Chemistry of amino acids

1. CHEMISTRY OF AMINO ACIDS
1
Dr. Nishtha Wadhwa
Department of Biochemistry
St. John’s Medical College

2. Learning Objectives
• General structure of amino acids.
• Classification of amino acids.
• Naming of amino acids.
• Properties of amino acids.
• Reactions of amino acids.
• Qualitative and Quantitative determination.
2

3. Amino acids
Provide the monomer units from which the long
polypeptide chains of proteins are synthesized
 L-amino acids and their derivatives participate in
cellular functions
There are 20 amino acids for which DNA codons
are known.
Short polymers of amino acids called peptides
perform prominent roles in the neuroendocrine
system as hormones, hormone-releasing factors,
neuromodulators, or neurotransmitters.
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4. GENERAL STRUCTURE OF AN AMINO ACID
All amino acid (except Proline) have
 a carboxyl group,
 an amino group and
 a distinctive side chain bonded to the alpha
carbon atom, which varies between the 20
different AA.
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5. • At physiological pH the carboxyl group is dissociated
forming the negatively charged carboxylate ion(-COO
-
), and the amino group is protonated(-NH3
+).
• Most of the amino acids (except proline) are alpha
amino acids, which means that the amino group is
attached to the same carbon atom to which the
carboxyl group is attached.
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6. 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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7. 1) Classification based on structure
They are classified in three broad categories:
 Mono amino mono carboxylic acid
It is further subdivided in 5 groups:
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Groups: Examples:
• Simple amino acids Glycine, Alanine
• Branched chain amino acids Valine, Leucine, Isoleucine
• Hydroxy amino acids Serine, Threonine
• Sulphur-containing amino acids Cysteine, Methionine
• Amino acids with amide group Asparagine, Glutamine
I. Aliphatic Amino Acids:

8.  Mono amino dicarboxylic acid
Example :aspartic acid, glutamic acid
 Di /poly amino mono carboxylic acid
Example : Lysine, Arginine
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9. 1) Classification based on structure
I. Aliphatic Amino Acids:
 Mono-amino mono-carboxylic acids:
 Simple amino acids
Small R-group of Glycine : minimum of steric
hindrance ,fits into crowded regions of many peptide
chains. E.g. Collagen
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10.  Branched chain amino acids
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 OH group-containing amino acids

11.  Sulfur-containing amino acids
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 Amide group-containing amino acids

12. 1) Classification based on structure
I. Aliphatic Amino Acids:
 Mono-amino di-carboxylic acids:
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13. 1) Classification based on structure
I. Aliphatic Amino Acids:
 Di- basic mono-carboxylic acids
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14. 1) Classification based on structure
II. Aromatic amino acids
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15. 1) Classification based on structure
III. Heterocyclic Amino Acids
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16. 1) Classification based on structure
IV. Imino acid- Proline
Has a rotationally constrained rigid-ring structure.
reduces structural flexibility of polypeptides
E.g. Collagen
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17. 1)Classification based on structure
V. Derived Amino Acids:
 Derived amino acids found proteins:
e.g.: Hydroxy-proline, hydroxy-lysine
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18.  Derived amino acids not found in proteins:
e.g.: Ornithine, Citrulline, Homocysteine
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19.  Non-α-amino acids
e.g.: β-alanine, γ-amino butyric acid
(GABA)
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20. Special groups in amino acids
 Arginine- Guanidinium group
Phenyl Alanine- Benzene group
 Tyrosine- Phenol group
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21. Tryptophan- Indole group
 Histidine- Imidazole group
Proline- Pyrrolidine
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22. 2) Classification based on side chain characters
• Hydropathy Index
• Side chains of Hydrophobic amino acids tend to
cluster, to exclude water(hydrophobic effect),
stabilizing protein, whereas others participate in
hydrogen bonding.
• Cysteine can form disulfide bonds whereas
charged amino acids can form ionic bonds.
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23. 2) Classification based on side chain characters
A. Amino acids with a non-polar side-chain:
e.g.: Glycine, Alanine, Valine, Leucine, Isoleucine,
Methionine, Phenylalanine, Tryptophan, Proline
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24. • Hydrophobic.
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25. B) Amino acids with uncharged or non-ionic side-
chain: e.g. Serine, Threonine, Tyrosine, Cysteine,
Asparagine and Glutamine.
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26. C) Amino acids with a charged 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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27. Importance of hydropathy index
• Sickle cell anemia
• Replacement of polar
glutamate with nonpolar
valine at the sixth position
in the β subunit of
hemoglobin.
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28. 3) Classification based on nutritional requirements
I. Essential amino acids:
Valine, Isoleucine, Leucine, Lysine, Methionine,
Threonine, Tryptophan and Phenylalanine.
II. Semi-essential amino acids:
Arginine and Histidine.
III. Non-essential amino acids:
Glycine, Alanine, and the other remaining amino
acids.
IV. Conditionally essential amino
Arginine, Glycine, Cysteine,Tyrosine, Proline,
Glutamine and Taurine.
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29. 3) Classification based on metabolic fate
I. Both glucogenic and ketogenic amino acids:
Lysine, Isoleucine, Tyrosine, Phenylalanine and
Tryptophan
II. Purely Ketogenic amino acids:
Leucine
III. Purely Glucogenic amino acids:
The remaining 14 amino acids are glucogenic.
Alanine, valine ,serine, threonine, glycine,
methionine, asparagine, glutamine, cysteine,
cystine, aspartic acid, glutamic acid, histidine
and arginine.
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30. NON STANDARD AMINO ACIDS
 20 Primary or Standard amino acids.
Seleno cysteine is the 21st Amino Acid
The other are Pyroglutamate and Pyrrolysine.
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31. NAMING OF AMINO ACIDS
 Trivial or common names
E.g. Glycine( Greek glykos, “sweet”)
 Three letter code: Generally first three letters of
amino acid name.
 One letter code:
Unique first letter(CHIMSV)
 Cysteine- Cys- C
Priority of commonly occurring amino acids in
proteins (AGLPT)
 Leucine is more common than Lysine
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32. Phonetic similarity (RFYW)
 aRginine
 Fenylalanine
 tYrosine
 TWiptophan
Letters found within or suggested by name (DNEQ)
 AsparDic
 AsparagiNe
 GlutamEke
 Q-tamine
Letters close to initial letter
Lysine – K (near L)
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33. Abbreviation
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34. PROPERTIES OF AMINO ACIDS
Physical properties-
Colorless
Crystalline
May be sweet(Glycine, Alanine, Valine),
tasteless(Leucine) or bitter(Arginine,
Isoleucine). Aspartame- An artificial
sweetener contains Aspartic acid and Phenyl
alanine.
High melting point
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35. Isoelectric point
Amino acids are ampholytes.
Neutral zwitterions
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.
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Due to no net charge, there is no
electrophoretic mobility at Isoelectric pH.
Solubility and Buffering capacity will be
minimum at isoelectric pH.

36. Isoelectric point
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37. 37
Titration of acetic acid

38. Titration of Glycine
For mono amino mono
carboxylic amino
acids-
pI = pK1+pK2
2
The buffering action is
maximum in and
around pK1or at pK2
but is minimum at pI
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39. 39

40. 40

41. • Sorensen titration
• Amino acids cannot be exactly titrated.
• This is because hydrogen ions released by
ionization of carboxyl group are partly taken
up by the amino group.
• To circumvent this problem, excess
formaldehyde is added to the solution, which
converts amino group into neutral dimethylol
derivative. Thereafter, titration can be
completed to the end.
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42. 42

43. pKa of some amino acids
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44. 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.
Glycine is exceptional because there are two
hydrogen substituents at the α carbon, thus it is
optically inactive.
Amino acids with asymmetric centre at the α carbon
can exist in two forms, D and L forms that are mirror
images of each other and are called Enantiomers.
All amino acids found in proteins are of L-
configuration
D- amino acids are found in some antibiotics and in
bacterial cell walls.
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45. L & D isomers of amino acids
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46. Absorbance
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47. REACTIONS OF AMINO ACIDS
1) Reactions due to amino group
2) Reactions due to carboxyl group
3) Reactions due to side chain
4) Reaction due to both amino and carboxyl
groups
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48. Reactions due to amino group
Oxidative deamination-α amino group is removed and
corresponding α-keto acid is formed. α-keto acid produced
is either converted to glucose or ketone bodies or is
completely oxidized.
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49. Transamination-Transfer of an α amino group
from an amino acid to an α keto acid to form a
new amino acid and a corresponding keto
acid.
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50. Formation of carbamino compound
CO2 binds to α amino acid on the globin chain of
hemoglobin to form carbamino hemoglobin
The reaction takes place at alkaline pH and serves as a
mechanism for the transfer of Carbon dioxide from the
tissues to the lungs by hemoglobin.
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51. Reactions due to carboxyl group
1) Decarboxylation- Amino acids undergo alpha
decarboxylation to form corresponding amines.
Examples-
Glutamic acid GABA
Histidine Histamine
Tyrosine Tyramine
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52. 2)Formation of amide linkage
• Non α carboxyl group of an acidic amino acid reacts
with ammonia by condensation reaction to form
corresponding amides
• Aspartic acid Asparagine
• Glutamic acid Glutamine
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53. Reactions due to side chains
1) Ester formation
 OH containing amino acids e.g. serine, threonine
can form esters with phosphoric acid in the
formation of phosphoproteins.
 OH group containing amino acid can also form:
Glycosides – by forming
O- glycosidic bond with
carbohydrate residues.
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54. 2) N-glycosidic linkage
• Amide group of Glutamine and Asparagine
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55. 2) Reactions due to SH group (Formation of
disulphide bonds)
Cysteine has a sulfhydryl group( SH) group and
can form a disulphide (S-S) bond with another
cysteine residue.
 The dimer is called Cystine
Two cysteine residues can connect two
polypeptide chains by the formation of interchain
disulphide chains.
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56. Formation of disulphide bond
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57. 3)Transmethylation
The methyl group of Methionine can be
transferred after activation to an acceptor for
the formation of important biological
compounds.
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58. 4)Reactions due to both amino & carboxyl groups
Formation of peptide bond
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59. • Resonance hybrid
• 50% double bond character
• Rigid
• Trans-peptide bonds are always found in proteins
except where there are proline residues.
• In proline the side chain is linked to its α-amino group,
and the cis and trans peptide bonds with the proline α-
imino group have near equal energies. The
configuration of the peptide bond actually found for a
proline in a protein will depend on the specific forces
generated by the unique folded three-dimensional
structure of the protein molecule.
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60. Functions of AA
 Proteins and peptides
 Gluconeogenesis
 Methionine: Transmethylation
 Detoxication: Glycine; Methionine; Cysteine
 Specialized biological products:
 Nicotinamide, Serotonin and melatonin are synthesized from
Tryptophan
 Melanin, thyroid hormone, catecholamines are synthesized
from Tyrosine
 GABA (neurotransmitter) is synthesized from Glutamic acid
 Sphingosine from Serine
 Histamine from Histidine
 Nitric oxide, a smooth muscle relaxant is synthesized from
Arginine.
 Act as precursors for haem, creatine and glutathione,
Porphyrins, purines and pyrimidines 60

61. Methods of separation/identification
1) Methods of Fischer, Dakin, Van slyke and
others.
Fisher: Fractional distillation of ethyl esters
Dakin: Butyl alcohol
Van slyke :
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62. 2) Electrodialysis : Based on charge
3) Isotopic Dilution
4)Chromatography
5) Microbiological: Use of amino acids by
organisms for growth
6) Enzymatic: Decarboxylation , release of CO2
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63. Colour reactions of amino acids
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S.No. Test Significance
1) Ninhydrin reaction Given by all Alpha amino acids
2) Xanthoproteic test Given by aromatic amino acids
3) Millon’s test Confirmatory test for Tyrosine
4) Biuret test Not given by free amino acids
5) Sakaguchi test Given by Arginine
6) Hopkins Cole
reaction
Confirmatory test for Tryptophan
7) Lead acetate test Given by cysteine and cystine but
not given by Methionine
8) Nitroprusside
reaction
Given by SH group containing amino
acids

64. Summary
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65. REFERENCES
• Vasudevan Textbook of Biochemistry -7th edition
• Lehninger Principles of Biochemistry - 7th Edition
• Harper’s Illustrated Biochemistry 30th Edition
• Lippincott’s Illustrated Reviews :Biochemistry 6th
Edition
• Debajyoti Das: Biochemistry 14th Edition
• Devlin, Thomas M: Textbook of Biochemistry :
With Clinical Correlations- 4th Edition.
• Cantrow, Schepartz: Biochemistry 4th edition
THANK YOU 65