PROTEINS

PROTEINS

a naturally occurring, unbranched

polymer in which the monomer units
are AMINO ACIDS.
from the Greek word “proteios” which
means “of first importance”.
AMINO ACIDS
 CLASSIFICATION OF AMINO ACIDS

1. Nonpolar amino acids

2. Polar neutral/uncharged amino acids
3. Polar acidic amino acids/ negatively
charged R group
4. Polar basic amino acids/ positively
charged R groups
NONPOLAR AMINO ACIDS

Contains one amino group, one carboxyl

group, and a nonpolar side chain.
The side chain of proline and its α-amino
group form a ring structure.
Proline gives the fibrous structure of
collagen, and interrupts the α-helices found in
globular proteins.
 POLAR NEUTRAL AMINO ACIDS

 Contains one amino group, one carboxyl group and a side chain
that is polar but neutral.
 More hydrophilic because they form hydrogen bonds with water.
 Includes serine, threonine, cysteine, asparagine, and
glutamine.
 Cysteine contains a sulfhydryl group (-SH), an important
component of the active site of many enzymes.
• Two cysteines can become oxidized to form a dimer cystine,
which contains a covalent cross-link called a disulfide bond (-
S-S-).
 POLAR ACIDIC AMINO
ACID
Contains one amino group and two carboxyl
groups, the second carboxyl group being part of
the side chain.
Aspartic and glutamic acid are proton donors.
At neutral pH, the side chains of these amino
acids are fully ionized.
They have a negatively charged carboxylate
group (-COO-) at physiologic pH.
 POLAR BASIC AMINO
ACID
 Contains two amino groups and one carboxyl group, the
second amino group being part of the side chain.
 The R groups have significant positive charge.
 Lysine has a second positive amino group at the ε
position on its (R) chain.
 Arginine has a positively charged guanidino group.
 Histidine has a positive imidazole group facilitates the
enzyme-catalyzed reaction by serving as a proton
donor/acceptor.
ESSENTIAL AMINO ACIDS

are standard amino acids needed for protein synthesis

that must be obtained from dietary sources because
the human body cannot synthesize it in adequate
amounts from other substances.
Essential amino acids
Arginine Methionine
Histidine Phenylalanine
Isoleucine Threonine
Leucine Tryptophan
Lysine Valine
Complete Dietary Protein
 A protein that contains all of the essential amino acids in the
same relative amounts in which the body needs them.
Incomplete Dietary Protein
 A protein that does not contain adequate amounts, relative to
the body’s needs, of one or more of the essential amino acids.
Complementary Dietary Proteins
 Are two or more incomplete dietary proteins that when
combined, provide an adequate amount of all essential amino
acids relative to the body’s needs.
BIOLOGIC FUNCTIONS OF
SOME AMINO ACIDS
Histidine
 this amino acid is also known for being a precursor of histamine
 regulate and utilize essential trace elements
Arginine
 proved to be a precursor of nitric oxide which causes a blood vessel
relaxation.
 may be useful under many body conditions, including colds, high blood
pressure, migraines, congestive heart failure
Lysine
It plays a major role in calcium absorption
Aids in recovering from surgery or traumas and helps your
body produce hormones, enzymes, and antibodies.
With antiseizure properties.
It is vital for proper growth and plays an important role in the
production of carnitine
Play an essential role in the formation of collagen
Leucine
 which helps in regulating the blood-sugar levels
 promotes the growth and the recovery of muscle and bone tissues during
stress and injury
 Assist in the production of the growth hormone.
Cysteine
 This amino acid provides resistance to the body against all harmful effects
 Cysteine is also necessary for the proper functioning of the skin and helps
your body recover from surgery.
 Cysteine is also used to produce Glutathione and Taurine
Alanine
 This amino acid is synthesized by reductive deamination of pyruvate, and
participates in sugar and acid metabolism.
 It is also known for increasing immunity and providing energy for brain and
central nervous system, let alone the muscle tissue.
Proline
 an essential component of collagen, and therefore is vital for proper
functioning of joints and tendons.
 Besides, this amino acid helps maintain and strengthen heart muscles.
Tyrosine
 is known worldwide for supporting and assisting neurotransmitters in the brain.
 essential for the production of a number of important hormones like thyroxine
Asparagine
 also known for its key role in the biosynthesis of glycoproteins.
 Human nervous system also needs this amino acid to be able to maintain an
equilibrium.
Glutamine
 the most active amino acid involved in lots of metabolic processes.
 it also participates in maintaining of a normal blood glucose level and the
proper pH range.
 A human body utilizes this amino acid at high rates for rapidly dividing cells,
like leukocytes, in order to supply them with an energy
 Precursor of GABA
Glycine
 is the first of all necessary ones for a healthy digestive system
 also plays a role as an inhibitory neurotransmitter in your central nervous
system
 is essential for the development and quality of human skeletal muscles,
tissues, and structural integrity, as well as for the synthesis of nucleic acids.
 helps prevent the breakdown of muscles, because it can boost your body's
levels of creatine
Serine
plays an important role in various biosynthetic pathways.
it also helps an enzyme catalyze its reaction
also known for assisting in production of immunoglobulins
and antibodies for a healthy immune system
 PEPTIDE

Is an unbranched chain of amino acids.

Further classified by the number of amino acids
present in the chain.
a. Dipeptide
b. Tripeptide
c. Oligopeptide
d. Polypeptide
 Nature of peptide bond

Peptide bond is a covalent bond between the carboxyl group of one amino acid
and the amino group of another amino acid.
Nature of peptide bond
Nature of peptide bond
Nature of peptide bond
Nature of peptide bond
 Peptide nomenclature
• Rule 1: The C-terminal amino acid residue keeps its full amino acid
name.
• Rule 2: All of the other amino acid residues have names that end in
–yl. The –yl suffix replaces the –ine or –ic acid ending of the
amino acid name, except for the following:
• Tryptophan (tryptophyl)
• Cysteine (cysteinyl)
• Glutamine (glutaminyl)
• Asparagine (asparaginyl)
• Rule 3: The amino acid naming sequence begins at the N-terminal
amino acid residue.
BIOCHEMICALLY IMPORTANT
SMALL PEPTIDES
 Small Peptide Hormones

Oxytocin and Vasopressin are nonapeptide.

Oxytocin- regulates uterine contractions and lactation
Vasopressin- regulates water excretion by the kidneys
Small Peptide Neurotransmitters

Enkephalins are pentapeptide neurotransmitters

produced by the brain itself that bind at receptor
sites in the brain to reduce pain.
e.g. Met-enkephalin, Leu-enkephalin
 Small Peptide Antioxidants

Glutathione is a tripeptide present in significant

concentrations in most cells. It serves as a regulator
of oxidation-reduction reactions.
 GENERAL STRUCTURAL
CHARACTERISTICS OF PROTEINS

Protein- is a peptide in which at least 40 amino acid

residues are present.
 Classification based on
peptide chain
a. Monomeric protein
Is a protein in which only one peptide chain
is present.
b. Multimeric protein
Is a protein in which more than one peptide
chain is present.
 Classification based on
chemical composition
a. Simple protein
Is a protein in which only amino acid
residues are present.
b. 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.
 TYPES OF CONJUGATED PROTEINS
CLASS PROSTHETIC SPECIFIC EXAMPLE FUNCTION OF EXAMPLE
GROUP
Hemoproteins Heme unit Hemoglobin Carrier of Oxygen in blood
Myoglobin Oxygen binder in muscles
Lipoproteins Lipid LDL Lipid carrier
HDL Lipid carrier
Glycoproteins Carbohydrate Gamma globulin Antibody
Mucin Lubricant in mucous secretions
Interferon Antiviral protection
Phosphoprotei Phosphate group Glycogen Enzyme in glycogen
ns phosphorylase phosphorylation
Nucleoproteins Nucleic acid Ribosomes Site for protein synthesis in cells
Viruses Self-replicating, infectious
complex
Metalloproteins Metal ion Iron-ferritin Storage complex for iron
Zinc-alcohol Enzyme in alcohol oxidation
dehydrogenase
 PRIMARY STRUCTURE
Is the order in which amino acids are linked together
in a protein.
Involves more than just the numbers and kinds of
amino acid present
It also involves the order of attachment of the amino
acids to each other through peptide bonds.
Insulin: the hormone that regulates blood-glucose
levels ; first protein for which primary structure was
determined
PRIMARY STRUCTURE
PRIMARY STRUCTURE
SECONDARY STRUCTURE

Is the arrangement in space adopted by the

backbone portion of the protein
the regularly repeating ordered spatial
arrangements of amino acids near each other
in the protein chain
 2 COMMON TYPES OF
SECONDARY STRUCTURE
• ALPHA HELIX
Is a protein
secondary structure
in which a single
protein chain adopts
a shape that
resembles a coiled
spring, with the coil
configuration
maintained by
hydrogen bonds.
 ALPHA HELIX STRUCTURE

1. The twist of the helix forms a right-handed, or clockwise,

spiral.
2. The hydrogen bonds between C=O and N-H entities are
orientated parallel to the axis of the helix
3. A given hydrogen bond involves a C=O group of one
amino acid and an N-H group of another amino acid
located four amino acid residues further along the spiral.
4. All of the amino acid R groups extend outward from the
spiral. There is no enough room for the R groups within the
spiral
 2 COMMON TYPES OF
SECONDARY STRUCTURE
• BETA-PLEATED
SHEET
Is a protein
secondary structure
in which two fully
extended protein
chain segments in
the same or
different molecules
are held together by
hydrogen bonds.
 BETA PLEATED SHEET

1. The hydrogen bonds between C=O and N-H entities

lie in the plane of the sheet
2. The amino acid R groups are found above and below
the plane of the sheet and within a given backbone
segment alternating between the top and bottom
positions.
 TERTIARY STRUCTURE
Is the overall three-dimensional shape of a protein that
results from the interactions between amino acid side chains
that are widely separated from each other within a peptide
chain.
INTERACTIONS RESPONSIBLE
FOR TERTIARY STRUCTURES
1. Covalent Disulfide bonds
• Strongest of the tertiary structure interaction
• Result from the –SH group of 2 cysteines
2. Electrostatic attractions
• also called “salt bridges”
• Involves interaction between an acidic side
chain and a basic side chain
3. Hydrogen Bonds
• Occur between amino acids with polar
side chains
4. Hydrophobic Bonds
• result when two nonpolar side chains
are close to each other
 QUATERNARY
STRUCTURE
Highest level of protein organization
Found only in multimeric 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.
Tend to have simpler, regular, linear structures.
• Globular Protein
Is a protein that 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.
FIBROUS (insoluble) GLOBULAR (soluble)
• Keratin – found in wools, silk, • Insulin – regulatory hormone for
fingernails controlling glucose metabolism
• Collagen – found in tendons, • Myoglobin – involve in oxygen
bone and other connective tissue storage in muscles
• Elastins – found in blood vessels • Hemoglobin – involve in oxygen
and ligaments transport in blood
• Myosin – found in muscle tissue • Transferrin- involves in iron
transport in blood
• Fibrin – found in blood clots
• Immunoglobulin - involved in
immune system response
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
 Are central to the functioning of the body’s immune system.
 Also called immunoglobulins or antibodies.
3. TRANSPORT PROTEINS
 Binds 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.
 e.g. Hemoglobin
Transferrin
HDL and LDL
4. MESSENGER PROTEINS
 Proteins that transmit signals to coordinate biochemical processes between
different cells, tissues and organs.
 e.g. insulin, glucagon, human growth hormone
5. CONTRACTILE PROTEINS
 Are necessary for all forms of movement.
 e.g. actin, myosin
6. STRUCTURAL PROTEINS
 Confer stiffness and rigidity and rigidity to otherwise fluid-like biochemical
systems.
 e.g. Collagen
α-keratin
7. TRANSMEMBRANE PROTEINS
 Help control the movement of small molecules and ions through the cell
membrane.
8. STORAGE PROTEINS
 These proteins bind small molecules for future use.
 e.g. myoglobin
9. REGULATORY PROTEINS
 Often found “embedded” in the exterior surface of cell membranes.
 Are often the molecules that bind to enzymes thereby turning them “on”
or “off ” and thus controlling enzymatic action.
10. NUTRIENT PROTEINS
Are particularly important in the early stages of life, from
embryo to infant.
e.g. casein, ovalbumin
11. BUFFER PROTEINS
Are part of the system by which the acid-base balance within
body fluids is maintained.
e.g. Hemoglobin, transmembrane proteins
12. FLUID-BALANCE PROTEINS
Help maintain fluid balance between blood and surrounding
tissue.
e.g. Albumin, globulin
PROPERTIES OF
PROTEINS
 Protein Hydrolysis

• Complete protein hydrolysis

 All peptide bonds are broken freeing up all of the
constituent amino acids
Partial protein hydrolysis
 Some, but not all, of the peptide bonds are broken
producing a product mixture that contains both free amino
acids and small peptides.
 Protein Denaturation

 Is the partial or complete disorganization of a protein’s characteristic

three-dimensional shape as a result of disruption of its secondary, tertiary
and quaternary structural interactions.
 Examples:
a. Egg albumin
b. Cauterization
c. Inactivation of enzymes
d. Curdy precipitate of casein
e. Alcohols
 Selected physical and chemical denaturing agents
Denaturating Agent Mode of Action
Heat Disrupts hydrogen bonds by making molecules
vibrate too violently; produces coagulation
Microwave radiation Causes violent vibration of molecules that disrupt
hydrogen bonds
UV radiation Operates very similar to the action of heat
Violent whipping or shaking Causes molecules in globular shapes to extend to
longer lengths, which then entangle
Detergents Affects R-groups interactions
Organic solvents (e.g., ethanol, 2- Interferes with R-group interactions because these
propanol,acetone) solvents can form hydrogen bonds; quickly denatures
proteins in bacteria
Strong acids and bases Disrupts hydrogen bonds and salt bridges
Salts of heavy metals Metal ions combine with –SH groups and form
poisonous salts
Reducing agents Reduces disulfide linkages to produce –SH
 Reaction of Proteins with Heat

Heat disrupts hydrogen bonding and nonpolar

hydrophobic bonding
used in sterilization to denature and hence destroy
the enzymes in bacteria.
(+) coagulation
 Reaction with pH

 Changes in pH disrupts H-bonds

and salt bridges, causing
irreversible denaturation
• (+) yellow coagulate (HNO3)
• (+) white coagulate (HCl)
• Principle used in Heller’s ring test:
(+) white ring in the interface of
two liquids
 Reaction with Alcohol

Ethanol is capable of forming hydrogen bonds with

protein molecules which will disrupt the hydrogen
bonding within the molecule.
• (+) 95%- greatest amount of coagulation
• (+) 70%- moderate amount of coagulation
• (+) 40%- least amount of coagulation
 Reaction with Salts of Heavy
Metals
Salts of metal ions such as mercury(II), lead(II), and
silver can form strong bonds with disulfide groups
of the protein.
Thus, they disrupt both disulfide bridges and salt
linkages and cause the protein to precipitate out of
solution as an insoluble metal-protein salt.
 Reaction with Alkaloidal
Reagents
• Forms insoluble compounds with CHON
• (+) picric acid- yellow coagulate
• (+) tannic acid- flesh coagulate
• (+) TCA- milky white coagulate
AMINO ACID DISORDERS
 Phenylketonuria
CAUSE SYMPTOMS TREATMENT
• PKU is caused by a • Seizures  Avoid foods high in
defect in the gene that • Tremors, or trembling protein
helps create and shaking  Medication:
phenylalanine • Stunted growth Sapropterin (Kuvan)
hydroxylase • Hyperactivity
• Unable to break • A musty odor of their
down phenylalanine breath, skin, or urine
• This causes a
buildup of
phenylalanine in the
body
 Methyl Malonic Aciduria
CAUSE SYMPTOMS TREATMENT
• Methyl malonic • Neurologic  Protein-restricted diet- this
acidemia is an manifestations, such modification decreases the key amino
autosomal as seizure, acids (eg, isoleucine, valine,
recessive disorder encephalopathy, and threonine, methionine) that enter the
of amino acid stroke metabolic pathway.
metabolism, • Several cases have  Cobalamin supplementation- may
involving a defect involved stroke help because cobalamin is a cofactor
in the conversion in the enzymatic conversion of
of methylmalonyl- methylmalonyl-coenzyme A (CoA) to
coenzyme A (CoA) succinyl-CoA.
to succinyl-CoA
 Maple Syrup Urine Disease
CAUSE SYMPTOMS TREATMENT
Deficiency of branched- • loss of appetite  Dietary restriction of
chain alpha-keto acid • fussiness the amino acids
dehydrogenase complex • sweet-smelling urine leucine, isoleucine,
(BCKDC), leading to a and valine.
buildup of the branched-  Intravenous solution
chain amino acids (leucine, that helps the body
use up excess leucine,
isoleucine, and valine) and
isoleucine, and valine
their toxic by-products
for protein synthesis.
(ketoacids) in the blood and  Gene therapy
urine.
 Parkinson’s Disease
CAUSE SYMPTOMS TREATMENT
progressive neurological Symptoms of • Medicines: such as levodopa and dopamine
disorder that is caused by a Parkinson's disease agonists.
degeneration of cells in the differ from person to • Brain surgery: for example deep brain
part of the brain that person stimulation (DBS), may be considered when
produces the • lowness of voluntary medicine fails to control symptoms of Parkinson's
neurotransmitter dopamine movements, especially disease or causes severe or disabling side effects.
(chemical messenger) in the initiation of • Speech therapy: Speech therapists use breathing
such movements as and speech exercises to help you overcome the
walking or rolling over soft, imprecise speech and monotone voice that
in bed develop in advanced Parkinson's disease.
• A shuffling gait with • Physical therapy: Therapists may help you
poor arm swing and improve your walking and reduce your risk of
stooped posture falling.
• Unsteady balance; • Occupational therapy: Therapists can help you
difficulty rising from a learn new ways to do things for yourself so you
sitting position can stay independent longer.
 Homocystinuria
CAUSE SYMPTOMS TREATMENT
 may be due to dietary deficiencies in • dislocation of the lenses • High doses of vitamin
vitamin B6, vitamin B12, and folic in the eyes B-6 are a successful
acid. • nearsightedness treatment for about half
 Certain genetic mutations present at • abnormal blood clots of the people with this
birth cause this disease. • osteoporosis, or disorder.
 The CBS (Cystathionine-Beta- weakening of the bones • Eating a diet low in
Synthase) gene holds instructions for • learning disabilities foods containing the
making an enzyme that uses vitamin • developmental problems amino acid Methionine
B-6 to metabolize the amino acids • chest deformities, such as
homocysteine and serine. a protrusion or a caved-in
 The mutations prevent the normal appearance of the
functioning of the CBS gene. breastbone
 This results in a buildup of • long, spindly arms and
homocysteine and other toxins that legs
damage the nervous system, which • scoliosis
includes the brain, and the vascular
system
 Hartnup’s disease
CAUSE SYMPTOMS TREATMENT
 disease is caused by a • sensitivity to light • consists of a change in diet,
mutation(six • anxiety avoidance of sunlight, and
mutations in • rapid mood swings prescribing sulfonamide drugs
SLC6A19) of the gene • hallucinations • Consuming foods that contain
that controls the • delusions the B-complex vitamin niacin
processes of amino • intention tremor can significantly reduce your
acid (Trp, His) • speech difficulties symptoms.
absorption and • abnormalities in muscle • Good sources of niacin
reabsorption tone: either muscles can include: meat, poultry, fish,
become more tight fortified and whole grains,
peanut butter, potatoes B-
complex or niacin vitamin
supplements (such as nicotinic
acid)
 Albinism

CAUSE SYMPTOMS
 Is a result of a problem in  a person with albinism may not
the biochemical pathway always have a pale complexion,
that converts phenylalanine white hair and pink eyes.
to melanin.  can sometimes vary from other
 Results from the absence of family members by having a
tyrosinase lighter skin tone.
 Alkaptonuria

CAUSE SYMPTOMS
 is a rare inherited genetic  Earwax turns to black
disorder of phenylalanine  dark spots in the sclera (white)
and tyrosine metabolism. of your eyes.
 Due to the absence of
homogentisate oxidase