Amino acid chemistry Protein chemistry Amino acid & Protein structure, organisation, properties and classification for MBBS, BDS, MSc, BSc, BPT, Nursing Youtube: https://youtu.be/CP_PL21mqOc

1. CHEMISTRY OF AMINO ACIDS
Dr Anurag Yadav
Assistant professor,
Department of Biochemistry

3.  Molecules made from amine (-NH2)
and carboxylic acid (-COOH)
functional group along with a side
chain specific to each amino acid.
 Carbon , hydrogen, oxygen, and
nitrogen.

4. Abbreviations and Codes
11) Leucine L, Leu
12) Lysine K, Lys
13) Methionine M, Met
14) Phenylalanine F, Phe
15) Proline P, Pro
16) Serine S, Ser
17) Threonine T, Thr
18) Tryptophan W, Trp
19) Tyrosine Y, Tyr
20) Valine V, Val
1) Alanine A, Ala
2) Arginine R, Arg
3) Asparagine N, Asn
4) Aspartic acid D,
Asp
5) Cysteine C, Cys
6) Glutamine Q, Gln
7) Glutamic Acid E, Glu
8) Glycine G, Gly
9) Histidine H, His
10) Isoleucine I, Ile

5. CLASSIFICATION OF AMINO
ACIDS
 Based on structure
 Based on side chain
 Based on metabolism
 Based on nutritional requirement

6.  Based on structure
MONOAMINO
MONOCARBOXYLIC
FOUND IN PROTEINS
NOT FOUND IN PROTEINS
DI BASIC MONO
CARBOXYLIC
MONO AMINO DI
CARBOXYLIC
NON α
DERIVED
IMINO ACID
HETEROCYCLIC
AROMATIC
ALIPHATIC

7. ALIPHATIC
MONOAMINO MONO
CARBOXYLIC
•Simple aa- Glycine, Alanine
•Branched chain aa- Leucine,
Isoleucine, Valine
•Hydroxy aa- Serine,
Threonine
•Sulphur containing aa-
Cysteine, Methionine
•Amino acids with amide
group- Aspargine, Glutamine

8. MONO AMINO DI
CARBOXYLIC
Aspartic
acid
Glutamic
acid
H3N C COO–
H
CH2
COO–
H3N C COO–
H
CH2
CH2
COO–
Glutamic
Acid
Aspartic
Acid
Di basic mono
carboxylic
Lysine,
Arginine

9. Aromatic
Phe,
Tyr
Heterocyclic Trp,
His
Imino acid Proline

10. FOUND IN PROTEINS
NOT FOUND IN
PROTEINS
NON α
DERIVED
Hydroxyproline,
Hydroxylysine
Citruline,
Ornithine,
Homocysteine
GABA

11.  Based on structure
MONOAMINO
MONOCARBOXYLI
C
FOUND IN PROTEINS
NOT FOUND IN
PROTEINS
DI BASIC MONO
CARBOXYLIC
MONO AMINO DI
CARBOXYLIC
NON α
DERIVED
IMINO ACID
HETEROCYCLIC
AROMATIC
ALIPHATIC
Aspartic acid,
Glutamic acid
Lysine,
Arginine
Tryptophan,
Histidine
Phenylalanin
e, Tyrosine
Proline
Hydroxyproline,
Hydroxylysine
Citruline,
Ornithine,
Homocysteine
GABA

12.  BASED ON SIDE CHAIN
POLAR SIDE
CHAINS
NON POLAR
SIDE CHAINS
Ala, Val,Leu,
Ile,Met, Pro, Phe,
Trp
Ser, Thr, Asn,
Gly, Cys, Gln
Acidic- Asp, Glu
Basic- Lys, Arg,
His

13.  BASED ON METABOLISM
KETOGENIC &
GLUCOGENIC
PUERLY GLUOGENIC
PURELY
KETOGENIC
Leucin
e
Remaining
14
Lys, Ile,
Phe, Tyr,
Trp

14.  BASED ON NUTRITIONAL
REQUIREMENT
NON ESENTIAL
PARTIALLY
ESSENTIAL
ESSENTIAL
Remaining
10
Arg, His
Ile, Leu, Thr, Lys,
Met, Phe, Trp, Val

15.  PROPERTIES OF AMINO ACIDS
◦ Physical properties
◦ Optical properties
◦ Ampholyte & isoelectric point
◦ Chemical properties

16.  Physical properties
◦ Colourless, crystalline, soluble in water &
alcohol (polar solvent) insoluble in
nonpolar solvent (Benzene), have high
melting point (>200o)

17.  Optical properties (d & l forms)
◦ L amino acid
◦ D amino acid

18.  Ampholyte & isoelectric point
◦ Due to ionizing property of aa they exert
 Amphoteric property and
 Buffering activity

19.  Amino acids exists as ampholyte or
zwitterions

20. Isoelectric pH
 The pH at which the molecule carries
equal no. of positive and negative
charges i.e there is no net charge

21. Transamination
 The alpha amino group of amino acid
can be transferred to alpha keto acid
to form the corresponding new amino
acid and alpha keto acid
 Important for the interconversion of
amino acids and for synthesis of
non-essential amino acids

23. Deamination
 The alpha amino group is removed
from the amino acid to form the
corresponding keto acid and ammonia
 Glutamic acid is the most common
amino acid to undergo oxidative
deamination

24. PEPTIDE BOND
 Alpha carboxyl group of one amino acid
reacts with alpha amino group of another
amino acid to form
a peptide bond or CO-NH bridge

26. Characteristic of a peptide bond
 Partial double bond.
 C-N bond is ‘trans’ – no freedom of
rotation because of partial double
bond character.
 Distance is 1.32A.
 Side chain are free to rotate on either
side of peptide bond.
 The angle of rotation is known as
Ramchandran angles.

28.  IMPORTANCE OF AMINO ACIDS
◦ Formation of proteins
◦ Formation of glucose
◦ Enzyme activity
◦ Transport & storage of ammonia
◦ As a buffer
◦ Detoxification reactions

29. Proteins

30.  CLASSIFICATION OF PROTEINS
◦ Based on function
◦ Based on composition & solubility
◦ Based on shape
◦ Based on nutritional value

31. Based on function
Catalytic proteins - enzymes
Structural proteins - Collagen, Elastin, Keratin
Contractile proteins – Myosin, Actin
Transport proteins – Hb, Albumin, Transferrine, Lipoproteins
Storage - Myoglobin, Apoferritin
Regulatory proteins/ Hormones – ACTH, Insulin, Growth
hormone
Genetic proteins – Histones
Protective proteins – Immunoglobulin, interferones, Clotting
factors

32. Based on composition and
solubility
Simple –
• Albumin
• Globulin
• Protamine
• Prolamine (Zein, Gliadin, Hordein)
• Lectin
• Scleroprotein (Collagen, Keratin)

33. Conjugated –
• Glycoproteins (Blood gr Ag) >10%
carbohydrate Mucoprotein
• Lipoproteins, (HDL, LDL, VLDL)
• Nucleoproteins (Histones)
• Chromoproteins (Hb, Flavoproteins)
• Phosphoproteins (Casein, Vitellin)
• Metalloproteins (Hb, Cytochrome,
Tyrosinase, carbonic anhydrase)
Derived – Peptones, Peptides

34. Based on shape
• Globular – Albumin, Globulin, Protamines,
Troponins
• Fibrous – Collagen, Elastin, Keratins
Based on nutritional value
• Nutritionally rich proteins (Complete
proteins/ first class proteins) – Casein
• Incomplete proteins – Pulses;Methionine,
Cereals;Lysine
• Poor proteins – Zein;Tryptophan & Lysine

35. The structure can be divided into four levels of
organization.
1. primary structure.
2. secondary structure.
3. tertiary structure.
4. quaternary structure.

36. Bonds responsible for
protein structure
• peptide bonds
• disulphide bonds
Covalent
bonds
• Hydrogen bond
• Hydrophobic interactions
• Ionic bond
• Van der waals interactions
Non
covalent
bonds

37.  Covalent bonds: is by
sharing the electrons btwn
atoms.
 Ionic Bond: electrostatic
attraction btwn two ionized
groups of opposite
charges. Formed by
transfer of electrons.

38.  Hydrogen bond: sharing of
hydrogen btwn electron
donors
 Hydrophobic interactions:
non-polar groups have
tendency to associate with
each other in an aqueous
medium, is referred to as

40.  Van Der Waals forces: very weak
forces of attractions between all
atoms due to oscillating dipoles. It
is short range of attractive forces
btwn chemical groups in contact.
 They occur in both polar and non-
polar molecules.
 Although weak, collectively
contribute for maximum towards
the stability of protein structure.

43. Primary structure
 Sequence of the amino acids in a
polypeptide chain.
 Maintained by peptide bonds.
 One or more covalent disulfide bonds
may also be involved in the primary
structure

44.  One should have a clear concept of
term sequence:
◦ Gly-Ala-Val
◦ Gly-Val-Ala
 Stabilized by:
◦ Peptide bond
◦ Di-sulfide bonds

45.  Ex- Insulin
Gastrin
Glucagon
Oxytocin
stomatostatin

47. Insulin
 Is a polypeptide hormone produce by
β-cells of langerhans of pancreas.
 It has profound influence on metabolism
of Carbohydrates, fat & proteins.
 It is considered as the anabolic hormone.

48.  It was the first hormone to be isolated,
purified & synthesized.
 First hormone to be sequenced
 First hormone to be produced by
recombinant DNA technology.

49. Structure
 Human Insulin contain 51 aminoacids,
arranged in TWO Polypeptide chains.
 Chain A = 21 AA
 Chain B = 30 AA
 Two Interchain Disulfide bridge = A7-
B7 & A20-B19.
 Intrachain Disulfide link in chain A = 6-
11.

53. Synthesis
 Gene for protein synthesis
is located on Chr 11
 Produced from β-cell of
Langerhans of pancreas.
 Synthesis involve two
precursors
◦ Preproinsulin = 108AA
◦ Proinsulin = 86 AA

54. Dept Of Biochemistry, FMMC

55.  These are sequentially degraded to form the
active hormone Insulin and Connecting
peptide (C-Peptide)
 C-peptide has no biological activity, however
its estimation in plasma serves as the useful
index for endogenous production of insulin.
 In β-cells, Insulin combines with Zinc to form a
complex & stored in granules.

56. Primary structure determines
Biological activity
 Protein with specific primary structure
will automatically forms its natural
three dimensional shape.
 Higher level of organisation is
dependent on primary structure.
 Even single AA change (mutation) in
linear chain cause profound effect.
◦ Eg: HbS- Sickle cell anemia (Hb-A-6th-
Glu-to-Val)

57. Secondary structure
 The folding of short (3 to 30 residue),
segments of polypeptide into geometrically
ordered units.
 The secondary structure denotes the
configurational relationship b/w residues
which are about 3-4 aa apart in the linear
sequence
 Secondary structure is stabilized by non-
covalent bonds

58. • Hydrogen Bond
• Electrostatic bond /
Ionic Bonds
• Hydrophobic bonds -
helps to hold lipophilic
side chains together.
• Van der Waals forces
Bonds
stabilising
secondary
structure
of protein

59. 1. a helix
2. b pleated sheet

61. Alpha helix
 Most common & stable
 It is a spiral structure. Rt handed
 The polypeptide bonds form the backbone
 The side chains extend outwards
 The structure is stabilized by the hydrogen bonds
 The hydrogen bonds are parallel to the axis of the
helix.
 A complete turn of the helix contains an average of
3.6 amino acid residues

63. Ex
Fibrous protein
-alpha keratin, myosin, tropomyosin, fibrin
Globular protein
- hemoglobin, myoglobin
 Hb has approx 80% a helical str
 Proteins such as digestive enzymes
chymotrypsine are virtually devoid of a helix

64. β sheet
 Pleated pattern in which the R groups
of adjacent residues point in opposite
directions.
 The peptide backbone of the beta sheet
is highly extended.

65.  Composed of 2 or more polypeptide
 Beta sheets derive stability from
hydrogen bonds between the carbonyl
oxygens and amide hydrogens of
peptide bonds.

66.  Bonds are formed with adjacent
segments of beta sheets.
 The hydrogen bonds are
perpendicular to the polypeptide
backbone (parallel in a-helix)

67.  Beta bends are formed by abrupt u-turn
folding of chain, with intrachain Di-
sulfide bridges stabilizing these bonds.
 b-sheet conformation can occur in two
ways
-Parallel pleated sheets
-Anti parallel pleated sheets

69. The b structure can occur between separate peptide
chains eg silk fibroin.
Can occur between segments of same peptide chain
where it folds on itself eg lysozyme

70. Superhelix
 Three stranded helix. The resultant three
stranded rope is twisted into a superhelix
 It is left handed helix of 3 residues per turn
 Stabilized by interchain hydrogen bonds,
lysinonorleucine bonds
 This structure gives the tensile strength
 Eg collagen

71. Tertiary structure
 Refers to the three dimensional conformation
of a polypeptide.
 The secondary str is folded & twisted about
itself forming the 3 dimensional arrangement
of the polypeptide chain
 Amino acid that are very distant from each
other are brought very near due to the folding

72.  It is maintained by Ionic bonds, hydrogen bonds,
hydrophobic, disulphide bonds, vander waals
forces
 It is a compact molecule with hydrophobic side
chains held interior while the hydrophillic groups
are on the surface of the protein molecule.
 Ex- Myoglobin.
 Assisted by chaperons

74. Motifs:
Protein

75.  Motifs are superstructures, with alpha
and beta chains arranged in proteins.
◦ Beta hairpin
◦ Helix-loop-helix
◦ Zinc finger
◦ Helix-turn-helix

77.  Domain: term used to denote
compact globular functional units of a
protein.
 It is relatively independent region of
protein.

78. Turns

79. Quaternary structure
 The arrangement of the polypeptide subunits
in three dimensional complexes.
 It exists in proteins consisting of two or more
identical or different polypeptide chains
 Bonds –hydrogen bond, ionic bonds,
hydrophobic interactions.
 Each polypeptide chain is termed as subunit
or monomer

80. Ex-
 2 a chain & 2 b chain of Hb
 2 heavy chains & 2 light chains of Ig
 Creatine kinase is a dimer
 Lactate dehydrogenase is a tetramer
 Aspartate transcarbomylase has 6
subunits

84. Properties of proteins
Physical properties
◦ Colloidal in nature- exert osmotic
pressure
◦ Molecular weight
◦ Shape
◦ Isoelectric pH

85.  Precipitation reactions
◦ Salting out (ammonium sulphate, sodium
sulphate)
◦ Isoelectric pH
◦ Organic solvents (Alcohol)
◦ Heavy metal ions (Cu, Zn, Hg, Cd)
◦ Alkaloidal reagents (Phosphotungstic
acid, TCA, Picric acid, Sulphosalicylic
acid, Tanic acid)

86. Denaturation: The phenomenon of
disorganization of native protein structure is
known as denaturation.
 Denaturation results in the loss of secondary,
tertiary and quaternary structure of proteins.
 This involves a change in physical, chemical
and biological properties of protein molecules.

87.  Agents of denaturation Physical agents : Heat ,
violent shaking, X-rays, UV radiation.
 Chemical agents : Acids , alkalies, organic solvents
(ether, alcohol), salts of heavy metals (Pb, Hg),
urea, salicylate, detergents (e.g. sodium dodecyl
sulfate).

88. Characteristics of
denaturation
1. The native helical structure of protein is lost
2. The primary structure of a protein with peptide linkages
remains intact
3. The protein loses its biological activity
4. Denatured protein becomes insoluble in the solvent in
which it was originally soluble.
5 The viscosity of denatured protein (solution) increases
while its surface tension decreases.
6.Denatured protein is more easily digested. This is due to
increased exposure of peptide bonds to enzymes.
7. Denaturation is usually irreversible .
8 Careful denaturation is sometimes reversible (known as
renaturation ). Hemoglobin undergoes denaturation in the
presence of salicylate.
9. Denatured protein cannot be crystallized

89. Coagulation :
 The term ‘coagulum’ refers to a semi-solid
viscous precipitate of protein. Irreversible
denaturation results in coagulation.
 Heat coagulation test is commonly used to
detect the presence of albumin in urine.
 Flocculation : It is the process of protein
precipitation at isoelectric pH. Usually
reversible

90. Biological important peptides:
 Glutathione : tri-peptide.
 Glutathione serves as a coenzyme for certain
enzymes e.g. prostaglandin PGE2 synthetase,
glyoxylase.
 It maintains RBC membrane structure and
integrity.
 involved in the transport of amino acids.
 involved in the detoxication process.

91.  Thyrotropin releasing hormone ( TRH ) : It is a
tripeptide secreted by hypothalamus. TRH
stimulates pituitary gland to release thyrotropic
hormone.
 Oxytocin : It is a hormone secreted by posterior
pituitary gland and contains 9 amino acids
(nonapeptide). Oxytocin causes contraction of
uterus

92.  Vasopressin: ADH is also a nonapeptide
produced by posterior pituitary gland. It
stimulates kidneys to retain water and thus
increases the blood pressure.
 Angiotensins: stimulates the release of
aldosterone from adrenal gland.
 Aspartame : 200 times sweeter than sucrose
,

93.  Peptide antibiotics : Antibiotics such as
gramicidin , bacitracin , tyrocidin and
actinomycin.
 Gastrointestinal hormones : Gastrin,
secretin etc. are the gastrointestinal
peptides which serve as hormones.

94. Amino acids useful as drugs
 D-Penicillamine
 N-Acetylcysteine is used in cystic fibrosis,
and chronic renal insufficiency, as it can
function as an antioxidant.
 Gabapentin is used as an anticonvulsant