Amino acids are organic compounds that contain amino and carboxyl groups. There are 20 amino acids that make up proteins. Proteins have a primary structure defined by the sequence of amino acids. The amino acids fold into secondary structures like alpha helices and beta sheets held together by hydrogen bonds. Tertiary structure is formed by interactions between amino acid side chains. Quaternary structure involves interactions between multiple polypeptide chains. Denaturation disrupts secondary and tertiary structures, causing a loss of biological activity.

1. Amino Acids and Proteins

2. Amino acids
• Amino acids are a group of organic compounds containing two functional
groups— amino and carboxyl
• The amino acids are termed as α-amino acids, if both the carboxyl and amino
groups are attached to the same carbon atom
• The amino group (—NH2) is basic while the carboxyl group (—COOH) is acidic
in nature.

3. Amino acids
• There are about 300 amino acids occurring in nature but only
20 of them occur In proteins.
• The 20 amino acids are different in the R group.
• The amino acids (except glycine) possess optical isomerism.
• Contain asymmetric carbon atom (attached to four different groups)
• The amino acids of the proteins are L-α-amino acids (α-amino
group is on the left side configuration).

4. Amino acids…
• One of the 20 amino acids called proline is not an amino acid.
• It is an imino acid as It contains imino group (-NH).

5. Amino acids…
• At physiological pH (approximately pH=7 .4) the carboxyl group is
dissociated forming a negatively charged carboxylate ion (-COO-) and
the amino group is protonated, forming positively charged ion (-NH3
+)

6. Abbreviations and symbols of amino acids

7. Classification of amino acids
A. Amino acid classification based on the structure
A. Nutritional classification of amino acids
A. Amino acid classification based on their metabolic fate

8. A. Amino acid classification based on the structure
• Amino acids are classified according to the side chain:
a. Nonpolar, Aliphatic R Groups
b. Aromatic R Groups
c. Polar, Uncharged R Groups
d. Positively Charged (Basic) R Groups
e. Negatively Charged (Acidic) R Groups

9. A. Amino acid classification based on the structure

10. B. Nutritional classification of amino acids
• Based on the nutritional requirements, amino acids are grouped into
two classes:
1. Essential or indispensable amino acids:
• Cannot be synthesized by the body and need to be supplied through the diet
• These are 10 amino acids: Arginine, Valine, Histidine, Isoleucine, Leucine, Lysine,
Methionine, Phenylalanine, Threonine, Tryptophan.(A.V. HILL, MP., T. T.)
• arginine and histidine are semi-essential amino acids
2. Non-essential or dispensable amino acids:
• The body can synthesize and need not be consumed in the diet
• These are 10 amino acids: glycine, alanine, serine, cysteine, aspartate, asparagine,
glutamate, glutamine, tyrosine and proline

11. C. Amino acid classification based on their
metabolic fate
• From metabolic view point, amino acids (carbon skeleton of amino
acids) are divided into three groups
1. Glycogenic amino acids
• These amino acids can serve as precursors for the formation of glucose or glycogen.
• Example: alanine, aspartate, glycine, methionine etc
2. Ketogenic amino acids
• Fat can be synthesized from these amino acids.
• Two amino acids leucine and lysine are exclusively ketogenic.
3. Glycogenic and ketogenic amino acids
• The four amino acids isoleucine, phenylalanine, tryptophan, tyrosine are precursors for
synthesis of glucose as well as fat

12. Proteins
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13. Proteins
• Are polymers of amino acids
• Amino acids are monomers of proteins
• Are polypeptides of >50 -1000 amino acids
• Are folded in a way that they have a biological activity
• Every protein has
• a unique sequence of amino acid residues,
• a very specific shape from which its biologic function is derived
• a characteristic size
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14. STRUCTURE OF PROTEINS…
• The term protein is generally used for a polypeptide containing more
than 50 amino acids.
• Some authors use ‘polypeptide’ even if the number of amino acids is
a few hundreds.
• They prefer to use protein to an assembly of polypeptide chains with
quaternary structure

15. STRUCTURE OF PROTEINS…
• Each protein has a unique sequence of amino acids which is
determined by the genes contained in DNA.
• The amino acid composition of a protein determines its physical and
chemical properties
• The amino acids are held together in a protein by covalent peptide
bonds or linkages
• It is when the amino group of an amino acid combines with the carboxyl
group of another amino acid
• Conventionally, the peptide chains are written with the free amino
end (N-terminal residue) at the left, and the free carboxyl end (C-
terminal residue) at the right

16. STRUCTURE OF PROTEINS…
Formation of a peptide bond.
Use of symbols in representing a peptide

17. Classification of proteins
• Classification is based on shape and physical characteristics
• Two major classes:
1) Globular proteins and
2) Fibrous proteins
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18. Classification…
Globular protein Fibrous protein
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20. Classification based on functions
• Enzymes
• Transport proteins e.g transferrin, Hb, ceruloplasmin
• Nutrient and storage proteins e.g. ovalbumin
• Contractile and mobility proteins - actin & myosin of skeletal muscle
• Structural proteins e.g. Collagen
• Defense proteins: Ig, fibrinogen and thrombin
• Regulatory proteins: hormones, repressors
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21. Protein structure
• Proteins differ from each other: each has a distinctive:
• Amino acid (aa) sequence
• aa composition,
• and a unique 3D structure
• The 3D structure of a protein is called the native conformation
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22. Protein structure…
• Some proteins have a single polypeptide chain e.g. ribonuclease,
serum albumin, cytochrome C
• Oligomeric proteins have 2 or more chains
• Polypeptides with similar aa sequence and functions are said to be
homologous
• Such polypeptides have a common ancestral sequence
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23. Levels of Protein structure
• Follows a certain hierarchy
• Four organizational hierarchies:
• Primary (10) structure
Is the order (or sequence) of amino acid residues
• 20 structure
the development of regular patterns of hydrogen bonding, which
result in distinct folding patterns
• 30 structure
the 3D structure resulting from further regular folding of the
polypeptide chains
• 40 structure
Two or more polypeptide chains linked together
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24. STRUCTURE OF PROTEINS

25. Primary structure
Is the linear structure.
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26. Secondary structure
• The way the chains of amino acids fold or turn upon themselves
• Held together by hydrogen bonds between non-adjacent amine (N-H)
and carboxylic (C-O) groups
• May form an alpha helix, a beta-pleated sheet or a random coil
• Secondary structure provides a level of structural stability (due to H-
bond formation)
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27. Secondary structure
• Most common regular 20 structure are the α helix and β sheet.
• The α-helix model was postulated by Linus Pauling in 1951
• The α-helix is a coiled structure stabilized by hydrogen bonding.
• H-bonding occurs between N-H group of one amino acid and the C=O
group of the fourth amino acid in the chain (n+4).
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28. Alpha helix
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29. Alpha helix
• The most regular and the most predictable from sequence
• It’s helical along the axis
• Each amino acid residue corresponds to a 100° turn in the helix (i.e.,
the helix has 3.6 amino acid residues per turn
• The pitch of the alpha-helix (the vertical distance between one
consecutive turn of the helix) is 5.4 Å (0.54 nm)
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30. Amino acid propensities to form α-helix
• Different amino-acid sequences have different propensities
for forming α-helical structure
• AA with high helix propensity are met, ala, leu, glu, lys
• Pro and gly have poor helix-forming propensities.
• Pro forms a kink in the helix, because it cannot donate an amide
H-bond and also its side chain interferes sterically with the
backbone of the preceding turn - inside a helix
• This forces a bend of about 30° in the helix axis.
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31. Beta pleated sheet
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32. Beta (β) pleated sheet
• It is almost extended (linear)
• Has polypeptides arranged side by side (stacked one over
another) to form sheets of molecules
• The polypeptide is a zigzag rather than a helical structure; the
strand has typically 3-10 aa
• Anti parallel β-pleated sheet: Adjacent polypeptide run in
opposite direction
• Parallel β-pleated sheet run in the same direction
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33. β pleated sheet
• Is stabilized by inter-chain H bonds
• The side chains protrude from the zigzag structure
• In the fully extended β strand, successive side chains point
straight up, then straight down, then straight up, etc.
NB: Antiparallel arrangement produces the strongest inter-
strand stability because it allows the inter-strand hydrogen
bonds between carbonyls and amines to be planar, which is their
preferred orientation
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34. Beta turns
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35. Tertiary structure
• Caused by interactions between R groups;
• They including:
1. H-bonds
2. disulphide bridges
3. ionic bonds
4. hydrophilic / hydrophobic interactions (Van der Waals)
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36. Tertiary structure
• In globular proteins the tertiary structure or macromolecular
shape determines the biological properties
• A protein composed of a single polypeptide molecule, 30
structure is the highest level of structure that is attained
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37. Factors that influence 30 structure
1. Hydrophobic AA residues are in the interior, away from water
2. Residues with hydrophilic R groups are on the exterior so that they
make interactions with water molecules
3. Disulfide bond stabilizes the structure (covalent bond)
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38. Quaternary…
• The interaction between multiple polypeptides as aggregates or
prosthetic groups that results in a single, larger, biologically active protein
• A protein containing a prosthetic group is called a conjugated protein
• Quaternary structure may be held together by Van der Waals and
electrostatic forces (not covalent bonds)
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39. Quaternary
• Haemoglobin is tetrameric.
• Has four heme units
• Two identical α and β globin
chains.
• The α and β chains are very
similar but distinguishable in
both primary structure and
folding
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40. Levels of protein structure
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41. Denaturation
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42. Denaturation
• Involves the disruption and destruction of both the 20 and 30 structures
of proteins
• Denaturation reactions are not strong enough to break the peptide
bonds
• the 10 structure remains the same after a denaturation process.
• Disrupts the normal alpha-helix and beta sheets in a protein and uncoils
it into a random shape.
• The protein loses its biological activity.
• Denaturation may be reversible or irreversible
• Reversible denaturation: Removal of denaturing agent results in refolding of the
protein (renaturation)
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43. Denaturing agents
• A variety of reagents and conditions can cause denaturation:
 Heat disrupt H bonds and non-polar hydrophobic interactions.
 It increases the kinetic energy and causes the molecules to vibrate leading to
disruption of the bonds.
 E.g. Cooking denatures proteins to make it easier for enzymes to
digest them
 medical supplies and instruments are sterilized by heating to denature
proteins in bacteria and thus destroy the bacteria.
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44. Denaturing agent
• Alcohol disrupts H bonding.
• A 70% alcohol solution is used as skin disinfectant.
• This conc. is able to penetrate the bacterial cell wall and denature the proteins and enzymes
inside of the cell
• Acids and bases disrupt salt bridges held together by ionic charges.
• Salt bridges result from the neutralization of an acid and amine on side chains
• A double replacement reaction occurs: positive and negative ions in the salt
change with the positive and negative ions in the new acid or base added.
• E.g. in the digestive system, acidic gastric juices cause the curdling (coagulating) of milk.
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45. Denaturing agents…
• Heavy metal salts e.g. Hg+2, Pb+2, Ag+1, Cd+2 etc disrupt salt bridges in
proteins in the same way as acids
• The reaction of a heavy metal salt with a protein usually leads to an
insoluble metal protein salt.
• A reverse reaction is used in acute heavy metal poisoning.
• A person who may have swallowed a significant quantity of a heavy metal salt
is given a protein such as milk or egg whites to precipitate the poisonous salt.
• Then an emetic (substance that induces vomiting) is given so that the
precipitated metal protein is discharged from the body.
• Heavy metal salts disrupt disulfide bonds because of their high affinity
and attraction for sulfur
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46. Denaturing agent…
• Salt concentration: salting-out
 When a large amount of salt is added to a protein solution, the salt ions
compete with the protein atoms for water molecules
 Solvation spheres around the protein molecules are removed.
 The protein molecules aggregate and precipitate out (salting-out)
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47. Structure-function relationship of proteins
• For water soluble proteins, non-polar amino acids are found in the
center of the protein (stabilising structure) while polar amino acids are
found on the surface (capable of interacting with water molecules)
• For membrane-bound proteins, non-polar amino acids tend to be
localised on the surface in contact with the membrane, while polar
amino acids line interior pores (to create hydrophilic channels)
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48. Structure-function relationship…
• For enzymes, the active site specifically depends on the location and
distribution of polar and non-polar amino acids as hydrophobic and
hydrophilic interactions can play a role in substrate binding to the
active site
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49. Structure-function relationship…
• The non-covalent forces shape the structure of a proteins
• Globular proteins e.g. Hb & Mb. Both are heme proteins
 Mb is a single polypeptide folded into 8 stretches of α-helices. The heme
group is in a crevice in the protein
 Interior of the molecule has non polar aa, the charged aa are on the surface
of the molecule
 Hb has 4 polypeptide chains, each with a heme group.
 They facilitate transport of O2
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50. Biologically Important Peptides
• The term ‘peptide’ is used when the number of constituent amino
acids is less than 10
• Some examples of biologically active peptides and their functions are
described here.
1. Glutathione:
• It is a tripeptide composed of 3 amino acids (γ- glutamyl-cysteinyl-glycine)
• It is widely distributed in nature and exists in reduced or oxidized states.
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51. Biologically Important Peptides
• Functions of Glutathione
• Serves as a coenzyme for certain enzymes e.g. prostaglandin PGE2
synthetase, glyoxylase.
• It prevents the oxidation of sulfhydryl ( SH) groups of several proteins to
disulfide ( -S-S- ) groups
• Performs specialized functions in erythrocytes
• It maintains RBC membrane structure and integrity.
• It protects hemoglobin from getting oxidized by agents such as H2O2.
• Glutathione is involved in the detoxication process.
• Toxic amounts of peroxides and free radicals scavanged by glutathione
peroxidase
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52. Biologically Important Peptides
2. Oxytocin :
• It is a hormone secreted by posterior pituitary gland and contains 9 amino
acids (nonapeptide).
• Oxytocin causes contraction of uterus.
3. Vasopressin (antidiuretic hormone, ADH) :
• ADH is a nonapeptide produced by posterior pituitary gland.
• It stimulates kidneys to retain water and thus increases the blood pressure.
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