Proteins

What are proteins?

• Protein – are organic compound composed of
one or more polypeptide chains of amino acids.
• The very word “protein” is derived from the
Greek proteios, meaning “of first importance”,
and the scientist who named these compounds
more than 100 years ago choose an appropriate
term.
Major types of proteins
• Fibrous proteins – which are insoluble in
water and are used mainly for structural
purposes.
• Globular proteins – which are more or less
soluble in water and are used mainly for
nonstructural purposes.
What are amino acids?
• Is an organic compound containing an amino
group and an acid group.
• Alpha – the 20 amino acids found in proteins.
• Organic chemistry can synthesize many
thousands of amino acids, but nature is much
more restrictive and uses only 20 different
amino acids to make up proteins. Furthermore,
all but one of the 20 fit the formula
What are amino acids?
H
|
R-C-COOH
|
NH2

and even the one that doesn’t fit the formula

(praline) comes pretty close. Proline would fit
except that it has a bond between the R and N.
the 20 amino acids found in proteins are called
alpha amino acids.
What are zwitterions?
• Amino acids in the solid state, as well as in
water, carry both positive and negative charges;
they are called zwitterions.
• The pH at which the number of positive charges
equals the number of negative charges is the
isoelectric point of an amino acid or protein.
What are zwitterions?
• Zwitterions (the word is derived from the
German for "hybrid ion") are ions that are
electrically neutral overall but contain
nonadjacent regions of positive and negative
charges; they are sometimes referred to as
"dipolar ions." The best-known examples of
zwitterions are the free amino acids found in
cells.
How do amino acids combine to form
proteins?
• When the amino group of one amino acid
condenses with the carboxyl group of another
amino acid, an amide (peptide) bond is formes,
with the elimination of water.
• Two amino acids from a dipeptide. Three amino
acids form a tripeptide.
• Many amino acids form a polypeptide chain.
Proteins are made of one or more polypeptide
chains.
Biochemically important small
peptides
• Hormonal function
• Neurotransmission
• Antioxidant activity
Small peptide hormones
• The two best known peptide hormone, both
produced by pituitary gland, are oxytocin and
vasopressin.
• Each hormone is a nanopeptide with six of the
residues held in the form of a loop by a disulfide
bond formed from the interaction of two cysteine
residues.
• Oxytocin regulates uterine contractions and
lactations.
• Vasopressin regulates excretion of water from the
kidneys; it also affects blood pressure.
Small peptide neurotransmitters

• Enkephalins are pentapeptide

neurotransmitters produced by the brain itself
that bind at the receptor sites in the brain to
reduce pain.
• The two best know enkephalins are Met-
enkephalin and Leu-enkephalin
▫ Met-enkephalin: Tyr-Gly-Gly-Phe-Met
▫ Leu-enkephalin: Tyr-Gly-Gly-Phe-Leu
Small peptide antioxidants
• The tripeptide glutathione (Glu-Cys-Gly) is
present in significant concentrations in most
cells and is of considerable physiological
importance as a regulator of redox reactions.

• Glutathione functions as antioxidant, protecting

cellular contents from oxidizing agents such as
peroxides and superoxides.
 General structural characteristics of
proteins
• Proteins are classified as monomeric or multimeric.
• Monomeric protein is a protein in which only one
peptide chain is present.
• 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.
▫ The small protein insulin is a multimeric protein with
two protein subunits; one subunit contains 21 amino
acid residues and the other 30 amino acid residues
• Proteins on the basis of chemical composition,
are classified as simple or complex.
• A simple protein is a protein in which only
amino acid residues are present.
• A conjugated protein is a protein that has one or
more non amino acid entities present in its
structure in addition to one or more peptide
chains.
• A prosthetic group is a non-amino acid group
present in a conjugated protein.
• Conjugated proteins may be further classified
according to the nature of the prosthetic group
present.
▫ Lipoproteins contain lipid prosthetic group
▫ Glycoproteins – carbohydrates
▫ Hemoproteins – heme unit
▫ Phosphoproteins – phosphate group
▫ Nucleoproteins –nucleic acid
▫ Metalloproteins – metal ion
 Class Specific Function
Example

Hemoproteins Hemoglobin Carrier of oxygen in blood

myoglobin Oxygen binder in muscles

Lipoproteins LDL Lipid carrier

HDL

Glycoproteins Gamma globulin Antibody

Mucin Lubricant in mucous secretions
Interferon Antiviral infection

Phosphoproteins Glycogen Enzyme in glycogen phosphorylation

phosphorylase

Nucleoproteins Ribosomes Site for protein synthesis in cells

Virus Self-replicating, infectious complex

Metalloproteins Iron-ferritin Storage complex for iron

Zinc-alcohol Enzyme in alcohol oxidation
dehydrogenase
General structure of protein
• Primary structure – the sequence of amino
acids present in a protein’s peptide chain or
chains
• Secondary – the regularly repeating ordered
spatial arrangements of amino acids near each
other in the protein chain, which result from
hydrogen bonds between carbonyl oxygen atoms
and amino hydrogen atoms.
▫ Alpha helix – H bonds every fourth amino acid
▫ Beta pleated sheet – H bonds between two side-
by-side chains, or a single chain that is folded back
on itself
• Tertiary structure – the overall three-
dimensional shape that results from the
attractive forces between amino acid chain
▫ Disulfide bonds
▫ Electrostatic interactions
▫ H bonds
▫ Hydrophobic interactions
• Quarternary structure - The three-
dimensional shape of a protein consisting of two
or more independent peptide chains, which
results from noncovalent interactions between R
groups.
• Quarternary structure
▫ Hemoglobin
▫ Collagen
▫ Integral membrane proteins
Protein classification based on shape
• Fibrous protein is a protein whose molecules
have an elongated shape with one dimension
much longer than the others.
• Globular protein is a protein whose molecules
have peptide chains that are folded into
spherical or globular shapes
• Membrane protein is a protein that is found
associated with a membrane system of a cell.
 Some common Fibrous and Globular Proteins

Name Occurrence and function

Fibrous proteins
Keratins Found in wool, feathers, hooves, silk and fingernails
Collagens Tendons, bones and other connective tissues
Elastins Blood vessels and ligaments
Myosins Muscle tissue
Fibrin Blood clots

Globular Proteins
Insulin Regulatory hormone for controlling glucose metabolism
Myoglobin Involved in oxygen storage in muscles
Hemoglobin Involved in oxygen transport in blood
Transferrin Involved in iron transport in blood
Immunoglobulins Involved in immune system responses
Keratin
• Keratin, a fibrous protein of hair, fingernails,
horns and wool, is one protein that does have a
predominantly α–helix structure. Silk is made of
fibroin, another fibrous protein, which exists
mainly in the pleated sheet form. Silkworm silk
and especially spider silk exhibit a combination
of strength and toughness unmatched by high-
performance synthetic fibers.
 Collagen
• Collagen, the most abundant of all proteins in
humans (30% of total body protein), is a major
structural material in tendons, ligaments, blood
vessels, and skin; it is also the organic component of
bones and teeth.
• The predominant structural feature within collagen
molecules is a triple helix formed when three chains
of amino acids wrap around each other to give a rope-
like arrangement.
• The rich content of the amino acid proline in collagen
is one reason why it has a triple-helix conformation.
Hemoglobin
• The globular protein hemoglobin transports
oxygen from the lungs to tissue. It is a tetramer
(4 peptide chains) with each subunit also
containing a heme group.
Myoglobin
• Myoglobin is a monomer, consists of a single
peptide chain and a heme unit, thus only one
unit oxygen molecule can be carried out by a
myoglobin molecule.
Protein classification based on
function
1. Catalytic Proteins
▫ Proteins with role of biochemical catalysts are
call 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 in the body
by foreign substances.
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.
▫ The most well known example of transport
protein is hemoglobin, which carries oxygen
from the lungs to the organs and tissues.
▫ Another transport protein is transferrin, which
carries iron from the liver to the bone marrow.
▫ High and low-density lipoprotein are carriers of
cholesterol in the bloodstream.
4. Messenger proteins
▫ These proteins transmit signals to coordinate
biochemical processes between different cells,
tissues and organs.
▫ Examples are insulin, glucagon and human
growth hormone (somatotropin).
5. Contractile proteins
▫ These proteins are necessary for all forms of
movement e.g. contraction and extension. Actin
and myosin are examples of such proteins.
Human reproduction depends on the movement
of the sperm. Sperm can “swim” because of the
long flagella made up of contractile proteins.
6. Structural proteins
▫ These proteins confer stiffness and rigidity.
Collagen is a component of cartilage and keratin
gives mechanical strength as well as protective
covering to hair, fingernails, feathers, hooves,
and some animal shells.
7. Transmembrane proteins
▫ These proteins help control the movement of
small molecules ad ions through the cell
membrane. Many transmembrane proteins
function as gateways to permit the transport of
specific substances across the membrane.
▫ alpha-helical and beta-barrels
8. Storage proteins
▫ These proteins bind and store small molecules
for future use. E.g. ferritin, an iron-storage
protein, which saves the iron for use in the
biosynthesis of new hemoglobin molecules.
Myoglobin an oxygen-storage protein present in
muscle; the oxygen so stored is a reserve oxygen
source for working muscle.
9. Regulatory proteins
▫ These proteins are often found “embedded” in
the exterior surface of cell membranes. They
bind to enzymes (catalytic proteins), thereby
turning them “on” and “off”, and thus control
10. Nutrient proteins
▫ These proteins are particularly important in the
early stages of life, from embryo to infant.
▫ Casein found in milk, and ovalbumin, found in
egg white, are the two examples of this protein.
▫ ¾ of the protein in milk is casein, and over 50%
of the protein in egg white is ovalbumin.
▫ The role of milk in nature is to nourish and
provide immunological protection for
mammalian young.
Protein Hydrolysis
• When a protein or smaller peptide in a solution
of strong acid or strong base is heated, the
peptide bonds of the amino acid chain are
hydrolyzed and free amino acids are produced.
Protein denaturation
• It is the partial or complete disorganization of a
protein’s characteristic three-dimensional shape
as a result of disruption of its secondary,
tertiary, and quarternary structural interactions.
• The result of denaturation is loss of biochemical
activity.
• Renaturation is the restoration process by which
proteins are refolded. However for extensive
denaturation changes, the process is usually
irreversible.
Protein denaturation
• Loss of water solubility is a frequent physical
consequence of protein denaturation. The
precipitation out of biochemical solution of
denatured protein is called coagulation.
Protein denaturation
Selected Physical and Chemical Denaturing Agents
Heat Disrupts H bonds by making molecules vibrate too violently;
produces coagulation, as in frying of egg
Microwave Causes violent vibrations of molecules that disrupt H bonds.
radiation
UV radiation Operates very similarly to the action of heat (e.g. sunburning)
Violent whipping Causes molecules on globular shapes to extend to longer
or shaking lengths, which then entangle (e.g. beating egg white into
meringue)
Detergent Affects R-group interactions
Organic solvents Interfere with R-group interactions because these solvents can
(e.g. ethanol, form H bonds; quickly denature proteins in bacteria, killing
acetone) them.
Strong acids and Disrupt H bonds and salt bridges; prolonged action leads to
bases actual hydrolysis of peptide bonds.
Salts of heavy Metal ions combine with –SH groups and form poisonous
metals (e.g. salts of salts
Hg2+, Ag+, Pb2+)

Reducing agents Reduce disulfide linkages and produce –SH groups.

Glycoproteins
• A gylcoprotein is a protein that contains CHO or
carbohydrates derivatives in addition to amino
acids.
• Two proteins involve are collagen and
immunoglobulins.
Lipoproteins
• A conjugated protein that contains lipids in
addition to amino acids.
• The major function of such proteins is to help
suspend lipids and transport them through the
bloodstream
• A plasma lipoprotein is a lipoprotein that is
involved in the transport system of lipids in the
bloodstream.
Four major classes of plasma
lipoproteins
• Chylomicrons – transport dietary triacylglycerols
from the intestine to the liver and to the adipose
tissue.
• Very-low-density lipoproteins (VLDL) – transport
tryacylglycerol synthesized in the liver to adipose
tissue.
• Low-density lipoprotein – transport cholesterol
synthesized in the liver to cells throughout the
body.
• High-density lipoprotein – collect excess
cholesterol from body tissues and transport it back
to the liver for degradation to bile acids.