Amino acids, Peptides &

Proteins
Introduction
• Proteins are the most abundant biological macromolecules
• Occur in great variety, different kind and size in a cell
• Exhibit enormous diversity of biological function (structure, catalysts
etc.)
• Constructed from the same set of 20 amino acids (alphabets in which
the language of protein is written)
• Examples: enzymes, hormones, antibodies, transporters, muscle
fibers, the lens protein of the eye, feathers, spider webs
Amino Acids
• Building blocks of proteins
• Proteins are polymers of amino acids, with each amino acid residue
joined to its neighbor by a specific type of covalent bond
• 20 different amino acids are commonly found in proteins
• Asparagine was the 1st amino acid discovered in 1806, Threonine was
the last one discovered in 1938
• All the amino acids have trivial or common names, Asparagine
isolated from asparagus, glutamate from wheat glutin, tyrosine from
cheese (tyros; cheese), glycine (sweet)
Structural features of amino acids
• All 20 of the common amino acids are α-amino acids
• They have a carboxyl group and an amino group bonded to the same
carbon atom (α carbon)
• They differ from each other in their side chains, or R groups
• R groups vary in structure, size, and electric charge, which influence
the solubility of the amino acids in water
• 3-letter abbreviation or 1-letter symbol have been assigned to the
amino acids which are used as shorthand for indicating the
composition of proteins
The additional carbons in an R group are commonly designated as beta,
gamma, delta, epsilon proceeding out from the alpha carbon
C1, 2, 3, 4, 5 and 6 starting from COO-
Continued.
• The carbon is bonded to four different groups: a carboxyl group, an
amino group, an R group, and a hydrogen atom in all except glycine
• The alpha carbon is thus a chiral center (an atom bound to 4 different
chemical spp. allowing for optical isomerism)
• Optical isomers are non-superimposable images
also called enantiomers
• Isomers: same chemical formula but distinct
structures, may have different properties
L and D forms of amino acids
• All naturally occurring biological molecules with
chiral atom occur in one form (L/D)
• The amino acids in proteins are L-sterioisomers
• D-Amino acid residues have been found only in
a few, generally small peptides, including some
peptides of bacterial cell walls and certain peptide
antibiotics
Classification of amino acids
• Based on the R-groups
• Grouped into five main classes particularly based on their polarity, or
tendency to interact with water at biological pH
• The polarity of the R groups varies widely, from nonpolar and
hydrophobic (water-insoluble) to highly polar and hydrophilic (water-
soluble)
Nonpolar, Aliphatic R Groups
• Aliphatic means straight chain
• R groups in this class of amino acids are nonpolar and hydrophobic
• These R groups stabilizes the protein structure by hydrophobic
interactions
• Glycine is the simplest, with small R group, little contribution towards
these interactions
• Proline has a distinctive cyclic structure
Aromatic R Groups
• Relatively non-polar
• All can participate in hydrophobic interactions
• Because of the OH group in Tyr and N in Trp ring, they show polarity
as compared to Phe
• Tyr and Trp absorbs UV light in 280 nm range, used for the
characterization of proteins by researchers
Polar, Uncharged R Groups
• More soluble in water, than nonpolar amino acids, because they
contain functional groups that form hydrogen bonds with water
• Serine and threonine are polar because of OH groups and Cys by SH
group
• Asparagine and glutamine by their amide groups
• Disulfide bonds between 2 Cys play important role in protein
structure
Positively Charged (Basic) R Groups
• The most hydrophilic R groups are those that are either positively or
negatively charged
• These have significant positive charge at neutral pH
• Lys has a second amino group
• In many enzyme-catalyzed reactions, a His residue facilitates the
reaction by serving as a proton donor/acceptor
Negatively Charged (Acidic) R Groups
• The two amino acids having R groups with a net negative charge at pH
7.0 are aspartate and glutamate,
• Each of which has a second carboxyl group
• At a pH superior to their pK, the carboxylic side chains lose a H+ ion
(proton) and are negative charged
Uncommon amino acids
• Uncommon amino acids mean the modification of common residues
already incorporated in the proteins
• E.g. 4-hydroxyproline a derivative of proline (found in plant cell wall
proteins and collagen)
• 5-hydroxylysine, derived from lysine (found in collagen)
• Other uncommon amino acids include 6-N-Methyllysine (in myosin),
alpha-carboxyglutamate (in prothrombin)
• Selenocysteine (contain selenium instead of sulfur in cysteine)
• Some of these are intermediate metabolites (ornithine)
Essential and Non-Essential amino acids
Amino Acids can act as acids or base
• When an amino acid is dissolved in water, it exists in solution as the
dipolar ion, or zwitterion (German for “hybrid ion”)
• It can either act as an acid (proton donor) or a base (proton acceptor)
• Substances having this dual nature are amphoteric and are often
called ampholytes (from “amphoteric electrolytes”)
Amino Acids Have Characteristic Titration
Curves
• Acid-base titration involves the gradual addition or removal of protons
• The plot has two distinct stages,
corresponding to deprotonation of two
different groups on glycine
• At very low pH, glycine is the fully protonated
form
• Midpoint: equimolar conc. of proton donor
and acceptor
• pK1 is for COOH
• pK2 is for NH3+
Titration curve of glycine
• It gives a quantitative measure of pKa of each of its ionizing group
(2.34 for the COOH group and 9.60 for the NH3 group)
• The titration curve of glycine has two regions of buffering power
Peptides and Proteins
• Polymers of amino acids are peptides and proteins
• Range in size from very small (Glutathione 3 a.a.) to very large (Titin
34,350 a.a.)
• Chain of amino acid is called peptide
• Two amino acid molecules can be covalently joined through a
substituted amide linkage, termed a peptide bond, to yield a
dipeptide (half life of peptide bond is about 7 years)
• Such a linkage is formed by removal of the elements of water
(dehydration) from the alpha carboxyl group of one amino acid and
the alpha amino group of another
Continued.
• Peptide bond formation is an example of a condensation reaction, a
common class of reactions in living cells
Continued.
• Tripeptide: 3 amino acids joined together by two peptide bonds
• Tetra-, Penta-, peptides: 4, 5 amino acids
• Oligopeptides 2-20 amino acid
• Polypeptide: more than 20 amino acids
• Protein & polypeptides are sometimes used interchangeably, the
former has mol wt. more than 10,000 and the latter has below 10,000
Range of sizes of biologically active peptides
• No generalizations about the molecular weights of biologically active
peptides and proteins in relation to their functions
• Range in length from two to many thousands of amino acid residues
• Consider the commercially synthesized dipeptide L-aspartyl-L-
phenylalanine methyl ester (aspartame or NutraSweet)
• Oxytocin (9 a.a.) stimulates uterine contractions
• Bradykinin (nine residues) inhibits
inflammation of tissues
Continued.
• Insulin (2 polypeptide chains, 51 amino acids, 30+21)
Multi-subunit proteins
• Proteins composed of 2 or more than 2 polypeptide chains associated
together non-covalently
• Individual polypeptide chain maybe identical or different
• Oligomeric: if at least 2 are identical, the identical units are called
protomers
• E.g. hemoglobin has 4 subunits 2 alpha, and 2 beta, all held together
by non-covalent interactions
• Some proteins have their subunits linked covalently e.g. insulin units
are linked by disulfide bonds (individual chains are not considered
subunit then, referred to as chain commonly)
Some Proteins Contain Chemical Groups
Other Than Amino Acids
• Some proteins contain only amino acids, no other chemical
constituents e.g. chymortypsinogen, ribonuclease A etc.
• Some have permanently associated chemical components in addition
to amino acids, these proteins are referred to as conjugated proteins
• The non-amino acid part of these proteins is called prosthetic group
• Nature of prosthetic group is used to classify them into different
groups e.g. lipoproteins, metalloproteins, glycoproteins etc.
• Some may contain more than one prosthetic groups
• Prosthetic group has a specific role in the function of protein