Proteins

Proteins

 They are needed for the synthesis of enzymes, certain

hormones & some blood components; for the
maintenance and repair of existing tissues; for the
synthesis of new tissue; sometimes for energy.
 Characteristics of proteins
 Most abundant substances in nearly all cells –
they account for about 15% of a cell’s overall
mass & for almost half of a cell’s dry mass. They
also contain the elements C,H,O,N & sometimes
S. Hemoglobin, the oxygen-transporting protein of
blood, contains iron.
 A protein is a naturally occurring, unbranched
polymer in which the monomer units are amino
acids.
 Amino acids: the building blocks for
proteins
 Amino acid is an organic compound that contains both an
amino (-NH2) group and a carboxyl (-COOH) group. An α-
amino acid is an amino acid in which the amino group and the
carboxyl group are attached to the α-carbon atom. The general
structural formula for an α—amino acid is
 Amino acids: the building blocks for
proteins
 The word protein comes from the Greek proteios which
means “of first importance”.
 The R group present in an α-amino acid is called the amino
acid side chain. Side chains vary in size, shape, charge,
acidity, functional groups present, hydrogen-bonding ability
and chemical reactivity.
 Amino acids: the building blocks for
proteins
• A nonpolar amino acid is an
amino acid that contains one
amino group, one carboxyl
group, and a nonpolar side
chain.
• Tryptophan is a borderline
member of this group because
water can weakly interact
through hydrogen bonding with
the NH ring location on
tryptophan’s side-chain ring
structure.
 Amino acids: the building blocks for
proteins

• A polar neutral amino acid is

an amino acid that contains
one amino group, one
carboxyl group, and a side
chain that is polar but neutral.
There are 6 polar neutral
amino acid; serine, cysteine,
threonine, asparagine,
glutamine & tyrosine.
 Amino acids: the building blocks for
proteins
• A polar acidic amino acid is an amino acid that contains one
amino group and two carboxyl groups, the second carboxyl group
part of the side chain. There are two polar acidic amino acids;
aspartic acid and glutamic acid.
• A polar basic amino acid is an amino acid that contains two
amino groups and one carboxyl group, the second amino group
being part of the side chain. There are three polar basic amino
acids: lysine, arginine and histidine.
 Chirality and amino acids

• Because only L amino acids are constituents of proteins, the

enantiomer designation of L or D will be omitted in subsequent
amino acid & protein discussions. With few exceptions, the aa
found in nature and in proteins are L isomers. For aa, the L isomer
is the preferred form, whereas for monosaccharides the D isomer
is preferred.
 Rules for drawing Fischer projection formulas for aa structures:
1. the –COOH group is put at the top of the projection, the R group at
the bottom. This positions the carbon chain vertically.
 Chirality and amino acids
2. The –NH2 group is in a horizontally position. Positioning it on the
left denotes the L isomer, and positioning it on the right denotes the
D isomer.
Acid-base properties of amino acids
 In pure form, aa are white crystalline solids
with relatively high decomposition points.
Also, most aa are not very soluble in water
because of strong intermolecular forces
within their crystal structures.
 Zwitterion, from the German term meaning
“double ion”, is a molecule that has a
positive charge on one atom and a negative
charge on another atom, but which has no
net charge.
 ISOELECTRIC POINTS AND
ELECTROPHORESIS
 The amounts of the various forms of an aa – zwitterion, negative
ions and positive ions – that are present in an aqueous solution of
the aa vary with solution pH. There is no pH at which ionic aa
forms are absent, but there is a pH at which there is an equal
number of positive and negative charges present, which produces
a “no net charge” situation. The “no net charge” pH value for an aa
solution is called its isolectric point.
 Isoelectric point is the pH at which an aa solution has no net
charge because an equal number of positive and negative charges
are present.
 ISOELECTRIC POINTS AND
ELECTROPHORESIS
 Mixtures of aa in solution can
be separated by using their
different migration patterns at
various pH values.
 Electrophoresis is the
process of separating charged
molecules on the basis of their
migration toward charged
electrodes associated with an
electric field.
 peptides
 Peptide is an unbranched chain of aa, each joined to the next by
a peptide bond. A compound containing two aa is specifically
called a dipeptide; three aa joined together in a chain constitute a
tripeptide. The name oligopeptide is loosely used to refer to
peptides with 10 to 20 aa residues, and the name polypeptide is
used to refer to longer peptides.
 A polypeptide is a long unbranched chain of aa, each joined to
the next by a peptide bond.
 Biochemically important small peptides
SMALL PEPTIDE HORMONES
oThe two best-known peptide
hormones, both produced by the
pituitary gland, are oxytocin &
vasopressin.
oOxytocin plays a role in
stimulating the flow of milk in a
nursing mother.
oOxytocin regulates uterine
contractions and lactation.
Vasopressin regulates the
excretion of water by the
kidneys; it also affects blood
pressure.
 SMALL PEPTIDE neurotransmitters
o Enkephalins are pentapeptide neurotransmitters produced by the
brain itself that bind at receptor sites in the brain to reduce pain.
o the pain-reducing effects of its action play a role in the “high”
reported by long-distance runners, in the competitive athlete’s
managing to finish the game despite being injured, and in the
pain-relieving effects of acupuncture.
 SMALL PEPTIDE antioxidants
o The tripeptide gluthathione is present in
significant concentrations in most cells and is
considerable physiological importance as a
regulator of oxidation-reduction reactions.
o It functions as an antioxidant, protecting cellular
contents from oxidizing agents such as peroxides
and superoxides.
 General structural characteristics of proteins

 A protein is a peptide in which at least 40 aa residues are present.

These are the second type of biochemical polymer.
 A monomeric protein is a protein in which only one peptide chain
is present. Large proteins, those with many aa residues, usually
are multimeric. A multimeric protein is a protein in which more
than one peptide chain is present. The peptide chains present in
multimeric proteins are called protein subunits.
 General structural characteristics of
proteins
 Proteins, on the basis of chemical composition, are classified as simple or
complex. A simple protein is a protein in which only aa residues are present.
A conjugated protein is a protein that has one or more non-aa components,
which may be organic or inorganic, are called prosthetic groups. It is a
non-aa group present in a conjugated protein.
 Conjugated proteins may be further classified according to the nature of the
prosthetic groups present. Lipoproteins contain lipid prosthetic groups,
glycoproteins contain carbohydrate groups, metaloproteins contain a specific
metal.
 Primary structure of proteins
 It is the order in which aa are
linked together in a protein.
 Insulin, the hormone that
regulates blood-glucose
levels, was the first protein for
which primary structure was
determined.
 Secondary structure of proteins
 Secondary protein structure is
the arrangement in space
adopted by the backbone
portion of a protein. The two
most common types of
secondary structures are the
alpha helix (α helix) and the
beta pleated sheet (β pleated
sheet).
 Secondary structure of proteins
THE ALPHA HELIX
An alpha helix structure is a
protein secondary structure in
which a single protein chain
adopts a shape that resembles a
coiled spring (helix), with the coil
configuration maintained by
hydrogen bonds.
 Secondary structure of proteins
THE BETA PLEATED SHEET
A beta pleated sheet
structure is a protein structure
on which two fully extended
protein chain segments in the
same or different molecules are
held together by hydrogen
bonds.
 Secondary structure of proteins
 Hydrogen bonds form between oxygen and hydrogen peptide
linkage atoms that are either in different parts of a single chain
that folds back on itself (intrachain bonds) or between atoms in
different peptide chains in those proteins that contain more than
one chain (interchain bonds). In molecules where the β pleated
sheet involves a single molecule, several U-turns in the protein chain
arrangement are needed in order to form the structure.
 Tertiary structure of proteins
 Tertiary protein structure is the overall three-
dimensional shape of a protein that results from the
interactions between aa side chains (R groups) that are
widely separated from each other within a peptide chain.
 The primary structure is the long, straight cord. The
coiling of the cord into a helical arrangement gives the
secondary structure. The supercoiling arrangement of the
cord adopts after you hang up the receiver is the tertiary
structure.
 Quaternary structure of proteins
 It is the highest level of protein organization. It is found
only in multimeric proteins. Quaternary protein
structure is the organization among the various peptide
chains in a multimeric protein.
 An example of a protein with quaternary structure is
hemoglobin, the oxygen-carrying protein in blood. It is a
tetramer in which there are two identical α chains and two
identical β chains. Each chain enfolds a heme group, the site
where oxygen binds to the protein.
 Protein classification based on shape
 Three main types of proteins: fibrous, globular and
membrane.
 A fibrous protein is a protein whose molecules have an
elongated shape with one dimension much longer than
the others. A globular protein is a protein whose
molecules have peptide chains that are folded into
spherical or globular shapes.
 Protein classification based on shape
A membrane protein is a protein that is found
associated with a membrane system of a cell. They
tend to be water-insoluble and they usually have
fewer hydrophobic aa than globular proteins.
 Comparison of fibrous and globular
proteins in terms of general properties
1. fibrous proteins are water-insoluble, whereas globular
proteins dissolve in water. This enables globular proteins to
travel through the blood and other body fluids to sites where
activity is needed.
2. fibrous proteins usually have a single type of secondary
structure whereas globular often contain several types of
secondary structure.
 Comparison of fibrous and globular
proteins in terms of general properties
3. fibrous proteins generally have structural functions that provide
support and external protection, whereas globular are involved in
metabolic chemistry, performing functions such as catalysis,
transport and regulation.
4. the number of different kinds of globular protein far exceeds the
number of different kinds of fibrous protein. Because the most
abundant proteins in the human body are fibrous proteins rather
than globular proteins, the total mass of fibrous present exceeds the
total mass of globular proteins present.
Characteristics of two fibrous proteins and
two globular proteins
1. α keratin
It is particularly abundant in nature, where it is found in
protective coatings for organisms.
 Characteristics of two fibrous
proteins and two globular proteins
The individual molecules are almost wholly α helical. Pairs of these helices
twine about one another to produce a coiled coil. In hair, two of the coiled
coils then further twist together to form a protofilament. Protofilaments
then coil together in groups of four to form microfilaments, which become
the “core "unit the structure of the α keratin of hair.
Natural silk (silkworm silk) and spider silk (spider webs) are made of
fibroin, a fibrous protein that exists mainly in a beta pleated sheet form.
 Characteristics of two fibrous
proteins and two globular proteins
2. Collagen
The most abundant of all proteins in humans (30% of total
body protein). The predominant structural feature within
collagen molecules is a triple helix formed when three
chains of aa wrap around each other to give a ropelike
arrangement of polypeptide chains.
Collagen molecules (triple helices) are very long, thin and
rigid.
Characteristics of two fibrous proteins and
two globular proteins
3. Hemoglobin
The globular protein that transports
oxygen from the lungs to tissue.
The hemoglobin of a fetus is slightly
different in structure from adult
hemoglobin. Called fetal hemoglobin,
this hemoglobin has a greater affinity
for oxygen than the mother’s
hemoglobin.
Characteristics of two fibrous proteins and
two globular proteins
4. Myoglobin
It functions as an
oxygen storage
molecule in muscles.
The function of
hemoglobin is oxygen
transfer and the
myoglobin is oxygen
storage.
Protein classification based on function
1. catalytic proteins. Proteins are probably
best known for their role as catalysts. Proteins
with the role of biochemical catalyst are called
enzymes.
2. defense proteins. These proteins, also
called immunoglobulins or antibodies are
central to the functioning of the body’s immune
system. They bind to foreign substances, such
as bacteria and viruses, to help combat invasion
of the body by foreign particles.
Protein classification based on function
3. transport proteins. These proteins bind to
particular small biomolecules and transport them to
other locations in the body and then release the
small molecules as needed at the destination
location.
4. messenger proteins. These proteins transmit
signals to coordinate biochemical processes
between different cells, tissues and organs. A
number of hormones that regulate body processes
are messenger proteins, including insulin &
glucagon.
Protein classification based on function

5. structural proteins. These proteins confer

stiffness and rigidity to otherwise fluid-like
biochemical systems.
6. transmembrane proteins. These proteins,
which span a cell membrane help control the
movement of small molecules and ions
through the cell membrane.
Protein classification based on function

7. storage proteins. These proteins bind (and

store) small molecules for future use.
8. regulatory proteins. These proteins are
often found “embedded” in the exterior surface
of cell membranes. They act as sites at which
messenger molecules, including messenger
proteins such as insulin, can bind and thereby
initiate the effect that the messenger “carries.
 Protein classification based on function
9. nutrient proteins. These are particularly important in the early
stages of life, from embryo to infant. Casein, found in milk, and
ovalalbumin found in egg white, are the two examples.
 Protein hydrolysis
• When a protein or smaller peptide in a solution of strong acid or
base is heated, the peptide bonds of the aa are hydrolyzed and
free aa are produced. The hydrolysis reaction is the reverse of the
formation reaction for a peptide bond. Amine and carboxylic acid
functional groups are regenerated.
• Protein digestion is simply enzyme-catalyzed hydrolysis of
ingested protein. The free aa produced from this process are
absorbed through the intestinal wall into the bloodstream and
transported to the liver. Here they become the raw materials for
the synthesis of new protein.
 Protein denaturation
• Protein Denaturation is the partial or complete
disorganization of a protein’s characteristic three-
dimensional shape as result of disruption of its
secondary, tertiary, and quaternary structural
interactions.
• A consequence of protein denaturation, the partial
or complete loss of a protein’s three-dimensional
structure, is loss of biochemical activity for the
protein.
 Protein denaturation

• When protein-containing foods are cooked, protein denaturation

occurs. Such “cooked” protein is more easily digested because it
is easier for digestive enzymes to “work on” denatured protein.
Cooking foods also kills microorganisms through protein
denaturation. Like ham and bacon can harbor parasites that
cause trichinosis. In surgery, heat is often used to seal small
blood vessels. This process is called cauterization. Small wounds
can also be sealed by cauterization. Heat-induced denaturation is
used in sterilizing surgical instruments and in canning foods;
bacteria are destroyed when the heat denatures their protein.
 Protein denaturation
Alcohols are an important type of denaturing agent.
Denaturation of bacterial protein takes place when isopropyl
or ethyl alcohol is used as a disinfectant – hence the
common practice of swabbing the skin with alcohol before
giving an infection. Pure isopropyl or ethyl alcohol is less
effective than the commonly used 70% alcohol solution.
 glycoproteins
• It is a protein that contains carbohydrates or carbohydrate
derivatives in addition to aa. The blood group markers of the ABO
system are also glycoproteins in which the carbohydrate content
can reach 85%.
 collagen
• The fibrous protein collagen,
qualifies as a glycoprotein
because carbohydrate units
are present in its structure.
• The presence of carbohydrate
units (mostly glucose,
galactose & their
disaccharides) attached by
glycosidic linkages to collagen
at its 5-hydroxylsine residues
causes collagen to be
classified as glycoprotein.
 immunoglobulins
• It is a glycoprotein produced by an organism as a
protective response to the invasion of microorganisms or
foreign molecules. They serve as antibodies to combat
invasion of the body by antigens. An antigen is a foreign
substance, such as a bacterium or virus, that invades the
human body. An antibody is a biochemical molecule that
counteracts a specific antigen.
 immunoglobulins
1. 4 polypeptide chains are present:2 identical
heavy (H) chains & 2 identical light (L) chains.
2. the H chains which usually contain 400-500
aa residues, are approximately twice as long
as the L chains.
3. both the H & L chains have constant &
variable regions. The constant regions have
the same different aa sequence from
immunoglobulin to immunoglobulin, and the
variable regions have a different aa sequence
in each immunoglobulin.
 immunoglobulins
4. the carbohydrate content of various immunoglobulins
varies from 1% to 12% by mass.
5. the secondary & tertiary structures are similar for all
immunoglobulins. They involve a Y-shaped conformation
with disulfide linkages between H & L stabilizing the
structure.
immunoglobulins
 immunoglobulins
• The importance of immunoglobulins is amply and tragically demonstrated by
the effects of AIDS (acquired immunodeficiency syndrome).its virus upsets
the body’s normal production of immunoglobulins and leaves the body
susceptible to what would otherwise not be debilitating & deadly infections.
• Individuals who receive organ transplants must be given drugs to suppress
the production of immunoglobulins against foreign proteins in the new organ,
thus preventing rejection of the organ. The major reason for the increasing
importance of organ transplants is the successful development of drugs that
can properly manipulate the body’s immune system.
 Classes of immunoglobulins
• The five primary classes of immunoglobulins are IgG,
IgM, IgA, IgD and IgE. These are distinguished by the
type of heavy chain found in the molecule. IgG molecules
have heavy chains known as gamma-chains; IgMs have
mu-chains; IgAs have alpha-chains; IgEs have epsilon-
chains; and IgDs have delta-chains.
Properties of IgG:
• Molecular weight: 150,000
• H-chain type (MW): gamma
(53,000)
• Serum concentration: 10 to 16
mg/mL
• Percent of total
immunoglobulin: 75%
• Glycosylation (by weight): 3%
• Distribution: intra- and
extravascular
• Function: secondary response
Subclasses of immunoglobulins
In addition to the major immunoglobulin classes, several Ig
subclasses exist in all members of a particular animal species.
Antibodies are classified into subclasses based on minor differences
in the heavy chain type of each Ig class. In humans there are four
subclasses of IgG: IgG1, IgG2, IgG3 and IgG4 (numbered in order
of decreasing concentration in serum).
• Properties of IgM:
• Molecular weight: 900,000
• H-chain type (MW): mu (65,000)
• Serum concentration: 0.5 to 2
mg/mL
• Percent of total immunoglobulin:
10%
• Glycosylation (by weight): 12%
• Distribution: mostly intravascular
• Function: primary response
Properties of IgA:
• Molecular weight: 320,000
(secretory)
• H-chain type (MW): alpha
(55,000)
• Serum concentration: 1 to 4
mg/mL
• Percent of total
immunoglobulin: 15%
• Glycosylation (by weight):
10%
• Distribution: intravascular and
secretions
• Function: protect mucus
membranes
Properties of IgD:
• Molecular weight: 180,000
• H-chain type (MW): delta
(70,000)
• Serum concentration: 0 to 0.4
mg/mL
• Percent of total
immunoglobulin: 0.2%
• Glycosylation (by weight):
13%
• Distribution: lymphocyte
surface
• Function: unknown
Properties of IgE:
• Molecular weight: 200,000
• H-chain type (MW): epsilon
(73,000)
• Serum concentration: 10 to 400
ng/mL
• Percent of total immunoglobulin:
0.002%
• Glycosylation (by weight): 12%
• Distribution: basophils and mast
cells in saliva and nasal
secretions
• Function: protect against
parasites
 lipoproteins
• A lipoprotein is a conjugated protein that contains lipids in addition to aa.
The major function is to help suspend lipids and transport them through the
bloodstream. They are in general insoluble in blood because of their nonpolar
nature.
• A plasma lipoprotein is a lipoprotein that is involved in the transport system
for lipids in the bloodstream. These proteins have a spherical structure that
involves a central core of lipid material surrounded by a shell of
phospholipids, cholesterol & proteins. In the blood, cholesterol exists
primarily in the form of cholesterol esters formed from the esterification of
cholesterol’s hydroxyl group with a fatty acid.
lipoproteins
 Four major classes of plasma lipoproteins:
1. chylomicrons. Their function is to transport
dietary triacyglycerols from the intestine to the liver
and to adipose tissue.
2. very low density lipoprotein(VLDL). Their
function is to transport triacyglycerols synthesized
in the liver to adipose tissue.
3. low density lipoprotein(LDL). Their function is
to transport cholesterol synthesized in the liver to
cells throughout the body.
4. high density lipoprotein(HDL). Their function is
to collect excess cholesterol from body tissues and
transport it back to the liver for degradation to bile
acids.
 lipoproteins
• The density of a lipoprotein is related to the fractions of protein
and lipid material present. The greater the amount of protein in
the lipoprotein, the higher the density.
• The presence or absence of various types of lipoproteins in the
blood appears to have implications for the health of the heart and
blood vessels. Lipoprotein levels in the blood are now used as an
indicator of heart disease risk.