Chemistry of amino acids- for Medical students

1. Chemistry of Amino acids
Dr. V.P.Acharya
Professor Biochemistry
IMS & SUM Hospital

2. Learning objectives
• Why study proteins?
• What do they do for us?
• What are they made of?
• Amino acids
• Classification of Amino acids
• Properties of AA
• Classification of proteins
• Properties of proteins
• Determination of protein structure
• Structural organisation of proteins
• Plasma proteins
• Immunoglobulins

3. Proteins- Proteios (Greek)
• Proteios = Primary or holding first
place
• The word protein that I propose to
you . . . I would wish to derive from
proteios, because it appears to be
the primitive or principal substance
of animal nutrition that plants
prepare for the herbivores, and
which the latter then furnish to the
carnivores.
• —J. J. Berzelius, letter to G. J.
Mulder, 1838

4. How will it be without proteins???

5. Proteins have been known since yore

6. Why study proteins?
• Proteins are very important biological molecules that play crucial
roles in virtually all biological processes
• 3/4th of total dry body weight- proteins
• Catalytic function:
Nearly all chemical reactions in biological systems are catalyzed by specific
enzymes.
• Transport and storage:
For example;
 Hemoglobin transports oxygen in erythrocytes
 Myoglobin carries & stores oxygen in muscle.
 Albumin transports free fatty acids in blood.
 Transferrin transports iron in blood.
• Coordinated motion: Actin and myosin are contractile proteins in muscle.

7. • Structural and Mechanical support:
e.g. collagen, a fibrous protein in skin and bone.
• Defense function:
e.g. Clotting factors prevent loss of blood.
Immunoglobulins protects against infections.
• Generation and transmission of nerve impulses:
e.g. Rhodopsin is the photoreceptor protein in retinal
rod cells.
• Control of growth and differentiation:
e.g. growth factor proteins.
hormones such as insulin and thyroid-stimulating
hormone.
• Genetic regulation:

8. Proteins are linear chains of amino
acids

9. Amino acids
• Building blocks of proteins
• Held by peptide bonds
• 300 amino acids in nature
• 20 AA make all the proteins (or is it 22?)-
human body
• All except Proline- α AA
• All AA have L-configuration (Exception: D-
serine & D-aspartic acid in brain)
• Genetic code specifies for 20 L-α- AA

10. All AA share a common structure
Amino group
Carboxyl
group
R varies in different AA

11. Naming of ‘C’ atoms
AA have a 3 letter abbreviation and 1 letter symbol

12. Classification of amino acids

13. A. Based on structure
I. Aliphatic AA (Gly, Ala, Val, Leu, Ile)
II. Hydroxy amino acids (Thr, Ser, Tyr)
III. Sulphur containing AA (Cys, Met)
IV. Dicarboxylic acid and their amides (Glu, Gln,
Asp, Asn)
V. Di amino acids/ Basic AA (Lys, Arg, His)
VI. Aromatic AA (Phe, Tyr, Trp)
VII. Imino acid/ heterocyclic AA (Pro)

14. I. Aliphatic AA

15. II. Hydroxy AA

16. III. Sulphur containing AA

17. IV. Dicarboxylic acid and their amides

18. V. Di-amino acids / Basic AA

19. VI. Aromatic AA

20. VII. Imino acid

21. B. Classification based on chemical nature
of amino acid in solution
1.Neutral AA
2. Acidic AA
3. Basic AA

22. 1. Neutral AA
• Neutral in solution
• Mono-amino Mono-carboxylic acid
• Gly, Ala, Val, Leu, Ile (GAVLI)
• Ser, Thr
• Phe, Tyr, Trp (PTT)
• Cys, Met
• Asn, Gln
• Pro

23. 2. Acidic AA
• Acidic in solution
• Monoamino dicarboxylic acid
• Aspartic acid (Asp) & Glutamic acid (Glu)

24. 3. Basic AA
• Basic in solution
• Diamino- monocarboxylic acids
• Lys, Arg & His

25. C. Classification based on polarity of side
chain
Amino
acid
Hydrophilic
(polar)
-vely charged (Asp, Glu)
+vely charged (Lys, Arg, His)
Uncharged (Ser, Thr, Asn,
Gln,Cys, gly, Tyr)
Hydrophobic
(non-polar)
Aliphatic side chain (Ala,
Val, Leu, Ile, Pro, met)
Aromatic AA (Phe, Trp)

26. D. Nutritional classification of AA
1. Nutritionally essential
2. Nutritionally non-essential
3. Nutritionally Semi-essential

27. 1. Nutritionally essential
I Love & Like To Take Potato Very Much
Ile, Leu, Lys Thr, Trp, Phe, Val, Met

28. 2. Nutritionally non-essential
Gly
Pro
Ser
Glu
Gln
Ala
Tyr
Cys
Asp
Asn

29. 3. Nutritionally semi-essential
• Arginine & Histidine
• Not synthesised in infants & children

30. D. Classification based on metabolism
1. Purely ketogenic- Leu
2. Ketogenic and glucogenic- Lys, Ile, Phe, Tyr &
Trp
3. Purely glucogenic- rest 14 AA

31. 21st century witnesses addition of 21st
AA
SELENOCYSTEINE
incorporated as such into proteins during
protein synthesis
Has separate codon- a stop codon (UGA)
Selenium present
Some enzymes e.g. Thioredoxin reductase
SeCys or SeC (U)

32. Now 22nd AA discovered
Oops!
Another AA
to memorize
!!!

33. Pyrrolysine- 22nd AA
• Pyl
• Methyl transferase enzyme of bacteria
• Coded by one of the stop codons

34. Derived AA
• After protein biosynthesis some AA are
modified- Hydroxyproline, hydroxylysine
• Some remain free- Citrulline, Ornithine,
Homocysteine
• Non-alpha AA- Gamma amino butyric acid
from Glu; β- alanine

35. Special groups of AA
Arg – Guanidium gr
Phe – Benzene ring
Tyr- phenol
Trp – indole
His- imidazolium
Pro- pyrrolidine

36. It is the darkest before dawn

37. PROPERTIES OF AMINO ACIDS

38. • All AA are soluble in water and alcohol
• Insoluble in non- polar solvents
• Gly, Ala, Val, Ser, Trp, His, Pro- sweet
• Leu- tasteless
• Ile, Arg- bitter
• High melting points > 2000c
• Colorless
• Crystalline
• MW- 77-205D
Physical properties

39. Optical properties
• Chiral centre
• Exception- Glycine
• Gly is optically
inactive

40. All natural AA are L-α- Amino acid
• Non- superimposible mirror
images- - Enantiomers (a
class of stereoisomers)
• D= Dextro; L= Laevo
• D- AA- some microbes,
certain antibiotics,
Gramicidin S, Polymyxin,
Antimycin
• Ile, Thr- 2 optically inactive
centres

41. Ampholytes and Iso -electric point
Due to ionizing property of AA, they
exert:
Amphoteric properties (zwitterion)
Acid base behaviour
Buffering activity

42. • AA can exist as ampholytes/ zwitterions
depending on the pH of the medium
• Ampho= both
• COO- anion
• NH3
+ - cation
• Acidic pH- ↑H+ -- overall charge becomes +ve
• Basic pH- ↓H+ -- overall charge on molecule
becomes negative
C
O
OH
R
NH3
C
O
O
R
NH3
C
O
O
R
NH2
LOW pH
Zwitterion
NEUTRAL
Carboxylate Form
HIGH pH
ammonium Form

43. Isoelectric pH (pI)
• pH at which there’s no net charge on the molecule
i.e. they cancel each other’s charge
• No mobility in the electrical field
• Solubility is minimum- precipitate
• Buffering capacity is minimum
• Each AA has a unique pI
• Helpful in separating AA in a mixture
• pI for Gly = 6.0
Asp = 3.0
Lys = 9.8
Arg = 10.8

44. pK???
• From pI point if acid (HCl) is added drop by drop, at
a point 50% cation + 50% zwitterion– pK1
• From pI if NaOH is added drop by drop, at one point
50% anion + 50% zwitterion– pK2
• pH = pK1 + pK2/ 2
• Gly pI = 2.34 + 9.6 / 2= 5.97
• > 2 ionizable groups- more pKs

45. • His- pK value of
imidazolium gr-
6.1
• Hence most
effective buffer
• Plasma proteins &
Hb have maxm
buffering capacity
due to His

48. General reactions of AA
A. Due to carboxyl gr
B. Due to amino gr
C. Due to side chains

49. Reactions due to carboxyl gr
1. Decarboxylation: alpha decarboxylation to
form corresponding amines
Histidine→ Histamine + CO2
Tyrosine → Tyramine + CO2
Tryptophan →Tryptamine + CO2
Lysine → Cadaverine + CO2
Glutamic acid → gamma amino butyric acid
(GABA) + CO2

50. 2. Amide formation: The extra COOH gr of
dicarboxylic acid can combine with NH3-
amide
Aspartic acid + NH3 → Asparagine
Glutamic acid + NH3 → Glutamine

51. Reactions due to Amino gr
3. Transamination: α amino gr is transferred to α keto
acid to form the form a new AA and α keto acid.

52. 4. Oxidative deamination: α amino gr removed
↓
Corresponding keto acid + ammonia
Glu- most common to undergo oxidative
deamination

53. 5. Formation of carbamino compounds: CO2
adds to the α Amino gr → Carbamino gr
• Helps in transport of oxygen
• Alkaline pH

54. Reactions due to side chains
6. Transmethylation: Methyl gr of Met gets
transferred after activation
Met + acceptor
↓
Methylated acceptor + Homocysteine

55. 7. Ester formation by the OH gr:
Hydroxy AA (Ser, Thr) form
phosphoproteins with phosphoric acid
With carbohydrates- glycoproteins

56. 8. Reactions of the amide gr:
Gln & Asn- form N-glycosidic bonds in
glycoproteins
9. Reactions of -SH gr:
2 Cys -- Cystine

57. Peptide bond formation
• 2 AA join covalently by substituted amide
linkage releasing a molecule of H2O
• CO-NH
• Covalent linkage

58. Colour reactions of AA
Reaction Answered by specific
group
Ninhydrin α amino group
Biuret Peptide bonds
Xanthoproteic Aromatic AA
Millon’s test Phenol (Tyr)
Aldehyde test Indole (Trp)
Sakaguchi’s test Guanidium (Arg)
Sulphur test Sulfhydryl (Cys)
Nitroprusside test Sulfhydryl (Cys)