AMINOACIDS & PROTEINS

1
Proteins, from the Greek proteios, meaning first, are a class
of organic compounds which are present in and vital to
every living cell. In the form of skin, hair, callus, cartilage,
muscles, tendons and ligaments, proteins hold together,
protect, and provide structure to the body of a multicelled
organism.

In the form of enzymes, hormones, antibodies, and

globulins, they catalyze, regulate, and protect the body
chemistry. In the form of hemoglobin, myoglobin and
various lipoproteins, they effect the transport of oxygen and
other substances within an organism.

Amino acids are the building blocks of proteins.

2
Interconversion pathways of nutrients in the body

3
 Amino Acids
• Amino acids contain two functional groups - an amine
group (NH2) and a carboxy group (COOH).

• Humans can synthesize only 10 of these 20 amino acids.

The remaining 10 are called essential amino acids because
they must be introduced in the diet (marked with “#” in the
following notes).
• The 20 amino acids that occur naturally in proteins differ in
the identity of the R group bonded to the  carbon. The R
group is called the side chain of the amino acid.
• The simplest amino acid, glycine, has R = H. When R is any
other group, the  carbon is a stereogenic center.
• The prefixes D and L are used to designate the configuration
at the stereogenic center of amino acids.
• Common naturally occurring amino acids are called L-amino
acids.
• According to R,S designations, all L-amino acids except
cysteine have the S configuration. 5
6
 Amino acids are classified according to the relative position
of the functional groups. The following table shows 3 simple
examples:

The 20 naturally occurring α-amino acids used by cells to

synthesise proteins can be generally represented by the
generic formula shown in the next slide.
The means the main difference between the various amino
acids lies in the structure of the "R" group. 7
8
The α-amino acids can be sub-classified according to how
the properties of other functional groups in the "R" group
influence the system:

Non-polar side chains (e.g. alkyl groups):

The hydrophobic effect = the aggregation of non-polar

systems in an aqueous environment.

The hydrophobic side chains are chemically unreactive and

tend to aggregate rather than be exposed to the aqueous
environment, so they tend to found on the interior of
proteins. Hydrophobic means "water hating" - remember "oil
and water don't mix" and "like dissolves like" - this is because
non-polar hydrocarbons do not interact with polar water
molecules in an energetically favourable way - they would
rather interact with another non-polar hydrocarbon molecule;
9
Polar side chains (e.g. amides, alcohols): These are side
chains can be involved in hydrogen bonding interactions.
Cysteine is important because of its ability to form
disulfide bonds.

Acidic side chains (e.g. carboxylic acids, phenols):

These carboxylate group will be -ve at physiological pH.
Often involved at the active sites of enzymes, in hydrogen
bonding interactions and in acid/base type reactivity.

Basic side chains (e.g. amines): Often involved at the

active sites of enzymes, in hydrogen bonding interactions
and in acid/base type reactivity (e.g. histidine)

10
Non-polar side
chains

11
 Polar side chains

Acidic side chains

Basic side chains 12

 Zwitterionic Structure of Aminoacids
• An amino acid is both an acid and a base.
• Amino acids are never uncharged neutral molecules.
They exist as salts, so they have very high melting
points and are very water soluble.
An amino acid can exist in three different forms
depending on pH.
Thus, alanine exists in three different forms depending on
the pH of the solution in which it is dissolved.
As the pH of a solution is gradually increased from 2 to 10,
the following process occurs:
 Form C

Form A

Form B

16
• Amino acids exist in different charged forms depending
on the pH of the aqueous solution in which they are
dissolved.
• For neutral amino acids, the overall charge is +1, 0, or
–1. Only at pH ~7 does the zwitterionic form exist.

How the charge of a neutral amino acid depends on the pH

17
• The –COOH and –NH3+ groups of an amino acid are
ionizable, because they can lose a proton in aqueous
solution. They have different pKa values. The pKa of the –
COOH group is typically ~2, whereas that of the –NH3+
group is ~9.

• Some amino acids such as aspartic acid and lysine, have

acidic or basic side chains. These additional ionizable
groups complicate the acid-base behavior of these amino
acids.

• Recall that the isoelectric point is the pH at which an amino

acid exists primarily in its neutral form. It can be calculated
from the average of the pKa values of the -COOH and -
NH3+ groups (for neutral amino acids only).
18
At intermediate pH's the zwitterion concentration increases,
and at the characteristic pH, called the isoelectric point (pI),
the negatively and positively charged molecular species are
present in equal concentration

•The isoelectronic point or isoionic point is the pH at which the

amino acid does not migrate in an electric field.

•This means it is the pH at which the amino acid is neutral, i.e.

the zwitterion form (neutral form) is dominant.
20
 Separations of Amino Acids
The differences in charge may be used to separate amino
acids (and peptides and proteins) by electrophoresis.
 Preparation of α-Amino Acids
1. Synthesis—SN2 Reaction of -Halo Acids with NH3

• Although the alkylation of ammonia with simple alkyl halides does

not generally afford high yields of 1°amines, this reaction using -
halo carboxylic acids does form the desired amino acids in high
yields.
• In this case, the amino group in the product is both less basic and
more sterically hindered than other 10 amines, so the single
alkylation occurs and the desired amino acid is obtained.

23
By modifying the nitrogen as a phthalimide salt, a single clean
substitution reaction of primary or secondary alkylhalides takes place.
This procedure (Gabriel synthesis) can be used in aminating
bromomalonic esters. Since the phthalimide substituted malonic ester
has an acidic H (colored orange), activated by the two ester groups,
this intermediate may be converted to a conjugated anion and further
alkylated, if needed. Finally, base catalyzed hydrolysis of the
phthalimide moiety and the esters, followed by acidification and
thermal decarboxylation, produces an amino acid

24
2. Alkylation of a Diethyl Malonate Derivative

• In the malonic ester synthesis, diethyl malonate is converted to a

carboxylic acid with a new alkyl group on its  carbon.

• This reaction can be adapted to the synthesis of -amino acids by

using commercially available diethyl acetamidomalonate.

25
HOMEWORK:

- Write the result of treatment of acetamidomalonate with

sodium ethoxide: the intermediate nucleophilic enolate that
then reacts with the alkyl halide.
• Note that the same acetamido malonate can be used to
form any primary α-amino acid.
• Hydrolysis of the malonate ester and the amide forms an
intermediate amino dicarboxylic acid that decarboxylates
to give the α-amino acid.

- Write the reaction of the resulted intermediate nucleophilic

enolate with:
• CH2O, followed by hydrolyses; What aminoacid results?
• Acrylonitrile, followed by hydrolyses; What aminoacid
results?
26
27
3. The Strecker Synthesis
• The Strecker synthesis converts an aldehyde into an amino acid
by a two-step sequence that adds one carbon atom to the
aldehyde carbonyl. Treating an aldehyde with NH4Cl and NaCN
first forms an -amino nitrile which can then be hydrolyzed in
aqueous acid to an amino acid.

28
• The mechanism for the formation of the -amino nitrile from an
aldehyde (the first step in the Strecker synthesis) consists of two
parts shown below.

29
Separation (Resolution) of Amino Acids

• The separation of a racemic mixture into its components is

called resolution. Thus, a racemic mixture is resolved into its
component enantiomers.
• Racemic mixtures can be resolved using the following general
strategy:

[1] Convert a pair of enantiomers that are unseparable due to

identical physical properties) into a pair of diastereomers

[2] Separate the diastereomers. Diastereomers may be

separated by crystallization, chromatography or other physical
manipulation, because they have different melting and boiling
points.

[3] Re-convert each separated diastereomer into the original

enantiomer 30
Separation of Amino Acids
Resolution of a racemic mixture
by converting it to a mixture
of diastereomers

31
Since amino acids are amphoteric, resolution could be achieved by
using either the acidic character of the COOH function, or the basic
character of the NH2 function. An enantiomerically pure Chiral
Base/Chiral Acid is used as the resolving agent.

Resolution with a Chiral Base

NH2 function is previously acylated, so that it will not compete
with the resolving base.

32
Resolution with a Chiral Acid

COOH function is first esterified, so that it will not compete with

the resolving acid.

33
Separation of Amino Acids—Kinetic Resolution
• Chiral reagents such as enzymes can be used to separate amino
acids based on the fact that two enantiomers react differently with
chiral reagents.

Enzyme:
Aminoacylase
from pig kidneys

34
Reactions of Amino Acids

• Amino acids contain two functional groups : amino and

carboxylic acid and thus they undergo the reactions characteristic
of those functional groups:

acylation (of NH2 group)

esterification (of COOH group)

These reactions are most important because they are utilised in

the formation of peptides and proteins.

• Another reaction, with ninhydrin, is used as a visual indicator as

there is a colour change (primary amines give a blue/purple
product)
• Biochemical reactions of aminoacids are the basis of nutrients
interconversions
35
Ninhydrin test

Amines (including α-amino acids) react with ninhydrin to give a

coloured product (test used for the visualisation of fingerprints).
The α-amino acids typically give a blue-purple product (the amino
acids are colorless).

A common application of the ninhydrin test is in

paper chromatography for visualisation of
spots where aminoacids have migrated. 36
Biochemical reactions
Transamination
as the name implies, refers to the transfer of an amine group from
one molecule to another. This reaction is catalyzed by a family of
enzymes called transaminases. Actually, the transamination
reaction results in the exchange of an amine group on one acid
with a ketone group on another acid.

H
- -
R1 C COO + R2 C COO
+
NH3 O

Transaminase

H
- -
R1 C COO + R2 C COO
+
O NH3
37
Decarboxylation

Is one of the reactions leading to amines (putrescine, cadaverine)

as a result of death of the living organisms.
Decarboxylation of histidine leads to histamine:

Histamine is a chemical mediator

(endogenous transmitter involved
in allergic manifestations, gastric
secretion), that exists in all the
tissues and mucous membranes
that represent the boundary of the
body in front of allergens.
38
Disulfide Bridges and Oxidation-Reduction:

The amino acid cysteine, as a thiol, undergoes oxidation and

reduction reactions involving the -SH (sulfhydryl group). The
oxidation of two sulfhydryl groups results in the formation of a
disulfide bond by the removal of two hydrogens and the dimer
aminoacid is sometimes listed as a distinct amino acid under the
name cystine.

The two peptide chains that constitute insulin are held together by
two disulfide links
In hair styling "permanent waving", disulfide bonds are first broken
39
and then created after the hair has been reshaped
1) Amino group: Acylation

is done either with acyl halides or anhydrides, to produce amido

group; Acylation with easy removable groups (BOC or Cbz) serves for
protection (temporary blocking) of the amino group during peptides
syntheses.

Only
illustrative

BOC

ensures an easy de-acylation later on, when the protection is no

longer needed: the rest attached to the amine will be eliminated as
CO2 and +C(CH3)3, precursor of isobutene, H2C=C(CH3)2 40
Acylation with easy removable groups (BOC or Cbz) serves for
protection (temporary blocking) of the amino group during peptides
syntheses. The Benzylchloroformate Cbz (obtained out of fosgene
and benzylic alcohol) is also used:

Cbz-Aminoacid

• After the Cbz-Aminoacid is used in the synthesis of peptide, the

protection group - abbreviated BOC in the case of di-t-
butyldicarbonate and Cbz in the case of benzylchloroformate - is
removed via hydrolysis (with CO2 evolvement)
• Benzyl protection groups can be removed also by hydrogenolysis
(with H2 in the presence of a Pd) 41
• Hydrogenolysis conditions are especially mild because they
avoid the use of either acid or base.
• Benzyl esters can also be removed with HBr in acetic acid.

42
2) Carboxylic Acid: Esterification

Esterification of the carboxylic acid is usually conducted under acidic

conditions.Under such conditions, amine functions are converted to their
ammonium salts and carboxyic acids are not dissociated. The first equation
is a typical Fischer esterification. The initial product is a stable ammonium
salt. The amino ester formed by neutralization of this salt is unstable, due to
the amino group that is acylated by the ester function.
.
illustrative

Benzylation (second equation) is preferred instead of CH3OH esterification,

because the benzyloxy fragment is easily removabile afterwards, as
C6H5CH2-Y, Y= H or OAc, i.e. toluene or benzylacetate
Also the esterification reaction is used during peptide synthesis,
this time for protecting the COOH group! The removal of the
protected group is achieved by the same methods, the C-
benzylated aminoacid is eliminated by either H2 /Pd catalyst or or
hydrolized in the presence of HBr & Acetic acid.

44
3) Carboxylic Acid: Amide formation- Peptide synthesis

The reaction of carboxylic group (of the first aminoacid) with the amino group
(of the second aminoacid, for example), to lead to an amide (in this case a
peptide) is performed only in the presence of dicyclohexylcarbodiimide
(DCC) that removes H2O (note that for a successful peptide synthesis, to
avoid undesired reactions of the second aminoacid with the amino group of
the first aminoacid, these two have to be protected as described above):

H
R1 COOH H2 N COOH R1 CO N COOH
Protected DCC Protected
NH 2 R2 NH 2 R2
Protected -DCUrea Protected

+HOH H H
N C N N C N

DCC O DCUrea
PEPTIDES AND PROTEINS

If the amine and carboxylic acid functional groups in amino acids

join together to form amide bonds, a chain of amino acid units,
called a peptide, is formed.

47
Peptides
• Amino acids joined together by amide bonds form larger
molecules than the peptides, called proteins (which are polymers
of more than 40 amino acids.).

48
Peptides

• To form a dipeptide, the amino group of one amino acid forms an

amide bond with the carboxy group of another amino acid. Since
each amino acid has both an amino group and a carboxy group,
two different peptides A, B, can be formed.

A.The COOH group of alanine can combine with the NH2 group of
cysteine.

49
Peptides
B. The COOH group of cysteine can combine with the NH2 group of
alanine.

50
• Note that, by convention, the N-terminal amino acid is always
written at the left end of the chain and the C-terminal amino
acid at the right.
• The peptide can be abbreviated by writing the one- or three-
letter symbols for the amino acids in the chain from the N-
terminal to the C-terminal end.

The conformational flexibility of peptide chains is limited

chiefly to rotations about the bonds leading to the alpha-
carbon atoms. This restriction is due to the rigid nature of the
amide (peptide) bond.

51
Automated Peptide Synthesis

• The previously described methods work well for the synthesis

of small peptides, but are very time consuming and
impractical for synthesizing larger proteins.

• The synthesis of larger peptides is accomplished using the

solid phase technique, that was originally developed by R.
Bruce Merrifield.

• In the Merrifield method, an amino acid is attached to an

insoluble polymer. Amino acids are sequentially added, one at
a time, thereby forming successive peptide bonds. Because
impurities and by-products are not attached to the polymer
chain, they are easily removed by washing with solvent at the
end of each stage of the synthesis.
52
Automated Peptide Synthesis

• A commonly used polymer is a polystyrene derivative that

contains –CH2Cl groups bonded to some of the benzene rings in
the polymer chain. The Cl atoms serve as handles that allow
attachment of amino acids to the chain.

53
Automated Peptide Synthesis
STEP 1
• An N-protected amino acid is attached to the polymer at its
carboxy group by an SN2 reaction.

• Once the first amino acid is bound to the polymer, the protection
group is removed, then another N-protected amino acid can be
added to react with the liberated NH2 group with the aid of DCC,
a.s.o., in a sequential repetition. In the very last step, HF cleaves
the polypeptide chain from the polymer. 54
 STEP 2 Removal of Protection group

STEP 3 Attach a new aminoacid (N-protected)

Steps 2 & 3
are repeated
as needed

LAST STEP In the very last step, HF cleaves the polypeptide chain
55
from the polymer.
Peptides
The carbonyl carbon of an amide is sp2 hybridized and has trigonal
planar geometry. Amides are more resonance stabilized than other
acyl compounds, so the resonance structure having the C=N
makes a significant contribution to the hybrid.

• A consequence of resonance stabilization is that all six atoms

involved in the peptide bond lie in the same plane.
• All bond angles are ~120° and the C=O and N—H bonds are
oriented 180° from each other.
• The peptide links being planar are resistant to conformational
56
change
Peptides
Resonance stabilization has important consequences.
Rotation about the C—N bond is restricted because it has
partial double bond character. As a result, there are two
possible conformations.

57
Peptides

• The structure of a tetrapeptide illustrates the results of

these effects in a long peptide chain.

58
 Peptides
• Due to steric hindrance, all peptide bonds are in trans configuration
• The 2 bonds around the α-carbon have freedom of rotation making
proteins flexible to bend and fold
• Relatively facile rotations may take place where the corners meet
(i.e. at the alpha-carbon). This aspect of peptide structure is an
important factor influencing the conformations adopted by proteins and
large peptides.

Interpeptide interactions, especially 59

Hydrogen bonds, lead to complex structures and folding patterns.
Proteins Structure
There are 4 levels of information concerning a protein structure

• Primary structure: reflected mainly by the contented aminoacids

and their sequence
• Secondary structure: reflected by the organization pattern in a-
helixes and b-pleats
• Tertiary structure: refers to the 3D complex folding of the regular
chain (a-helixes and b-pleats)
• Quarternary structure: refers to more complicated architecture,
resulted from association between polypeptides

60
Proteins — Primary Structure
Primary structure means the sequence of the amino acids in
the protein (amino acid sequence determines primary structure)

A change in one amino acid can alter the biochemical behavior of

the protein.
• Unique for each protein; innumerable possibilities
• Gene sequence determines aminoacids sequence (the proteins’
syntheses in the alive organisms is dictated by the DNA
• Each aminoacid is called a residue; numbering (& synthesis)
always from –NH2 end toward –COOH end

61
Proteins — Secondary Structure

Secondary structure is the initial folding pattern (periodic repeats)

of the linear polypeptide. Such folding regions arise due to
hydrogen bonding between the N—H proton of one amide and the
C=O oxygen of another.
• Two arrangements are particularly stable:
— the -helix and
— the -pleated sheet.

62
Proteins Secondary Structure- The a-helix

• The -helix forms when a peptide

chains twists into a right- handed
or clockwise spiral.
• Both myosin in muscle and -
keratin in hair are proteins
composed almost entirely of -
helices.
• α-helices can wind around each
other to form ‘coiled coils’ that are
extremely stable and found in
fibrous structural proteins such as
keratin, myosin (muscle fibers) etc

An alpha-helix
with hydrogen
bonds (yellow63
dotted)
Proteins Secondary Structure - The -pleated sheet
• Extended stretches of 5 or more aminoacids are called β-strands
• β-strands organized next to each other make β-sheets

• H-bonding pattern varies depending on type of sheet and usually

links two strands
• β-sheets are usually twisted rather than flat 64
Proteins—Secondary Structure

• If adjacent strands are oriented in the same direction (N-end to C-

end), it is a parallel β-sheet, if adjacent strands run opposite to each
other, it is an antiparallel β-sheet. There can also be mixed β-sheets

65
Proteins—Secondary Structure

66
Proteins—Secondary Structure
Four important features of the -helix are as follows:

[1] Each turn of the helix is 3.6 amino acids.

[2] The N—H and C=O bonds point along the axis of the helix. All
C=O bonds point in one direction, and all N—H bonds point in
the opposite direction.

[3] The C=O group of one amino acid is hydrogen bonded to an

N—H group four amino acid residues further along the chain.
Thus, hydrogen bonding occurs between two amino acids in
the same chain. The hydrogen bonds are parallel to the axis
of the helix.

[4] The R groups of the amino acids extend outward from the
core of the -helix. 67
Proteins—Secondary Structure

The -pleated sheet secondary structure forms when two

or more peptide chains, called strands, line up side by
side. All -pleated sheets have the following
characteristics:
[1] The C=O and N—H bonds lie in the plane of the sheet.
[2] Hydrogen bonding often occurs between the N—H and C=O
groups of nearby amino acid residues.
[3] The R groups are oriented above and below the plane of the
sheet, and alternate from one side to the other along a given
strand.
[4] The -pleated sheet arrangement most commonly occurs with
amino acids with small R groups, like alanine and glycine. With
larger R groups, steric interactions prevent the chains from
getting close together, and so the sheet cannot be stabilized by
68
hydrogen bonding.
Proteins — Secondary Structure

• Most proteins have regions of -helix and -pleated sheet, in

addition to other regions that cannot be characterized by either of
these arrangements.
• Shorthand symbols are often used to indicate regions of a protein
that have -helices and/or -pleated sheets. A flat helical ribbon
is used for the -helix, and a flat wide arrow is used for the -
pleated sheet.

69
Proteins—Secondary Structure
Spider dragline silk is a strong yet elastic protein because it has
regions of -pleated sheet and regions of -helix. The -helical
regions impart elasticity, and the -pleated sheet imparts strength.

Different regions of secondary

structure in spider silk 70
Proteins — Tertiary and Quaternary Structure
The three-dimensional shape adopted by the entire peptide chain
is called its tertiary structure.
Tertiary structure is the 3D folding or ‘bundling up’ of the
protein
There are 5 kinds of bonds that stabilize tertiary structure:

• H-bonds,
• van der Waals interactions,
• hydrophobic interactions,
• ionic interactions and
• disulphide linkages

Proteins generally fold

into conformations that
maximize stability.
Proteins — Tertiary and Quaternary Structure

[1] In the aqueous environment of the cell, this tendency generally

places most of the nonpolar side chains in the interior of the
protein, where van der Waals interactions between these
hydrophobic groups help stabilize the molecule. In this
arrangement, the greatest number of polar and charged groups
remain on the surface to maximize hydrogen bonding
interactions with water.

[2] Polar functional groups hydrogen bond with each other (not
just water), and amino acids with charged side chains like -
COO¯ and –NH3+ can stabilize tertiary structure by
electrostatic interactions.
Proteins — Tertiary and Quaternary Structure

[3] Disulfide bonds are the only covalent bonds that stabilize tertiary
structure. They are readily cleaved by reducing agents that supply
the protons to form the SH groups again

73
74
Proteins — Quaternary Structure

Quaternary Structure is the association of several

polypeptides
• The shape adopted when two or more folded polypeptide chains
aggregate into one protein complex is called a quaternary
structure of the protein.
• Each individual polypeptide chain is called a subunit of the
overall protein.
• Subunits (monomers) can be identical or different
• Disulfide bonds usually stabilize the oligomer
• Interpeptide interactions, especially hydrogen bonds, lead to
complex structures and folding patterns
• As an example, hemoglobin consists of two  and two  subunits
held together by intermolecular forces in a compact three-
dimensional shape. The unique function of hemoglobin is
possible only when all four subunits are together. 75
Hemoglobin

conjugated protein
because it is composed
of a protein unit and a
nonprotein molecule
called a prosthetic
group, the heme,
a complex organic
compound containing
Fe2+ ions (white
spheres) complexed
with a nitrogen
heterocycle called
porphyrin (red).

76
 Proteins — The Four Levels of Structure

The primary, secondary, tertiary, and quaternary structure of proteins

77
78
Protein structure determination

Around 90% of the protein structures available in the PROTEIN

DATA BANK have been determined by X-Ray Crystallography.
This method allows one to measure the 3D density distribution of
electrons in the protein (in the crystallized state) allowing thereby to
determine the 3D coordinates of all the atoms, which leads to a
certain resolution.
Roughly 9% of the known protein structures have been obtained by
NMR techniques.
The structure determination techniques are also useful when
working with very large protein complexes such as virus coat
proteins and amyloid fibers. A more qualitative picture of protein
structure is often obtained by Proteolysis (the breakdown of
proteins into smaller polypeptides or aminoacids. This generally
occurs by the hydrolysis of the peptide bond, and is most commonly
achieved by cellular enzymes called proteases. 79
 Denaturation of proteins
• Disruption of the normal structure of a protein, such that it loses
biological activity. Denaturing agents such as urea other salts, heat
or changes in pH, disrupt the 3D structure by changing the
interactions which maintain the 3D construction.
• Denaturation may be sometimes reversible. Removal of denaturant
agents is required for refolding
• Might also be irreversible. A cooked egg cannot be “uncooked.”

80
 Important Proteins
Proteins are generally classified according to their three-
dimensional shapes.

[1] Fibrous proteins are composed of long linear polypeptide

chains that are bundled together to form rods and sheets.
These proteins are insoluble in water and serve structural
roles, giving strength and protection to tissues and cells.

[2] Globular proteins are coiled into compact shapes with

hydrophilic outer surfaces that make them water soluble.
Enzymes and transport molecules are globular to make them
soluble in the blood and other aqueous environments.

81
 Important Proteins—-Keratins

• -Keratins are the proteins found in hair, hooves, nails, skin, and
wool.
• They are composed almost exclusively of long sections of -
helix units.
• They are very water insoluble.
• Two -keratin helices coil around each other, forming a structure
called a supercoil or superhelix. These in turn form larger and
larger bundles of fibers, ultimately forming a strand of hair.
• -Keratins also have a number of cysteine residues, and thus
disulfide bonds form between adjacent helices. The number of
disulfide bridges determines the strength of the material.
• Manipulation of -keratin disulfide bonds in hair can make curly
hair straight, or straight hair curly.

82
Important Proteins—-Keratins
Anatomy of a hair — It begins with α-keratin

83
Important Proteins—-Keratins
The chemistry of a “permanent” — Making straight hair curly

84
 Important Proteins—Collagen

• Collagen, the most abundant protein in

vertebrates, is found in connective tissues
such as bone, cartilage, tendons, teeth, and
blood vessels.

• Glycine and proline account for a large

fraction of its amino acid residues, whereas
cysteine is seldom.
• Because of the high proline content, it
cannot form a right-handed -helix. Instead,
it forms an elongated left-handed helix, and
then three of these helices wind around
each other to form a right-handed superhelix
or triple helix.
85
 Important Proteins—Collagen

Two different
representations
for the triple helix of
collagen

86
 Important Proteins—Blood Hemoglobin and Myoglobin
• Hemoglobin and myoglobin are globular proteins.
• They are called conjugated proteins because they
are composed of a protein unit and a nonprotein
molecule called a prosthetic group.

• The prosthetic group in both of these

proteins is heme, a complex organic
compound containing the Fe2+ ion
complexed with a nitrogen heterocycle
called porphyrin.
• The Fe2+ ion binds oxygen
Myoglobin stores oxygen in the
tissues, whereas
blood hemoglobin transports
oxygen to wherever it is needed. 87
 Important Proteins—Hemoglobin and Myoglobin

• Carbon monoxide is poisonous because it binds to the Fe2+ of

hemoglobin more strongly than does oxygen. Hemoglobin
complexed with CO cannot carry O2 from the lungs to the tissues.
Without O2 in the tissues for metabolism, cells cannot function, so
they die.
• The properties of all proteins depend on their three dimensional
shape, which depends on their primary structure. Sickle cell
hemoglobin is a mutant variation in which a single amino acid of
both  subunits is changed from glutamic acid to valine. This
changes the shape of hemoglobin, and has a profound effect on its
structure.
• Deoxygenated red blood cells with the sickle cell hemoglobin
become elongated and crescent shaped (sickle shaped). As a
result, they do not flow easily through capillaries, causing pain and
inflammation. They also break open easily, leading to severe
anemia and organ damage. 88
Important Proteins — Hemoglobin and Myoglobin

• The disease sickle cell anemia is found almost exclusively

among people originating from central and western Africa,
where malaria is an enormous health problem.
• Individuals who inherit the mutation responsible for sickle cell
anemia from both parents develop the disease. Those who
inherit it from only one parent do not develop the disease, but
are more resistant to malaria than individuals without the
mutation. This apparently accounts for this detrimental gene
being passed on from generation to generation.

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