
Proline (Pro, P)
9
2016-11-06
Special groups in amino acids
Arginine- Guanidinium group
Phenyl Alanine- Benzene group
Tyrosine- Phenol group
Tryptophan- Indole group
Histidine- Imidazole group
Proline- Pyrrolidine
Proline has a secondary amino group, hence
it is an imino acid.
Special groups in amino acids
Arginine- Guanidinium group
Phenylalanine- Benzene group
Tyrosine- Phenol group
Special groups in amino acids
Indole
Tryptophan- Indole group
Histidine- Imidazole group
4
5
3
1
2
Imidazole
Histidine
10
2016-11-06
Special groups in amino acids
Proline- Pyrrolidine
Proline has a secondary amino group, hence
it is an imino acid.
Pyrrolidine
Proline
2. Classification based on side chain characters
Nonpolar R = H, CH3, alkyl groups, aromatic rings
O
Polar
ll
R = –OH, –SH, –C–NH2,
(polar groups with –O-, -SH, -N-)
Polar/Acidic
R = -COOH
Polar/ Basic
R = –NH2
32
2. Classification based on side chain characters
Amino acids with a non-polar side-chain:
e.g.: Glycine, Alanine, Valine, Leucine, Isoleucine,
Methionine, Phenylalanine, Tryptophan, Proline
• Each of these amino acids has a side chain that
does not bind or give off protons or participates
in hydrogen or ionic bonds.
• Side chains of these amino acids can be thought
of as “Oily” or lipid like, a property that promotes
hydrophobic interactions.
11
2016-11-06
34
2. Classification based on side chain characters
Amino acids with a polar but uncharged sidechain:
Serine, Threonine, Tyrosine, Cysteine,
Asparagine and Glutamine
These amino acids are uncharged at neutral pH,
although the side chains of Cysteine and
Tyrosine can lose a proton at an alkaline pH.
2. Classification based on side chain characters
Amino acids with a polar but uncharged sidechain
• Serine , Threonine and Tyrosine each contains
a polar hydroxyl group that can participate in
hydrogen bond formation.
• Side chains of Asparagine and Glutamine
contain a carbonyl group and amide group,
they can also participate in hydrogen bond
formation.
12
2016-11-06
Amino acids with a polar but uncharged side chain
37
2. Classification based on side chain characters
Amino acids with a charged polar side-chain
a) Amino acids with a positively charged side-chain:
The basic amino acids- Lysine, Arginine and
Histidine
b) Amino acids with a negatively charged side-chain:
The acidic amino acids- Glutamic acid and Aspartic
acid
They are hydrophilic in nature.
Amino acids with a charged side-chain
39
13
2016-11-06
Test – example 1
Identify each as (1) polar or (2) nonpolar
A. NH2–CH2–COOH
(Glycine)
OH
|
CH 2
|
B. NH2–CH–COOH
(Serine)
40
3. Classification based on nutritional requirements
I. Essential amino acids:
These amino acids cannot be synthesized in
the body and have to be present essentially in
the diet.
Phenylalanine, Isoleucine, Leucine, Lysine,
Methionine, Threonine, Tryptophan and
Valine
FIL2M T2V
3. Classification based on nutritional requirements
II. Semi-essential amino acids:
These amino acids can be synthesized in the
body but the rate of synthesis is lesser than
the requirement(e.g. during growth, repair or
pregnancy) Arginine and Histidine
(Arg & His)
14
2016-11-06
3. Classification based on nutritional requirements
III. Non-essential amino acids:
These amino acids are
synthesized in the body,
thus their absence in the
diet does not adversely
affect the growth.
Alanine
Asparagine
Aspartic Acid
Cysteine
Glutamic acid
Glutamine
Glycine
Proline
Serine
Tyrosine
4. Classification based on on metabolic fate
1- Purely Ketogenic:
Leucine and Lysine are purely ketogenic because it will enter
into the metabolic pathway of ketogenesis.
2- Ketogenic and Glucogenic:
Isoleucine, Phenylalanine, Tyrosine and Tryptophan
During metabolism, part of the carbon skeleton of these
amino acids will enter the fatty acid metabolic pathway and
the other part into glucose pathway.
3- Purely Glucogenic:
All the remaining 14 amino acids are purely glucogenic as
they enter only into the glucogenic pathway.
4. Classification based on on metabolic fate
The carbon skeleton of amino acids can be used either
for glucose production or for the production of ketone
bodies, based on that:
Purely Glucogenic
amino acids
Purely
Ketogenic
amino acids
Glycine, Alanine,Arginine Leucine and
Lysine
Aspargine, Aspartic acid
Cysteine,
Glutamine, Glutamic acid
Histidine, Proline,
Methionine, Serine
Threonine, Valine
Both glucogenic
and ketogenic
amino acids
Isoleucine,
Tyrosine,
Phenylalanine,
Tryptophan
15
2016-11-06
Fates of carbon
skeleton of amino
acids
Naming of Amino acids
Each amino acid has three letter (code) and
one letter (Symbol) abbreviations1) Unique first letter
• Cysteine- Cys- C
• Histidine- His- H
2) Priority of commonly occurring amino acids
• Alanine- Ala- A (Preference over Aspartate)
• Glycine- Gly-G (Preference over Glutamate)
Naming of Amino acids
3) Similar sounding names- Some one letter
symbols sound like the amino acids
• Tryptophan – W (Twyptophan)
• Phenylalanine – F
4) Letters close to initial letter
• Aspartate- Asx- B (near A)
• Lysine Lys- K (near L)
16
2016-11-06
Amino acid abbreviations
49
Properties of amino acids
Physical properties
• Colorless, form white crystals
• High melting point (More than 2000C)
Solubility
Most of amino acids are soluble in water, acids,
alkalis but insoluble in organic solvents.
Cysteine, aromatic and acidic amino acids are
slightly soluble in water.
Properties of amino acids
Taste Amino acids are:
tasteless (e.g. Leucine, Lys, Trp, Asp, Cys),
sweet (e.g. Gly, Ala, Val, Ser),
bitter (Arginine, Isoleucine, Tyr, Ile, Leu)
If amino acids change their D-L configuration, in
general their taste is changing as well.
• Aspartame - An artificial sweetener contains
Aspartic acid and Phenylalanine.
17
2016-11-06
Properties of amino acids
Smell
• Most of amino acids are odorless, except for:
Cysteine and Methionine (an odour of sulfur
derivatives);
• Glutamic acid (a flavour of a broth,
it is broadly used in Chinese cousine,
enhances taste and smell of meals).
• A flavour of a bread comes from products of a
reaction of proline with glucose.
Isoelectric point
• Amino acids can exist as ampholytes or
zwitterions in solution, depending upon pH of
the medium.
• The pH at which the amino acids exist as
zwitterions, with no net charge on them is called
Isoelectric pH or Isoelectric point.
• In acidic medium, the amino acids exist as
cations
• In alkaline medium, they exist as anions.
Isoelectric point
pH 13 Net charge -1
pH 7 Net charge 0
H+
OHR
CH
COO -
NH2
anionic form
negative ion
BASIC SOLUTION
pH greater than pI
pH 1 Net charge +1
R
CH
NH3
COO +
zwitterionic form
NEUTRAL SOLUTION
pH = pI
R
CH
COOH
+
NH3
cationic form
positive ion
ACIDIC SOLUTION
pH lower than pI
18
2016-11-06
Isoelectric point
Due to no net charge, there is no
electrophoretic mobility at Isoelectric pH.
Solubility and buffering capacity are also
minimum at Isoelectric pH
Isoelectric point
Amino Acids as Acids and Bases
• Ionization of the –NH2 and the –COOH group
• Zwitterion has both a + and – charge
• Zwitterion is neutral overall
NH2–CH2–COOH
glycine
H3N+–CH2–COO–
Zwitterion/dipolar ion
of glycine
56
Test – example 2
CH3
CH3
+
H3N–CH–COOH
(1)
H2N–CH2–COO–
(2)
Select from the above structures
A. Alanine in base.
B. Alanine in acid.
57
19
2016-11-06
SYNTHESIS OF AMINO ACIDS
1) Strecker Synthesis
The Strecker Synthesis is a preparation of
α-aminonitriles, which are intermediates for the
synthesis of amino acids via hydrolysis of the nitrile.
58
SYNTHESIS OF AMINO ACIDS
2) Bromination of a carboxylic acid
CH3 CH2 COOH
propionic acid
1. Br2, PBr3
2. H2O
CH3 CH
3
2
COOH
Hell-Volhard-Zelinsky Reaction
NH3 excess
CH3 CH
1
3
Br
COOH
2
1
NH2
2-aminopropionic acid
2-bromopropionic acid
D-Alanine and L-Alanine
(1:1)
The bromoacid are conveniently prepared from
carboxylic acids by reaction with PBr3 .
Amination of alpha-bromocarboxylic acids provides a
straight forward method for preparing alpha59
aminocarboxylic acids.
SYNTHESIS OF AMINO ACIDS
3) Reductive amination of α-keto acids
H3C
C
COOH
O
pyruvic acid
(and alpha- keto acid)
NH3
CH3 CH
3
NaBH4
2
COOH
1
NH2
2-aminopropionic acid
D-Alanine and L-Alanine (1:1)
60
20
2016-11-06
Reactions of AA
1) Amino acids are ampholytes - they can act as
either an acid or a base
reaction with a base (reaction of acidic –COOH
group)
O
C CH2
CH2 CH
HO
NH2
O
C
OH
+
O
C CH2
NaOH
CH2 CH
NaO
NH2
O
C
OH
+
H2O
glutamate
sodiumsodium
glutamate
(main
ingredient of Vegeta)
(main ingredient of Vegeta)
61
Reactions of AA
reaction with an acid (reaction of basic –NH2 group)
O
CH 2
O
C
OH
NH 2
+
CH 2
HCl
C
OH
Clammonium salt of Glycine
NH 3
+
62
Reactions of AA
2) esterification reaction (reaction of –COOH group)
ester bond
O
CH2
NH2
C
OH
+
conc. H2SO4
HO
C 2 H5
O
CH2
NH2
C
O
CH2
CH3
+
H2 O
ethyl ester of Glycine
63
21
2016-11-06
Reactions of AA
3) dezamination of amino acids (reaction of –NH2 group) –
reaction with nitrous acid
*
CH
H3C
+
COOH
HNO2
*
CH
H3C
NH2
COOH
OH
an amino acid
a hydroxy acid
Alanine
Lactic acid
+
N2
+
H2 O
64
Reactions of AA
4) decarboxylation reaction (reaction of –COOH group) –
for neutral and basic amino acids
N
N
*
CH
CH2
N
H
COOH
NH2
CH2
CH2
N
H
+
CO 2
NH2
histidine
histamine
65
Reactions of AA
5) condensation reaction of (gamma) γ-amino acids
(reaction between –NH2 and –COOH of the same molecule)
beta
gamma
alpha
CH 2
O
CH 2
4
3
CH 2
2
C
H
2
H 2C
1
OH
N
H
CH 2
C
O
3
H 2C
NH
+
H2O
4
gamma-Lactam
(a cyclic amide)
NH
O
Lactam rings are found in antibiotics’ molecules ( i.e. in penicillin).
66
22
2016-11-06
Reactions of AA
6) acylation reaction (reaction of –NH2 group)
Cl
O
H 2N
C
CH2 OH
+
H3C
O
NH
C
O
acethyl chloride
H3C
C
O
C
CH2 OH
+
HCl
N-acethylglycine
67
Color reactions of amino acids
The Ninhydrin Reaction
In addition to these common reactions of amines and
carboxylic acids, common alpha-amino acids, except
proline, undergo a unique reaction with the
triketohydrindene hydrate known as ninhydrin.
Among the products of this unusual reaction is a purple
colored imino derivative, which provides as a useful
color test for amino acids, most of which are colorless. A
common application of the ninhydrin test is the
visualization of amino acids in paper chromatography.
68
Color reactions of amino acids
69
23