All proteins are composed of the same set of 20 amino acids that are linked together via peptide bonds. There are two main categories of amino acids - nonpolar amino acids that cluster in the interior of proteins, and polar amino acids that are charged or contain functional groups that allow hydrogen bonding. Key properties of amino acids include their ionization states, which depend on pH, and their ability to participate in covalent bonds like disulfide bridges that help determine protein structure. Amino acid sequences ultimately define the diverse functions that proteins perform in biological processes.

1. Amino Acids

2. Introduction to Proteins
• Proteins mediate nearly every process that takes place inside a cell.
• They are the most abundant biological macromolecules in cells.
• All proteins, regardless of organism, are composed of the same set of 20
amino acids that are incorporated into them during translation.
• Due to the nearly limitless variety in the sequences of amino acids in
proteins, nearly all imaginable functions can be encoded in proteins (Fig. 3-
1).
Luciferin Haemoglobin Keratin

3. Common Features of Amino Acids
• There are 20 "standard" amino acids.
• All amino acids contain an a carbon known as 
carbon is also termed as an chiral center to which
typically 4 different substituent groups are attached
(Fig. 3-2).
• These groups are:
1.amino group
2.carboxyl group,
3.hydrogen, and the
4.variable R group (side-chain).
• The a-amino and a-carboxyl groups are charged at
neutral pH.
• There are two possible configurations for these four
substituents--the "D" and "L" stereoisomers, which
are mirror images of each other (enantiomers) (Fig.
3-3).
• The standard amino acids have the L-configuration.

6. Numbering of Carbons in Amino Acids
The conventions for labeling the carbon atoms in amino acids is illustrated
using lysine in the figure. The  carbon is always carbon-2 of the amino
acid. The -carboxyl group is always carbon-1

7. Nonpolar, Aliphatic Amino Acids
• The amino acids in this group lack polar functional groups in their side chains.
• Due to the hydrophobicity of their R groups, they often cluster together within
the interior of proteins, stabilizing protein structure via hydrophobic
interactions.
Classification of Amino Acids by R Group
Amino acids are collected into different categories based on similarities in the
properties of their R groups. One such classification scheme relies heavily on the
polarity of the R groups.

8. Aromatic Amino Acids
• The side-chains of the aromatic amino acids, phenylalanine, tyrosine,
and tryptophan, overall are very hydrophobic.
• The R group of tyrosine also contains a polar hydroxyl group that can
participate in H bonding interactions.
• The R groups of tyrosine, and particularly tryptophan, absorb ultraviolet
light at a maximum of 280 nm wavelength (Fig. 3-6

9. Polar, Uncharged Amino Acids
• The R groups of the polar, uncharged
amino acids all contain polar functional
groups that can hydrogen bond with
water.
• Asparagine and glutamine are the amide
forms of the two negatively charged
amino acids aspartate and glutamate.
• The sulfhydryl group of the cysteine side
chain is a weak acid (pKa = 8.2). The
cysteine side chain therefore is mostly
uncharged at neutral pH.

10. Cysteine and Disulfide Bonds
• The thiol groups of two cysteine residues are readily oxidized to form a
covalently linked dimeric amino acid known as cystine.
• In cystine, the two cysteines are joined by a disulfide bond.
• The disulfide-linked cystine residue is strongly hydrophobic.
• In proteins, disulfide bonds form covalent links between different parts
of a polypeptide chain, or between two different polypeptide chains.

11. Positively Charged Amino Acids
• The most hydrophilic R groups are those that are either positively or
negatively charged.
• The side-chains of lysine and arginine are fully positively charged at
neutral pH.
• The histidine R group contains an aromatic imidazole group that is
partially positively charged at neutral pH.
• Histidine residues function in many enzyme-catalyzed reactions as proton
donors and/or acceptors.

12. Negatively Charged Amino Acids
The R groups of aspartate and glutamate contain carboxyl groups that are
fully negatively charged at neutral pH.

13. NON STANDARD AMINO ACIDS
Plant cell wall/
Collagen
Collagen
Mayosin
Prothrombin
Elastin
Ornithine and Citrulline are not found in
proteins, they are intermediate of urea cycle

14. • The -carboxyl and -amino groups of all amino acids, along with the
ionizable R groups of 7 amino acids, function as weak acids and bases in
aqueous solutions (Table 3-1).
• The pKa of these functional groups depend on the chemical properties of
the groups themselves and range between 1.8-2.4 for the -carboxyl
groups, and 8.8-11.0 for -amino groups.
Amino Acid Ionization

15. • The zwitterionic form predominates at neutral pH. The nonionic
form does not occur in significant amounts in aqueous solution at
any pH. A zwitterion can act as either an acid (proton donor) or a
base (proton acceptor).
• When a simple amino acid, is
dissolved in water at neutral pH, its
-carboxyl group is negatively
charged, and its -amino group is
positively charged. Such dipolar
ions (total charge equals 0) are
called zwitterions.
• Substances having this dual (acid-
base) nature are amphoteric and are
often called ampholytes
(amphoteric electrolytes).
Amino Acid Ionization

16. Titration of Simple Amino Acids
• The titration curves of simple amino acids such as
glycine, that have non-dissociable R groups, have
two stages,
1. the dissociation and titration of the -carboxyl
group (pK1, left) and
2. the -amino group (pK2, right). As shown above
the curve,
• the predominant ionic species in solution at low pH
is the fully protonated form, +H3N-CH2-COOH
(net charge = +1),
• In between the two plateaus, the zwitterionic form,
+H3N-CH2-COO- (net charge = 0) predominates.
• At the end of the titration, the fully dissociated
species H2N-CH2-COO- (net charge -1)
predominates. The curve shows that glycine has
two regions of buffering power centered ±1 pH
unit
Lastly, the pH at which the zwitterionic (0-charged) species of glycine
predominates is called the isoelectric point or isoelectric pH. The isoelectric pH
is exactly halfway between the two pKas for glycine.

17. Chemical Environment and the pKa
The pKa of the -carboxyl groups of all amino acids are lower than the pKa of
the carboxyl groups in methyl-substituted carboxylic acids such as acetic acid
(Fig. 3-11). This is due to the local chemical environment of the -carboxyl
groups in amino acids. Namely, placement near the -amino group, which is
positively charged, makes the -carboxyl groups of amino acids more acidic
than the carboxyl group of acetic acid. Similarly, the chemical environment
near -amino groups makes them more acidic than the amino groups of a
methyl-substituted amino compounds such as methylamine. In this case the
electron withdrawing properties of the oxygens on the -carboxyl groups of
amino acids make the -amino groups hold onto their protons less tightly than
in other environments.

18. Titration of Glutamate
The acidic amino acid, glutamate, has a second
carboxyl group present in its side-chain.
Thus the titration curve for glutamate (and
aspartate) has three stages,
1.the dissociation of a proton from carboxyl of
amino acid
2.the dissociation of a proton from carboxyl of
R chain
3.the dissociation of a proton from Amine of
amino acid
Based on inspection of the ionic forms in solution
(top) it is clear that the zwitterionic form of
glutamate occurs at a pH midway between that of
pK1 and pKR. Thus the pI for glutamate is 3.22.
The acidic amino acid, glutamate, has a second
carboxyl group present in its side-chain.
Thus the titration curve for glutamate (and
aspartate) has three stages,
1.the dissociation of a proton from carboxyl of
amino acid
2.the dissociation of a proton from carboxyl of
R chain
3.the dissociation of a proton from Amine of
amino acid
Based on inspection of the ionic forms in solution
(top) it is clear that the zwitterionic form of
glutamate occurs at a pH midway between that of
pK1 and pKR. Thus the pI for glutamate is 3.22.

19. Titration of Histidine
• Histidine has an imidazole R group that
contains a dissociable proton with a pKR of
6.0. Thus the titration curve for histidine
also has three stages:
1.the dissociation of a proton from
carboxyl of amino acid
2.the dissociation of a proton from Amine
of R chain
3.the dissociation of a proton from Amine
of amino acid
• For histidine, the 0-charged zwitterionic
species occurs in solution at a pH midway
between pKR and pK2 (pI = 7.59).
• Because the histidine pKR is near neutrality,
the R group of histidine plays a role in
buffering the pH of solutions containing
proteins.

20. Peptide Bonds
• Peptide bonds are amide linkages that join amino acids in oligopeptides,
polypeptides, and proteins.
• Peptide bonds are formed by condensation reactions in which the elements of
water are removed (dehydration) from the reacting -amino and -carboxyl
groups that come together to form the bond.
• The term oligopeptide refers to polymers with relatively few amino acid
residues.
• The term polypeptide signifies polymers of generally less than 10,000 mw,
whereas the term protein refers to longer polymers.

21. Structure of (Oligo)peptides
• The structure of the pentapeptide, serylglycyltyrosylalanylleucine (Ser-
Gly-Tyr-Ala-Leu, SGYAL).
• Aspartame (Artificial sweetner) is a tripeptide of Aspartic acid, phenyl
alanine, methyl ester.