Amino Acids, Peptides

and
Proteins
• Proteins are the most abundant biological
macromolecules, occurring in all cells and all
parts of cells

• All proteins are constructed from the same

ubiquitous set of 20 amino acids

• Cells can produce proteins with strikingly

different properties and activities by joining
the same 20 amino acids in many different
combinations and sequences
 Types of Proteins

Type Examples
• Structural tendons, cartilage, hair, nails
• Contractile muscles
• Transport hemoglobin
• Storage milk
• Hormonal insulin, growth hormone
• Enzyme catalyzes reactions in cells
• Protection immune response
3
 Amino Acids

• Building blocks of proteins

• Carboxylic acid group
• Amino group
• Side group R gives unique characteristics

R side chain
I
H2N—C —COOH
I
H
4
 Standard Amino Acids
• The 20 amino acids that are commonly found
in protein
• Knowledge of the chemical properties of the
common amino acids is central to an
understanding of biochemistry
• Grouped into 5 main classes based on the
properties of their R group, in particular, their
polarity or tendency to interact with water at
biological pH (near pH 7.0)
 Nonpolar, Aliphatic R Groups
• The R groups are nonpolar and hydrophobic
• The side chains of alanine, valine, leucine, and
isoleucine tend to cluster together within
proteins, stabilizing protein structure by
means of hydrophobic interactions
Nonpolar, Aliphatic R Groups
• Glycine has the simplest structure.
Its very small side chain makes no
real contribution to hydrophobic
interactions

• Methionine has a nonpolar thiother

group in its side chain

• Proline has an aliphatic side chain

with a distinctive cyclic structure.
 Aromatic R Groups
• Phenylalanine, tyrosine, and tryptophan, with
their aromatic side chains, are relatively
nonpolar (hydrophobic).
• All can participate in hydrophobic interactions
 Aromatic R Groups
• The hydroxyl group of tyrosine can form
hydrogen bonds, and it is an important
functional group in some enzymes
• Tyrosine and tryptophan are significantly more
polar than phenylalanine, because of the
tyrosine hydroxyl group and the nitrogen of
the tryptophan indole ring
 Polar, Uncharged R Group
• The R groups are more soluble in water or
more hydrophilic
• They contain functional groups that form
hydrogen bonds with water
• The polarity of serine and threonine is
contributed by their hydroxyl groups
 Polar, Uncharged R Group
• The polarity of cysteine is
contributed by its sulfhydryl group

• The polarity of asparagine and glutamine is

contributed by their amide groups
Positively Charged (Basic) R Groups
• The most hydrophilic R groups are those that
are either positively or negatively charged

• The amino acids in which the R groups have a

significant positive charge at pH 7 are lysine,
arginine and histidine
Positively Charged (Basic) R Groups
• Lysine has a second
primary amino group
at the ε position on
its aliphatic chain
Positively Charged (Basic) R Groups

• Arginine has a
positively charged
guanidino group
Positively Charged (Basic) R Groups
• Histidine has
imidazole group

• Histidine is the only

common amino acid
having an ionizable
side chain with a pKa
near neutrality
Negatively Charged (Acidic) R Groups

• The 2 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
•The pKa values and the isoelectronic point, pI, for the 20 a-amino acids.
•pKa1= a-carboxyl group, pKa2 = a-ammonium ion, and pKa3 = side chain
group.

Amino acid pKa1 pKa2 pKa3 pI

Glycine 2.34 9.60 --- 5.97
Alanine 2.34 9.69 --- 6.01
Valine 2.32 9.62 --- 5.97
Leucine 2.36 9.60 --- 5.98
Isoleucine 2.36 9.68 --- 6.02
Methionine 2.28 9.21 --- 5.74
Proline 1.99 10.96 --- 6.48
Phenylalanine 1.83 9.13 --- 5.48
Tryptophan 2.38 9.39 --- 5.89

pI or isoelectric pH – the pH at which a solute has no electric charge and thus does not
move in an electric field
 Amino acid pKa1 pKa2 pKa3 pI
Asparagine 2.02 8.80 --- 5.41
Glutamine 2.17 9.13 --- 5.65
Serine 2.21 9.15 --- 5.68
Threonine 2.11 9.62 --- 5.87
Tyrosine 2.20 9.11 10.07 5.66
Cysteine 1.96 10.28 8.18 5.07
Aspartic acid 1.88 9.60 3.65 2.77
Glutamic acid 2.19 9.67 4.25 3.22
Lysine 2.18 8.95 10.53 9.74
Arginine 2.17 9.04 12.48 10.76
Histidine 1.82 9.17 6.00 7.59
 Amino Acid Stereoisomers
Asymmetric or Chiral Carbon – a carbon atom
with four different substituents

-19 of the 20 standard amino acids are

asymmetric

- glycine is a symmetrical molecule because its

α-carbon is attached to 2 hydrogens
 Amino Acid Stereoisomers
Molecules with chiral carbons can exist as
stereoisomers (molecules that differ only in the
spatial arrangement of their toms)

Enantiomer
Stereoisomers are designated D (dextro-
rotatory) or L (levo-rotatory) according to the
direction in which the crystalline forms rotate
polarized light, to the right and left,
respectively.

Naturally-occurring proteins comprise

exclusively the L forms of amino acids.
 Amino acids as zwitterions

• An amino acid has both a basic amine group

and an acidic carboxylic acid group.
 Amino acids as zwitterions
• There is an internal transfer of a hydrogen ion
from the -COOH group to the -NH2 group to
leave an ion with both a negative charge and a
positive charge.
• This is called a zwitterion.

A zwitterion is a compound with

no overall electrical charge, but
which contains separate parts
which are positively and
negatively charged.
 Adding an alkali to an amino acid
solution
• If you increase the pH of a solution of an
amino acid by adding hydroxide ions, the
hydrogen ion is removed from the -NH3+
group.
 Adding an acid to an amino acid
solution
• If you decrease the pH by adding an acid to a
solution of an amino acid, the -COO- part of
the zwitterion picks up a hydrogen ion.
Peptides and Proteins
Peptide – 2 or more amino acids covalently joined by
peptide bond

Peptide bond – a substituted amide linkage between the

α-amino group of one amino acid and
the α-carboxyl group of another, with the
elimination of the elements of water
 Classification of Peptides
• Based on the number of amino acid units in
their chains
Dipeptide – amolecule containing 2 amino acids joined
by a peptide bond
Those containing 3-10 amino acids are called
tripeptides, tetrapeptides, pentapeptides, and so on
Oligopeptides – molecules containing more than ten,
but fewer than 20, amino acids
Polypeptide – a macromolecule containing 20 or more
amino acid units
• An amino acid unit in a peptide is often called a
residue (the part left over after losing a hydrogen
atom from its amino group and the hydroxyl
moiety from its carboxyl group)

• In peptide,
the amino acid residue at the end with a free
α-amino group is the amino-terminal (or N-
terminal) residue

the residue at the other end, which has a

free carboxyl group, is the carboxyl-terminal
(C-terminal) residue
Amino- Carboxyl-
terminal end terminal end
• The precise order of the amino acids in the
peptide is the amino acid sequence.
• Peptides are named according to their amino
acid sequence.
• By convention, the name is written so that the
higher priority carboxyl group is to the right
and the amino end to the left.
 Naming Peptides
• Name from the free amine (NH3+)
• Use -yl endings for the names of the amino acids
• The last amino acid with the free carboxyl group (COO-) uses its
amino acid name
serylglycyltyrosylalanylleucine

Ser-Gly-Tyr-Ala-Leu

SGYAL
 CH3
CH3 S
CH CH3 SH CH2
CH3 O CH2 O CH2 O CH2 O
-
H3N CH C N CH C N CH C N CH C O
H H H
 Protein
• A macromolecule composed of one or more polypeptides

• All 20 of the amino acids are necessary for protein

synthesis

• 10 amino acids not synthesized by the body

• arg, his, ile, leu, lys, met, phe, thr, trp, val

• Must obtain from the diet

• Of all the molecules encountered in living organisms,

proteins have the most diverse functions
 Functions of Protein
1. Catalysis
Enzymes are proteins that direct and accelerate
thousands of biochemical reactions in such processes
as digestion, energy capture, and biosynthesis
2. Structure
Some proteins provide protection and support.
Structural proteins often have very specialized
properties
ex. collagen, fibroin, elastin
 Functions of Protein
3. Movement
Proteins are involved in all cell movements
ex. actin, tubulin
4. Defense
A wide varieties of protein are protective
- keratin (skin cells) aids in protecting the organism
against mechanical and chemical injury
- fibrinogen and thrombin (blood clotting proteins)
prevent blood loss when blood vessels are damaged
- immunoglobulins (antibodies) are produced by
lymphocytes when foreign organisms such as bacteria
invade an organism
 Functions of Protein
5. Regulation
Binding a hormone molecule or a growth factor to
cognate receptors on its target cell changes cellular
function
Examples of peptide hormones include insulin and
glucagon, both of which regulate blood glucose levels

Growth hormones stimulates cell growth and division

Growth factors are polypeptides that control animal cell
division and differentiation
ex. platelet –derived growth factor (PDGF)
epidermal growth factor (EGF)
 Functions of Protein
6. Transport
Many proteins function as carriers of molecules and
ions across membranes and between cells
hemoglobin - carries oxygen to the tissues from the
lungs
lipoproteins (LDL and HDL) – transport lipids from the
liver and intestines to other organs
transferin and ceruloplasmin (serum proteins)that
transport iron and copper, respectively
 Functions of Protein
7. Storage
Certain proteins serve as a reservoir of essential
nutrients

ovalbumin (in bird eggs) and casein (in mammalian

milk) are rich sources of organic nitrogen during
development

zein (plant protein) perform a similar role in

germinating seed
 Functions of Protein
8. Stress response
The capacity of living organisms to survive a variety of
abiotic stresses is mediated by certain proteins

cytochrome P450 – a diverse group of enzymes found in

animals and plants that usually convert a variety of
toxic organic contaminants into less toxic derivatives

metallothionein – a cysteine-rich intracellular protein

found in virtually all mammalian cells that binds to and
sequesters toxic metals such as cadmium, mercury, and
silver
 Protein Classification
Based on Shape

• Fibrous proteins
- consist of polypeptide chains arranged side by side in long filaments
- insoluble in water and physically tough
- have structural and protective functions
• Globular proteins
- are coiled into compact, roughly spherical shapes
- usually water soluble
- have dynamic functions
- Most enzymes are globular proteins
Some Common Fibrous and Globular
Proteins
 Protein Classification
Based on Composition
• Simple proteins yield only amino acids on hydrolysis

• Conjugated proteins, which are much more common

than simple proteins, yield other compounds such as
carbohydrates, fats, or nucleic acids in addition to amino
acids on hydrolysis.
- consist of a simple protein combined with a nonprotein
component

The nonprotein component is called a prosthetic group

apoprotein – a protein without its prosthetic group

holoprotein – a protein molecule combined with its

prosthetic group

Conjugated protein are classified based on their prosthetic group

➢ glycoproteins – contain a carbohydrate component
➢ lipoproteins - contain lipid molecules
➢ metalloproteins – contain metal ions
➢ phosphoproteins - contain phosphate groups
➢ hemeproteins - possess heme groups
 Protein Structure
• The primary structure of a protein is simply
the amino acid sequence.

AGVGTVPMTAYGNDIQYYGQVT…
 Protein Structure
• The secondary structure of a protein describes how
segments of the peptide backbone orient into a
regular pattern.
– Regular patterns of hydrogen bonding in proteins
result in two patterns that emerge in nearly every
protein structure known: the a-helix and the
-sheet
– The location of direction of these periodic,
repeating structures is known as the secondary
structure of the protein
• α- helix is a rigid, rodlike structure that forms when a
polypeptide chain twists into a right-handed helical
conformation
- hydrogen bonds form between the N-H group of each
amino acid and the carbonyl group (C=O) of the amino
acid four residues away
• -there are 3.6 amino acid residues per turn of the helix
- amino acid R groups extend outward from the helix
α- helix
• β-pleated sheet form when
two or more polypeptide
chain segments line up side
by side
• Each individual segment is
referred to as β-strand
• Rather than being coiled,
each β-strand is fully
extended
• β-pleated sheets are
stabilized by hydrogen bonds
that form between the
polypeptide backbone N-H
and carbonyl groups of
adjacent chains
 Two β–pleated sheets
1. Parallel – the polypeptide
chains are
arranged in the
same direction

2. Antiparallel – run in
opposite direction
- more stable than
parallel β-sheets
because fully colinear
hydrogen bonds form
 Protein Structure
• The tertiary structure describes how the entire
protein molecule coils into an overall three-
dimensional shape.
• Secondary structure elements combine to form
tertiary structure
• Types of R group interaction:
hydrogen bond
disulfide bond (covalent bond)
hydrophobic interaction
electrostatic interaction
 Protein Structure
• The quaternary structure describes how different
protein molecules come together to yield large
aggregate structures

• Formed by noncovalent association of tertiary

structures
Protein Structure
Protein Structure
 Views of a protein
Wireframe Ball and stick
 Views of a protein
Spacefill Cartoon
 Loss of Protein Structure
Denaturation – the process of structure disruption
Denaturing conditions:
1. Strong acids or bases – result in protonation of some
protein side groups which alters hydrogen bonding and
salt bridge patterns (electrostatic interactions)
2. Organic solvents – interfere with hydrophobic
interactions
3. Detergents – disrupt hydrophobic interactions
4. Reducing agents – disrupts hydrogen bonds and
hydrophobic interactions
 Loss of Protein Structure
Denaturing conditions:
5. Salt concentration – the binding of salt ions to a protein’s
ionizable groups decreases interaction between
oppositely charged groups on the protein molecule
6. Heavy metal ions – may disrupt salt bridges and also
bond with sulfhydryl groups
7. Temperature changes – weak interactions (hydrogen
bond) are disrupted
8. Mechanical stress – stirring and grinding actions disrupt
the delicate balance of forces that maintain protein
structure