Classification of aminoacids

2. AMINOACID CLASSIFICATION
BY
DR SHAMIM AKRAM
Ass.P AIMC

3. CLASSIFICATION OF AMINOACIDS
• Depending upon source (protein/non-protein)
• Standard(primary) AminoAcids:
• These are 20 amino acids that take part in the
formation of all types of proteins.Each one of these
has genetic codons,which are present in specific
mRNAs,produced by genes on DNA of that cell.
• Non-Standard AminoAcids:
• These aminoacids donot take part in protein
synthesis but play important role in body.
• Examples are Citrulline,GABA,α-K-G,DOPA,etc.

4. Selenocysteine, the 21st L-α-Amino Acid
• Humans contain approximately two dozen selenoproteins that include certain
peroxidases and reductases, selenoprotein P, which circulates in the plasma, and
the iodothyronine deiodinases responsible for converting the prohormone
thyroxine (T4) to the thyroid hormone 3,3′5-triiodothyronine (T3).
• Peptidyl selenocysteine is not the product of a posttranslational modification,
but is inserted directly into a growing polypeptide during translation.
• However, unlike the other 20 protein amino acids, incorporation of
selenocysteine is specified by a large and complex genetic element for the
unusual tRNA called tRNASec which utilizes the UGA anticodon that normally
signals STOP. However, the protein synthetic apparatus can identify a
selenocysteine-specific UGA codon by the presence of an accompanying stem-
loop structure, the selenocysteine insertion element, in the untranslated region
of the mRNA.

6. CLASSIFICATION OF
STANDARD AMINOACIDS

7. I-BASED ON SIDE CHAIN STRUCTURE
• 1- side chain Polarity:
Non-Polar/Polar
• 2- Aliphatic/Branch chain/Aromatic side chain
…..………../Leu,Ile,Val/Tyr,Try,Phe
• 3- Sulphur containing side chains:
Cystein,Cystine,Metheonine
• 4- OH group containing side chain:
Tyrosine,Serine,T
• 5- Primary or Secondary Amino acid

8. II-BASED ON AMPHOTERIC PROPERTIES:
Cation/Zwitterion/Anion
III-BASED ON NUTRITIONAL REQUIREMENT:
Essential/Non-Essential
IV-BASED ON METABOLIC END PRODUCT:
Glucogenic/Ketogenic/both gluco&ketogenic
V-BASED ON ISOMERISM:
L and D Aminoacids

9. TYPES OF AMINO ACIDS BASED ON POLARITY
Amino acids are classified as
Nonpolar (hydrophobic) with
hydrocarbon side chains.
Polar (hydrophilic) with polar or
ionic side chains.
Acidic (hydrophilic) with acidic
side chains.
Basic (hydrophilic) with
–NH2 side chains.
Nonpolar Polar
Acidic Basic

10. Based on side chain polarity
• NON-POLAR
• These have even distribution of electrons.
• Amino acids with nonpolar side chains has a
nonpolar side chain that does not gain or lose
protons or participate in hydrogen or ionic bonds.
• The side chains of these amino acids can be thought
of as “oily” or lipid-like, a property that promotes
hydrophobic interactions
• The amino acids included in this group are
hydrophobic,e.g. Glycine, Alanine, Leucine,
Isoleucine, Valine and MethioninePhenylalanine,
Tryptophan and tyrosine

12. Amino Acids with Hydroxyl
Threonine
(α-amino b-y-propionic
hydroxy butyric)
Serine
(α-amino β-hydroxy
propanoic acid)
acid)

13. NON-POLAR -Amino Acids
• Aliphatic Amino acids:
• Glycine, Alanine, Valine, Leucine,
Isoleucine

14. Valine, Leucine, Isoleucine

15. Aromatic Amino Acids
Phenylalanine Tryptophan
Tyrosine

16. NON-POLAR-Location in proteins:
• In proteins found in aqueous solutions (a polar environment), the side
chains of the nonpolar amino acids tend to cluster together in the
interior of the protein, known as the hydrophobic effect, is the result
of the hydrophobicity of the nonpolar R groups, which act much like
droplets of oil that coalesce in an aqueous environment. By filling up
the interior of the folded protein, these nonpolar R groups help give
the protein its three dimensional shape.
• However, for proteins that are located in a hydrophobic environment,
such as a membrane, the nonpolar R groups are found on the outside
surface of the protein, interacting with the lipid environment.

19. NON-POLAR- Proline
Proline differs from other amino acids in that its side chain and α-
amino nitrogen form a rigid, five-membered ring structure. Proline,
then, has a secondary (rather than a primary) amino group. It is
frequently referred to as an “imino acid.”
The unique geometry of proline contributes to the formation of the
fibrous structure of collagen, but it interrupts the α-helices found in
globular proteins.

20. • POLAR
• These have uneven distribution of electrons such as acids and bases.
• polar non-charged
• polar charged-Acidic and Basic

21. UNCHARGED POLAR SIDE CHAINS
• These amino acids have zero net charge at physiologic pH (although
the side chains of cysteine and tyrosine can lose a proton at an
alkaline pH).
• They participate in hydrogen bonding of protein structure. The amino
acids in this group are- Proline, Serine, threonine, Cysteine,
Glutamine andAsparagine
• Serine, threonine, and tyrosine each contain a polar hydroxyl group
that can participate in hydrogen bond formation.
• The side chains of asparagine and glutamine each contain a carbonyl
group and an amide group, both of which can also participate in
hydrogen bonds.

23. Asparagine
(β-amide of aspartic
acid)
Glutamine
(y-amide of glutamic
acid)

26. UNCHARGED POLAR-Disulfide bond:
• The side chain of cysteine contains a sulfhydryl (thiol) group (−SH), which is
an important component of the active site of many enzymes. In proteins,
the –SH groups of two cysteines can be oxidized to form a covalent cross-
link called a disulfide bond (−S–S–). Two disulfide-linked cysteines are
referred to as cystine.
• Many extracellular proteins are stabilized by disulfide bonds. Albumin, a
blood protein that functions as a transporter for a variety of molecules, is
an example.
• Side chains as attachment sites for other compounds: The polar hydroxyl
group of serine, threonine, and (rarely) tyrosine can serve as a site of
attachment for structures such as a phosphate group. In addition, the
amide group of asparagine, as well as the hydroxyl group of serine or
threonine, can serve as a site of attachment for oligosaccharide chains in
Glycoproteins.

27. Disulfide bonds
-SH group of two Cys in proteins can be oxidized to form a
covalent disulfide bond.
 Disulfide bonds: play a special role in the structures of
many proteins by forming covalent links.
disulfide
bond

28. ACIDIC SIDE CHAINS
• The amino acids aspartic acid and glutamic acid are proton donors.
• At physiologic pH, the side chains of these amino acids are fully
ionized, containing a negatively charged carboxylate group (−COO−).
• The fully ionized forms are called aspartate and glutamate.

30. Acid Amino Acids
Aspartic Acid
(amino succinic acid)
Glutamic Acid
(α-amino glutaric acid)

31. Basic Amino Acids
These amino acids carry positive charge on the ‘R’ group and are dibasic
monocarboxylic acid. They are highly basic in nature.
The three aminoacid Lysine, Arginine and Histidine are included in thisgroup.

33. Basic Amino Acids
Lysine
(α-е-diamino caproic
acid)
Arginine
(α-amino d-guanido
valeric acid)

36. Amino Acids with Hydroxyl
Threonine
(α-amino b-y-propionic
hydroxy butyric)
Serine
(α-amino β-hydroxy
propanoic acid)
acid)

37. Sulfur-containing Amino Acids
Cysteine
(α-amino β-thio
propionic acid)
Methionine
(α-amino g-methyl
thiobutyric acid)

39. Secondary Amino Acid
is derived from primary aminoacids
• Proline (pyrrolidine
carboxylic acid)
derived from
glutamate

40. Based on Nutritional requirment

41. • non-essential amino
acids
-can be synthesized
by an organism
-usually are prepared
from precursors in 1-2
steps
• Essential amino acids
- cannot be made
endogenously
- must be supplied in
diet
eg. Leu, Phe…..
Nutritionally-Essential amino
acids :
Lysine, Leucine, Isoleucine,
Valine, Methionine,
Phenylalanine,
Threonine, Tryptophan
Nutritionally Nonessential
amino acids: Alanine,
glycine, aspartate ,
glutamate, serine, tyrosine,
cysteine, proline ,
glutamine, aspargine
N.B. Histidine & arginine are
semi essential. They are
essential only for infants
growth, but not for old
children or adults where in
adults histidine
requirement is obtained by
intestinal flora & arginine
by urea cycle

42. Essential a.a.--- PHLY VITH MAT
• 1-Ph---Phenylalanine
• 2-H---Histidine
• 3-Ly---Lysine
• 4-L---Lucine
• 5-V—Valine
• 6-I---Isolucine
• 7-Th—Threonine
• 8-M---Methionine
• 9-A---Arginine
• 10-T---Tryptophane

43. AMINO ACID CLASSIFICATION BASED ON
THEIR METABOLIC FATE
1. Glycogenic amino acids
2. Ketogenic amino acids
3. Glycogenic and Ketogenic amino acids

44. 1. GLYCOGENIC AMINO ACIDS
These amino acids serve as precursors for the formation of glucose and glycogen. The
amino acids included in this group are Alanine, Aspartate, Glycine,Methionine
2. KETOGENIC AMINO ACIDS
Fat can be synthezied from these amino acids. Two amino acids Leucine and Lysine are
exclusively ketogenic.

45. GLYCOGENIC AND KETOGENIC AMINO ACIDS
The four amino acids Isoleuciene, Phenylalanine, Tryptophan, Tyrosine are precursor for
synthesis of glucose as well as fat.

48. Secondary Amino Acid
is derived from primary aminoacids
• Proline (pyrrolidine
carboxylic acid)
derived from
glutamate

49. Based on Isomerism
• L-Aminoacids
• NH2 gp.present on left side of α-carbon,
• are found in humans.
• D-Aminoacids
• NH2 gp. present on right side of α-carbon,
are present in plants & bacteria

50.  The two enantiomers of each amino acid are
designated by D,L system according to the
D- and L-glyceraldehyde.
 D: Dextrorotation; L: Levorotation
•Only the L-amino acids have been found in proteins.
•(D-isomers have been found only in small peptides of bacteria cell
walls or in some peptide antibiotics).

51. Strerioisomers of Alanine
•
•
• L-alanine and its
enantiomer D-alanine
are shown here as
mirror images which
are not
superimposable.
All α-amino acids
except glycine contain
a assymmetric α-
carbon and thus have
D and L enatiomers.
Only L-enantiomer are
found in proteins.

52. Nonstandard amino acids
• Citrulline,Ornithine,Arginosuccinate—occur in liver urea cycle
• Β-Alanine—part of pantothenic acid
• γ-Amino-Butyric-Acid (GABA)—Neurotransmitter derived from
Glutamic acid,found in brain tissue.
• DihydroxyPhenylAlanine(DOPA)—metabolic product of phe n tyr.-
used to treat parkinsonism.
• Homocysteine—formed by demethylation of metheonine

53. Many additional nonstandard amino acids are
found in cells, but not in proteins
Ornithine and citrulline
Intermediates in amino acid metabolism.

54. •Amino acid derivatives
found in proteins
•4-Hydroxyproline and 5-
hydroxylysine in collagen.
•6-N-Methyllysine in myosin.
Nonstandard amino acids

55. Based on Amphoteric properties
• Cation
• Zwitterion
• Anion

56. Acid/base properties of AAs Amino acid has both a basic amine group and an acidic
carboxylic acid group.
 In neutral solution (pH 7.0), the amino acid contains a
negative charge and a positive charge. It is called a
zwitterion (German for “hybrid ion”).

58. •AAs ionize to various states depending on pH values.
• pI: there is a specific pH (designated isoelectric point, pI)
at which an AA has equal positive and negative charge (no
net electric charge) .
cation zwitterion anion
+H+ +H+
R—CH—COOH
|
NH +
R—CH—COO-
|
NH +
R—CH—COO-
|
NH
-H+ -H+
A+ A0 A-
3
pH<pI
3
pH=pI
2
pH>pI
Very important!!!

59. 9
At low pH, proton concentration [H+]is high.
Therefore, both amines and carboxylic acids
are protonated. (-NH + & -COOH)
3
At high pH, proton concentration is low.
Therefore, both amines and carboxylic acids
are deprotonated. (-NH2 & -COO-)
3At neutral pH, amines are protonated(-NH +) and
carboxylates are deprotonated(-COO-)

60. ACIDIC AND BASIC PROPERTIES OFAMINO
ACIDS
• Amino acids in aqueous solution contain weakly
acidic α-carboxyl groups and weakly basic α-amino
groups.
• Each of the acidic and basic amino acids contains an
ionizable group in its side chain.
• Thus, both free and some of the combined amino
acids in peptide linkages can act as buffers.
• The concentration of a weak acid (HA) and its
conjugate base(A-) is described by the Henderson-
Hasselbalch equation.

61. Derivation of the equation
• For the reaction HA A- +H+
[H+] [A-]
Ka = ───── ------ (1)
[HA]
• By solving for the [H+] in the above equation,
taking the logarithm of both sides of the equation,
multiplying both sides of+
the equation by -1, and
substituting pH = -log [H ] and pKa = -log [Ka]we
obtain:
[A-]
• pH = pKa + log ─── ------ (2)
[HA]
It is the (Henderson-Hasselbalch equation)

62. • Study the acid-base
properties of amino acids.
• Start the titration with the
amino acid in acidic form.
As we slowly increase the
pH we should be able to
plot a graph similar to the
one on the right.
mL NaOH
pH
1
2
3

63. Titrate our amino acid solution with NaOH to
see the pH curve as it relates to the amount of
NaOH added.
Use pH meters to monitor pH changes during
our titration.
Construct a graph of pH vs. Volume, mL of
NaOH added.

64. 2
0
4
6
14
12
10
8
0 2 4 8 10 12
pH
6
NaOH Volume,mL
pH vs. NaOH Volume, mL
X
Z
At point Z…?
At point X…?pKa = - log Ka
Ka = X-pKa
Henderson-
Hasselbalch [OH
]pH  pKa log
[H
]
HCl + NaOH NaCl + H2O

65. The titration curve points…
• 1 – where half of the original
acidic amino acid had been
titrated and became a
zwitterion.
• 2 - where the amino acid is
entirely in the zwitterion form.
• 3 – where half of the amino
acid is in the zwitterion form
and half is in the basic form.
1
2
3
Volume NaOH, mL
pH

66. What does each point mean?
• The pH of the midpoint of the
first leg (1) is the pK value of
the carboxylic acid group.
• The midpoint of the second leg
(2) is known as the isoelectric
point. All the amino acids are in
zwitterion form at this point.
• The pH of the midpoint of the
third leg (3) is equal to the pK of
3the –NH +
1
2
3
Volume NaOH, mL
pH

67. TITRATION CURVE OF ALANINE

68.  Note these structural features
1. All 20 are α-amino acids
2. For 19 of the 20, the  -amino group is primary; for
proline, it is secondary (imino acid)
3. Except glycine, the  -carbons for 19 of them are
asymmetric (or chiral).