1 1chemistryofaminoacids 7 fin do PDF · Hydroxyl group containing amino acids: serine, ... contain...

2016-11-06

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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”.

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Amino Acids

Each amino acid has 4 different groups attached

to α- carbon ( which is C-atom next to COOH).

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R

αα

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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.

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CH

COO

H 3 N

CH 2

CH 2

CH 2

CH 2

NH 3

αβγδε

Amino AcidsEach amino acid (except proline) has 4 groups:

� amino group,

�COOH group,

�Hydrogen atom

�and side Chain (R)

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Amino AcidsAt 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

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Amino Acid Structure• Amino acids contain two functional groups,

a protonated amine and carboxylic acid in the form

of a carboxylate ion.

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• The side chain is unique for each amino acid.

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.

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L (S) –amino acid D (R)- amino acid


• 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.


The only amino acid not exhibiting chirality is

glycine. There are two hydrogen substituents

at the α-carbon, thus it is optically inactive.

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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)

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C COOH

H

NH2

CCH2

CH3

H

CH3**

isoleucine

C COOH

H

NH2

CCH3

OH

H

**

threonine

Threonine and isoleucine have 2 chiral carbons


• 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

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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

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Aliphatic Amino Acids:

1. Classification based on structure

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

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Aliphatic Amino Acids:

Aromatic Amino Acids:

Phenylalamime, tyrosine, tryptophan, histidine,

proline

Aliphatic Amino Acids

Glycine (Gly, G) Alanine (Ala, A) Valine (Val, V)

Leucine (Leu, L) Isoleucine (Ile, I)

Branched chain amino acids:

Valine, Leucine and Isoleucine

Valine R= isopropyl group

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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- carbon19

Leucine (Leu, L) Isoleucine (Ile, I)

Neutral, hydroxy amino acids (-OH group-containing

amino acids): Serine and Threonine

Serine (Ser, S) Threonine (Thr, T)


Sulfur-containing amino acids:Cysteine and Methionine


Cysteine (Cys, C) Methionine (Met, M)

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Amide group-containing amino acids:

Asparagine and Glutamine


Asparagine (Asn, N) Glutamine (Gln, Q)

Mono-amino di-carboxylic acids:

Aspartic acid and Glutamic acid


Aspartate (Asp, D) Glutamate (Glu, E)

Di-/Poly- amino mono-carboxylic acids:

Lysine and Arginine


Lysine (Lys, K) Arginine (Arg, R)

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Heterocyclic Amino Acids: Phenylalanine and tyrosine

Aromatic Amino Acids

Phenylalanine (Phe, F) Tyrosine (Tyr, Y)

Heterocyclic Amino Acids: Tryptophan and Histidine


Tryptophan (Trp, W) Histidine (His, H)

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)

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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.


� Arginine- Guanidinium group

� Phenylalanine- Benzene group

� Tyrosine- Phenol group


� Tryptophan- Indole group

� Histidine- Imidazole group

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4

3

5

Histidine

Indole

Imidazole

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� Proline- Pyrrolidine

Proline has a secondary amino group, hence

it is an imino acid.

Pyrrolidine Proline

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2. Classification based on side chain characters

Nonpolar R = H, CH3, alkyl groups, aromatic ringsO

Polar ll

R = –OH, –SH, –C–NH2,

(polar groups with –O-, -SH, -N-)

Polar/Acidic

R = -COOH

Polar/ Basic

R = –NH2


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.

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Amino acids with a polar but uncharged side-

chain:

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.


Amino acids with a polar but uncharged side-

chain

• 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.

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Amino acids with a polar but uncharged side chain

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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.

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Amino acids with a charged side-chain

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Test – example 1

Identify each as (1) polar or (2) nonpolar

A. NH2–CH2–COOH (Glycine)

OH|

CH 2|

B. NH2–CH–COOH (Serine)

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)

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Alanine

Asparagine

Aspartic Acid

Cysteine

Glutamic acid

Glutamine

Glycine

Proline

Serine

Tyrosine

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.


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:

4. Classification based on on metabolic fate

Purely Glucogenic

amino acids

Purely

Ketogenic

amino acids

Both glucogenic

and ketogenic

amino acids

Glycine, Alanine,Arginine

Aspargine, Aspartic acid

Cysteine,

Glutamine, Glutamic acid

Histidine, Proline,

Methionine, Serine

Threonine, Valine

Leucine and

Lysine

Isoleucine,

Tyrosine,

Phenylalanine,

Tryptophan

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Fates of carbon

skeleton of amino

acids

Naming of Amino acids

Each amino acid has three letter (code) and

one letter (Symbol) abbreviations-

1) 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)

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Amino acid abbreviations

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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.


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.

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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

CH COOHR

NH3+

CH COO - R

NH3+

zwitterionic form

NEUTRAL SOLUTION

pH = pI

CH COO - R

NH2

anionic form

negative ion

BASIC SOLUTION

pH greater than pI

cationic form

positive ion

ACIDIC SOLUTION

pH lower than pI

H+OH-

pH 13 Net charge -1 pH 7 Net charge 0 pH 1 Net charge +1

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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

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Isoelectric point

Amino Acids as Acids and Bases

Isoelectric point

Amino Acids as Acids and Bases

• Ionization of the –NH 2 and the –COOH group• Zwitterion has both a + and – charge• Zwitterion is neutral overall

NH2–CH2–COOH H3N+–CH2–COO–

glycine Zwitterion/dipolar ionof glycine

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Test – example 2

CH3 CH3

+

H3N–CH–COOH H2N–CH2–COO–

(1) (2)

Select from the above structures

A. Alanine in base.

B. Alanine in acid.

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1) Strecker Synthesis

SYNTHESIS OF AMINO ACIDS

The Strecker Synthesis is a preparation of

α-aminonitriles, which are intermediates for the

synthesis of amino acids via hydrolysis of the nitrile.

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CH3 CH2 COOH

propionic acid

1. Br2, PBr3

2. H2OCH33

CH2

COOH1

Br

NH3 excessCH33

CH2

COOH1

NH2

2-bromopropionic acid 2-aminopropionic acid

D-Alanine and L-Alanine

(1:1)

2) Bromination of a carboxylic acid


The bromoacid are conveniently prepared from

carboxylic acids by reaction with PBr3 .

Amination of alpha-bromocarboxylic acids provides a

straight forward method for preparing alpha-

aminocarboxylic acids.

Hell-Volhard-Zelinsky Reaction

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NaBH4

CH33

CH2

COOH1

NH2

2-aminopropionic acid

D-Alanine and L-Alanine (1:1)

CH3 C COOH

O

pyruvic acid

(and alpha- keto acid)

NH3

3) Reductive amination of α-keto acids


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CH

NH2

CO

OHCH2CH2C

OH

O

+ NaOH + H2OCH

NH2

CO

OHCH2CH2C

O

O

Na

sodium glutamate

(main ingredient of Vegeta)

1) Amino acids are ampholytes - they can act as

either an acid or a base

reaction with a base (reaction of acidic –COOH

group)

Reactions of AA

sodium glutamate

(main ingredient of Vegeta)

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CH2

NH2

CO

OH + HCl CH2

NH3+

CO

OH

ammonium salt of GlycineCl-

reaction with an acid (reaction of basic –NH2 group)

Reactions of AA

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CH2

NH2

CO

OH + CH2

NH2

CO

O CH2 CH3

C2H5HO

ester bond

+ H2O

ethyl ester of Glycine

conc. H2SO4

2) esterification reaction (reaction of –COOH group)

Reactions of AA

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CH3 CH COOH

NH2

Alanine

+ HNO2 CH3 CH COOH

OH+ N2 + H2O

an amino acid a hydroxy acid

Lactic acid

* *

3) dezamination of amino acids (reaction of –NH2 group) –

reaction with nitrous acid

Reactions of AA

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4) decarboxylation reaction (reaction of –COOH group) –

for neutral and basic amino acids

CH2 CH COOH

NH2NH

N

*

histaminehistidine

CH2 CH2

NH2NH

N

+ CO2

Reactions of AA

CH22

C1

CH23

CH24

O

OHN

H H

C

NH

CH22

CH23

CH24

O

+ H2O

gamma-Lactam

(a cyclic amide)

alpha betagamma

NHO

5) condensation reaction of (gamma) γ-amino acids (reaction between –NH2 and –COOH of the same molecule)

Lactam rings are found in antibiotics’ molecules ( i.e. in penicillin).

Reactions of AA

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6767

6) acylation reaction (reaction of –NH2 group)

C

O

NH2CH2

OH+ CH3 C

Cl

O CH3 CO

C

O

NHCH2

OH + ClH

acethyl chlorideN-acethylglycine

Reactions of AA

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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.

Color reactions of amino acids

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Color reactions of amino acids

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