PROTEINS
The Building Blocks of Life
CHAPTER OUTLINE
3-1
Characteristics of proteins
3-11 Secondary Structure of Proteins
3-2
Amino Acids: The Building Blocks for Proteins
3-12 Tertiary Structure of Proteins
3-3
Essential Amino Acids
3-13 Quaternary Structure of Proteins
3-4
Chirality and Amino Acids
3-14 Protein Hydrolysis
3-5
Acid-Base Properties of Amino Acids
3-15 Protein Denaturation
3-6
Cysteine: A Chemically Unique Amino Acid
3-16 Protein Classification Based on Shape
3-7
Peptides
3-17 Protein Classification Based on Function
3-8
Biochemically Important Small Peptides
3-18 Glycoproteins
3-9
General Structural Characteristics of Proteins
3-19 Lipoproteins
3-10 Primary Structure of Proteins
3-1
Characteristics
of Proteins
Unlocking Protein Secrets: Key Characteristics
PROTEINS!
PROTEINS
most abundant in nearly all cells as they
account for about 15% of a cell’s overall
mass
naturally occurring, unbranched polymer
in which the monomer units are amino
acids.
AVERAGE NITROGEN CONTENT
PHOSPHORUS
IRON
WHAT HAVE YOU LEARNED
Which of the following seta of four elements are always present in
protein
a. C, H, O, S
b. C, H, N, S
c. C, H, O, N
d. C, H, E, S, C, A
Proteins are naturally occurring unbranched polymers in which the
monomers are...
a. monocarboxylic acids
b. dicarboxylic acids
c. amino acids
d. secret
WHAT HAVE YOU LEARNED
Which of the following seta of four elements are always present in
protein
a. C, H, O, S
b. C, H, N, S
c. C, H, O, N
d. C, H, E, S, C, A
Proteins are naturally occurring unbranched polymers in which the
monomers are...
a. monocarboxylic acids
b. dicarboxylic acids
c. amino acids
d. secret
WHAT HAVE YOU LEARNED
Which of the following seta of four elements are always present in
protein
a. C, H, O, S
b. C, H, N, S
c. C, H, O, N
d. C, H, E, S, C, A
Proteins are naturally occurring unbranched polymers in which the
monomers are...
a. monocarboxylic acids
b. dicarboxylic acids
c. amino acids
d. secret
3-2
Amino Acids: The Building
Blocks for Proteins
What are amino acids?
AMINO
ACIDS!
AMINO ACIDS
organic compound that contains both
an amino (NH2) group and a carboxyl
a - amino acids
amino acids in which the amino
group and the carboxyl group are
attached to the a-carbon atom
the R group
present in an a-amino acid called the amino acid
side chain
DID YOU
KNOW?
A STANDARD AMINO ACID
one of the 20 a-amino acids normally found in proteins.
01
02
NONPOLAR AMINO ACID POLAR NEUTRAL AMINO ACID
one amino group, one carboxyl group, and a
nonpolar side chain.
one amino group, one carboxyl group, and a
side chain that is polar but neutral
03
04
POLAR ACIDIC AMINO ACID POLAR BASIC AMINO ACID
one amino group and two carboxyl groups,
the second carboxyl group being part of the
side chain.
two amino groups and one carboxyl group,
the second amino group being part of the side
chain.
NONPOLAR AMINO ACID
When incorporated into a protein, such amino acids are
hydrophobic
They are generally found in the interior of proteins
Trytophan
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.
NONPOLAR AMINO ACID
POLAR NEUTRAL AMINO ACID
SOLUTION AT PHYSIOLOGICAL PH
side chain of a polar neutral amino acid is neither
acidic nor basic.
more soluble in water than the nonpolar amino acids
as, in each case, the R group present can hydrogenbond to water.
POLAR NEUTRAL AMINO ACID
POLAR ACIDIC AMINO ACID
SOLUTION AT PHYSIOLOGICAL PH
side chain of a polar acidic amino acid bears a
negative charge; the side-chain carboxyl group has
lost its acidic hydrogen atom.
ASPARTIC ACID AND GLUTAMIC ACID
POLAR ACIDIC AMINO ACID
POLAR BASIC AMINO ACID
SOLUTION AT PHYSIOLOGICAL PH
the side chain of a polar basic amino acid bears a
positive charge; the nitrogen atom of the amino group
has accepted a proton
LYSINE, ARGININE, AND HISTIDINE
POLAR BASIC AMINO ACID
THE NAMES OF THE STANDARD AMINO ACIDS
Often abbreviated using three-letter codes
Except in four cases, these abbreviations are the first
three letters of the amino acid’s name
About 11 of the 20 standard amino acids can be
synthesized from carbohydrates and lipids in the body
if a source of nitrogen is also available.
The adult human body cannot produce adequate
amounts of the other nine standard amino acids.
3-3
Essential Amino
Acids
Are essential amino acids really “essential?”
ESSENTIAL
AMINO
ACIDS!
ESSENTIAL AMINO ACIDS
standard amino acid needed for protein synthesis that must
be obtained from dietary sources because the human body
cannot synthesize it in adequate amounts from other
substances.
9
10
COMPLETE
DIETARY
PROTEIN
protein that
contains all of the
essential amino
acids in the same
relative amounts in
which the body
needs them.
INCOMPLETE PROTEIN FROM PROTEIN FROM
DIETARY
ANIMAL
PLANT
PROTEIN
SOURCES
SOURCES
protein that does not
contain adequate
amounts, relative to
the body’s needs, of
one or more of the
essential amino acids
usually complete dietary
protein.
GELATIN - one
common incomplete
dietary protein that
comes from animal
sources
tends to be incomplete
dietary protein
LIMITING AMINO
ACIDS - lysine,
methionine,
tryptophan
GENETIC ENGINEERING PROCEDURES
the quality of a given plant’s protein was something that could not be changed.
GENETIC MODIFICATION TECHNIQUES
can improve a plant’s protein by causing it to produce increased amounts of amino acids that
it normally has in short supply
3-4
Chirality and
Amino Acids
hello chirality...and amino acids.. again
CHIRALITY AND AMINO ACIDS
19 of the 20
possess a chiral center this location, so enantiomeric
forms (left- and right-handed forms) exist for each of
these amino acids.
With few exceptions (in some bacteria), the amino
acids found in nature and in proteins are l isomers.
Thus, as is the case with monosaccharides, nature
favors one mirror-image form over the other.
Interestingly, for amino acids the l isomer is the
preferred form, whereas for monosaccharides the d
isomer is preferred.
CHIRALITY AND AMINO ACIDS
FISCHER PROJECTION FORMULA
--COOH group positions the carbon chain vertically
The placement of --NH2 determines if the carbon chain is an L or D isomer
3-5
Acid base
Properties of
Amino Acid
PURE FORM AMINO ACIDS
white crystalline solids with relatively high decomposition points.
Amino acids are not very soluble in water because of strong
intermolecular forces within their crystal structures.
Amino acids are charged species both in the solid state and in
solution:
PURE FORM AMINO ACIDS
In a neutral solution, carboxyl groups have a tendency to lose protons
(H+) producing a negatively charged species.
Also amino groups have a tendency to accept protons (H+) producing a
positively charged species
PURE FORM AMINO ACIDS
Consistent with the behavior of these groups, in a neutral solution, the
–COOH group of an amino acid donates a proton to the NH2 of the
same amino acid.
internal acid base reaction
ZWITTERION
from a German term meaning “double ion”
It is a molecule that has a positive charge on one
atom and a negative charge on another atom, but
has no net charge.
The net charge on a zwitterion is zero even though
part of the molecule carries charges.
ZWITTERION
In the solution, 3 amino acid forms can exist (zwitterion, negative
and positive ion) which are in equilibrium with each other, and
the equilibrium shifts with pH change.
ISOELECTRIC POINTS
the pH at which an amino acid exists
primarily in its zwitterion form.
Every amino acid has a different
isoelectric point. Fifteen of the 20 amino
acids, those with nonpolar or polar
neutral side chains, have isoelectric
points in the range of 4.8-6.3.
Cysteine: A
Chemically
Unique
Amino Acid
3-6
CYSTEINE
an amino acid, a building block of proteins that are
used throughout the body.
Cysteine is the only standard amino acid that has a
side chain that contains a sulfhydryl group.
In the presence of mild oxidizing agents, it readily
dimerizes, that is, reacts with another cysteine
molecule to form a cysteine molecule.
CYSTEINE
In cysteine residues are linked via a covalent disulfide bond
Peptides
3-7
PEPTIDE
an unbranched chain of amino acids.
The number of amino acids present in the chain.
Oligopeptide is loosely used to refer to peptides with 10 to 20
amino acid residues
Polypeptide is a long unbranched chain of amino acids.
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.
Bonds that link amino acids together in peptide chains.
NATURE OF PEPTIDE BOND
The nature of the peptide bond becomes apparent by reconsidering a
chemical reaction previously encountered. General equation for this
reaction is:
PEPTIDE BOND
The end with the free H,N group is called the N-terminal end
written on the left, and the end with the free COO- group is called
the C-terminal end.
AMINO ACID RESIDUE
individual amino acids within a peptide chain
An amino acid residue is the portion of an amino
acid structure that remains, after the release of H2O,
when an amino acid participates in peptide bond
formation as it becomes part of a peptide chain.
AMINO ACID RESIDUE
The abbreviated formula for the tripeptide which contains
the amino acids is Gly-Ala-Ser
Glycine
Alanine
Serine
When we use this abbreviated notation, by convention,
the amino acid at the N-terminal end of the peptide is
always written on the left.
AMINO ACID RESIDUE
Backbone of the peptide
The repeating sequence of peptide bonds and
groups in a peptide
-carbon --CH
R group
The R group side chains are considered substituents on the backbone
rather than part of the backbone.
PEPTIDE NOMENCLATURE
Small peptides are named as a derivative of the C terminal amino
acid that is present.
IUPAC RULES:
1. the C terminal amino acid residue (located at the far right of the
structure) keeps its full amino acid name
2. all of the other amino acid residues have names that end in -yl. The -yl
suffix replaces the -ine or -ic acidic ending of the amino acid name,
except for tryptophan (tryptophyl), cysteine ( cysteinyl). Glutamine
(glutaminyl), and asparagine (asparaginyl)
3. the amino acid naming sequence begins at the N terminal amino acid
residue.
PEPTIDE NOMENCLATURE
Example: Glu-Ser-Ala
Glutamic Acid —>
Serine —>
Alanine —> Alanine
PEPTIDE NOMENCLATURE
Example: Glu-Ser-Ala
Glutamic Acid —> Glutamyl
Serine —> Seryl
Alanine —> Alanine
PEPTIDE NOMENCLATURE
Example: Glu-Ser-Ala
Glutamic Acid —> Glutamyl
Serine —> Seryl
Alanine —> Alanine
glutamylserylalanine
ISOMERIC PEPTIDES
Peptides that contain the same amino acids but in different
order are different molecules with different properties.
Biochemically
Important Small
Peptides
3-8
SMALL PEPTIDES
Small peptides are biochemically active. They function
as hormonal action, neurotransmission, and antioxidant
activity.
SMALL PEPTIDE HORMONES
The two best-known peptide hormones, both produced
by the pituitary gland, are oxytocin and vasopressin.
SMALL PEPTIDE HORMONES
Each hormone is a nonapeptide nine amino acid residues with six of the residues
held in the form of a loop by a disulfide bond formed from the interaction of two
cysteine residues.
SMALL PEPTIDE HORMONES
Oxytocin
regulates uterine contractions and lactation.
Vasopressin
regulates the excretion of water by the kidneys: it also
affects blood pressure.
Another name for vasopressin is antidiuretic hormone
(ADH).
SMALL PEPTIDE NEUROTRANSMITTERS
Enkphalins
are pentapeptide neurotransmitters produced by the
brain itself that bind at receptor sites in the brain to
reduce pain.
The two best-known enkephalins are
Met-enkephalin;
Leu-enkephalin
SMALL PEPTIDE ANTIOXIDANTS
Tripeptide Glutathione (Glu-Cys-Gly)
present in significant concentrations in most cells and is of considerable
physiological importance as a regulator of oxidation-reduction reactions.
Specifically, glutathione functions as an antioxidant, protecting cellular
contents from oxidizing agents such as peroxides and superoxides
General Structural
Characteristics of
Proteins
3-9
Protein Structure: What are the Fundamentals that Define the
General Structural Characteristics of Proteins?
PROTEIN
A naturally occurring, unbranched
polymer composed of amino acid
monomers.
A peptide becomes a protein when it
contains at least 40 amino acids
Polypeptide and protein are used
interchangeably; proteins are
relatively long peptides
Proteins range in size from small (40100 amino acids) to large (over
10,000 amino acids).
Common proteins have 400-500
amino acid residues
PROTEIN STRUCTURE: MONOMERIC VS MULTIMERIC
MONOMERIC PROTEINS
Consists of a single peptide chain
Common in smaller proteins
EXAMPLE: MYOGLOBIN
Myoglobin is a classic example of a
monomeric protein.
It is a single polypeptide chain
protein.
Myoglobin is an oxygen-binding
protein found in muscle tissues.
It is critical for oxygen storage and
utilization in muscle cells.
MULTIMERIC PROTEINS
Comprised more than one peptide
chain
Subunits can be identical or different
Up to 12 subunits observed in
known proteins
EXAMPLE: INSULIN
Insulin, a hormone, is a multimeric
protein
Composed of two subunits with 21
and 30 amino acid residues
PROTEIN CLASSFICATION BY COMPOSITION
SIMPLE PROTEINS
Comprised solely of amino acids residues
May have multiple protein subunits, all containing amino
acids
CONJUGATED PROTEINS
Contains non-amino acid entities in addition to peptide
chains
These non-amino acid components are known as
prosthetic groups
PROTEIN CLASSFICATION BY COMPOSITION
PROSTHETIC GROUPS:
Non-amino acids groups present in a conjugated protein
CONJUGATED PROTEINS
Based on the nature of Conjugated Proteins:
Lipoproteins: Lipid contains prosthetic group
Glycoproteins: Contains carbohydrate groups
Metalloproteins: Contains specific metals, and more.
CLASSIFICICATION OF
CONJULATED PROTEINS
TYPES OF CONJUGATED PROTEINS
PROTEIN STRUCTURE COMPLEXITY
PROSTHETIC GROUPS IN PROTEINS:
Is a non-amino acid group present in a conjugated proteins
Prosthetic groups play crucial roles in the biochemical
functions of conjugated proteins.
PROTEIN STRUCTURE COMPLEXITY:
Proteins exhibit greater three-dimensional complexity
compared to carbohydrates and lipids.
Protein structure is intricate and involves four levels:
primary, secondary, tertiary, and quaternary
LEVELS OF PROTEIN STRUCTURE
Understanding protein structure involves exploring four distinct levels of
organization.
These levels are primary, secondary, tertiary, and quaternary structures
1. Primary Structure:
The primary structure is the linear sequence of amino acids in a protein. It's like the order of letters
in a very long word.
2. Secondary Structure:
The secondary structure involves folding of the protein chain into specific shapes like alpha-helices
or beta-sheets. It's the local folding of segments within the chain.
3. Tertiary Structure:
The tertiary structure refers to the overall three-dimensional shape of a protein. It's the full threedimensional structure of the entire protein.
4. Quaternary Structure:
The quaternary structure involves the interaction between multiple protein subunits (if the protein is
multimeric) and how they come together and function as a complex. It applies to proteins with more
than one polypeptide chain.
3-10
Primary Structure
of Proteins
FREDERICK SANGER: PIONEER IN PROTEIN SEQUENCING
1.Discovery of Insulin's Structure:
In 1953, Frederick Sanger (1918-2013) made a
breakthrough by determining the amino acid
sequence of insulin.
2.Landmark in Biochemistry:
His work unveiled a protein's precise amino acid
sequence, a pivotal moment in biochemistry.
3.Double Nobel Laureate:
Sanger received the Nobel Prize in Chemistry in
1958 for insulin, and in 1980 for nucleic acid
sequencing.
PRIMARY PROTEIN STRUCTURE
Primary structure signifies the
unique amino acid sequence in a
protein, crucial for its function.
Primary structure denotes the
specific order of amino acids linked
by peptide bonds in a protein.
Each protein has a distinct amino
acid sequence, critical for its
biochemical activity.
PRIMARY PROTEIN STRUCTURE
Insulin's 51 amino acid sequence,
decoded by Frederick Sanger in 1953,
was a groundbreaking achievement.
Modern methods automate sequencing,
enabling the knowledge of primary
structures for numerous proteins within
days.
Specific proteins, like the one facilitating
oxygen transport in muscles, have a
defined sequence of 153 amino acids.
PRIMARY PROTEIN STRUCTURE
Refers to the linear sequence of amino
acids in human myoglobin, vital for
understanding the protein's characteristics.
This representation offers the amino acid
sequence but not the three-dimensional
structure.
The sequence, spanning 153 amino acids,
is depicted in a space-efficient "wavy"
pattern.
The actual three-dimensional shape of the
protein is governed by the secondary and
tertiary levels of protein structure.
PRIMARY PROTEIN STRUCTURE
Primary structure is consistent across organisms,
aiding understanding and medical applications.
The primary structure of a protein remains constant
regardless of the organism it is derived from.
Certain proteins, such as insulin, exhibit striking
structural similarity in different animal species.
This similarity is vital for medical treatment,
especially for diabetic patients requiring insulin
injections.
PRIMARY PROTEIN STRUCTURE
Insufficient insulin production in humans leads to
diabetes mellitus, necessitating insulin treatment.
Animal insulin, primarily from cows and pigs, was
used for years due to its similarity to human
insulin.
Human insulin availability increased with genetic
engineering, offering an alternative to animal
insulin.
Genetically engineered bacteria can produce
fully functional human insulin, providing an
effective and accessible option for diabetic
patients
PRIMARY PROTEIN STRUCTURE
Drawing an analogy between protein primary structure and word
formation to highlight sequencing and precision.
Proteins, like words, are structured through specific sequences:
amino acids in proteins and letters in words.
Correct amino acid sequencing is crucial for a protein to be
biochemically active.
Just as words read left to right, amino acids are sequenced
accordingly in protein formulas.
The analogy emphasizes the vast diversity of amino acid
sequences and words, showcasing the remarkable precision of
biological processes in selecting the right sequence.
PRIMARY PROTEIN STRUCTURE
Amino acids in a protein backbone are
connected through peptide linkages,
creating a backbone structure.
The peptide linkages are essentially
planar, with six atoms lying in the same
plane: a-carbon atom, C=O group (first
amino acid), N-H group, and a-carbon
atom (second amino acid).
This planar arrangement contributes to
the characteristic "zigzag" pattern
observed in protein backbones.
PRIMARY PROTEIN STRUCTURE
Peptide linkages exhibit a planar structure, where six atoms lie in
the same plane, restricting rotation.
The planar structure imparts rigidity, hindering rotation around the
C-N bond within the peptide.
Due to restricted rotation, cis-trans isomerism is possible around
the C-N bond, with the trans orientation being more common and
stable.
The O atom of the C=O group and the H atom of the N-H group are
typically positioned trans to each other, contributing to stability.
Peptide bond planarity results in a zigzag arrangement of atoms
within the protein backbone, influencing the overall structure and
stability.
Secondary
Structure of
Protein
3-11
SECONDARY PROTEIN STRUCTURE
Secondary protein structure refers to
the spatial arrangement of the protein
backbone.
Alpha Helix (α-helix) and Beta Pleated
Sheet (β-pleated sheet) are the two
primary forms of secondary structure.
Hydrogen bonding between a carbonyl
oxygen and an amino hydrogen atom in
the peptide linkages is fundamental to
these structures
SECONDARY PROTEIN STRUCTURE
Figure
3-5
illustrates
hydrogen-bonding
between
carbonyl
the
patterns
oxygen
atoms and amino hydrogen
atoms in a protein backbone.
Hydrogen
bonding
occurs
between segments of the same
backbone
backbones,
or
different
influencing
protein's overall structure.
the
THE ALPHA HELIX
Alpha helix is a protein secondary structure characterized by a
coiled spring-like shape formed by a single protein chain.
The alpha helix's coiled configuration is maintained by hydrogen
bonds between N-H and C=O groups.
The twist of the helix forms a right-handed, or clockwise, spiral.
Hydrogen bonds between CO and N-H entities are oriented parallel
to the axis of the helix.
Each hydrogen bond involves a C=O group of one amino acid and
an N-H group of another amino acid, typically four amino acid
residues further along the spiral due to one turn of the spiral
encompassing 3.6 amino acid residues.
THE BETA PLEATED SHEET
A beta pleated sheet is a protein secondary structure where fully
extended protein chain segments, either in the same or different
molecules, are held together by hydrogen bonds.
Hydrogen bonds form between oxygen and hydrogen atoms of
peptide linkages, either within a single folded-back protein chain
(intrachain bonds) or between atoms in different peptide chains
(interchain bonds).
The beta pleated sheet often involves a "U-turn structure" where
several U-turns in the protein chain arrangement are needed to
form the structure.
THE BETA PLEATED SHEET
The term "pleated sheet" comes from
the repeated zigzag pattern in the
structure, contributing to its distinctive
appearance.
Hydrogen bonds between C-O and N-H
entities lie in the plane of the sheet,
while amino acid R groups alternate
between top and bottom positions,
found above and below the plane of the
sheet within a given backbone segment.
UNSATURATED SEGMENTS
Very few proteins have entirely alpha-helix or beta-pleated sheet
structures.
Most proteins exhibit these structures only in certain segments rather
than their entire length.
It is possible for a protein to have both alpha-helix and beta-pleated
sheet structures within different segments of the same molecule.
The adoption of these secondary structures is influenced by the size
of amino acid R groups.
Large R groups can disrupt both alpha-helix and beta-pleated sheet
structures, making them less likely to form in regions with these R
groups.
UNSATURATED SEGMENTS
Regions lacking alpha-helix or beta-pleated sheet
structures.
Common in proteins and distinct from well-defined secondary
structures.
Active research to unveil the roles and significance of
unstructured segments.
Essential in protein functioning, contributing to adaptability
and functionality.
UNSATURATED SEGMENTS
Impart flexibility to proteins, enabling versatile
interactions with different substances.
Rapid adaptation to changing cellular conditions.
Ability to bind with multiple protein partners,
enhancing functional diversity.
Temporary added structure during binding interactions.
Tertiary Structure
of Proteins
3-12
TERTIARY STRUCTURE OF PROTEINS
Tertiary protein structure
The overall three-dimensional shape of a protein that results from the
interactions between amino acid side chains (R groups) that are widely
separated from each other within a peptide chain.
A good analogy for the relationships among the primary, secondary, and
tertiary structures of a protein is that of a telephone cord.
TERTIARY STRUCTURE OF PROTEINS
The primary structure is the long, straight cord. The coiling of the cord
into a helical arrangement gives the secondary structure. The
supercoiling structure arrangement the cord adopts after you hang up
the receiver is the tertiary structure.
TERTIARY STRUCTURE OF PROTEINS
Four types of attractive interactions contribute to the
tertiary structure of a protein
Covalent disulfide bonds
Electrostatic attractions (salt bridges)
Hydrogen bonds
Hydrophobic attractions
All four of these interactions are interactions between amino acid R
groups.
TERTIARY STRUCTURE OF PROTEINS
Disulfide bonds
The strongest of the tertiary-structure interactions. It is the only one with
all the four interactions that involves a covalent bond.
Electrostatic interactions
Also called as salt bridges
Always involve the interaction between an acidic side chain (R group)
and a basic side chain (R group).
TERTIARY STRUCTURE OF PROTEINS
Hydrogen bonds
Can occur between amino acids with polar R groups. They are relatively
weak and are easily disrupted by changes in pH and temperature.
Hydrophobic interactions
Result when two non-polar side chains are close to each other.
Are weaker than hydrogen bonds or electrostatic interactions, they are a
significant force in some proteins because they are so many of them.
TERTIARY STRUCTURE OF PROTEINS
In 1959, a protein tertiary structure was determined
for the first time.
The determination involved myoglobin, a conjugated protein whose
function is oxygen storage in muscle tissue.
TERTIARY STRUCTURE OF PROTEINS
Involves a single peptide chain of
153 amino acids with α helix
segments within the chain.
Quaternary
Structure of
Proteins
3-13
QUATERNARY STRUCTURE OF PROTEINS
Quaternary protein structure
The organization among the various peptide chains in a multimeric
protein.
Quaternary is the highest level of protein organization. It is only found in
multimeric proteins.
QUATERNARY STRUCTURE OF PROTEINS
Multimeric proteins
Contain an even number of
subunits.
The subunits are held together
mainly by hydrophobic interactions
between amino acids R groups.
Protein
Hydrolysis
3-14
PROTEIN HYDROLYSIS
Protein Hydrolysis
Produces free amino acids. This process is the reverse of protein
synthesis, where free amino acids are combined.
Protein Digestion
Is simply enzyme-catalyzed hydrolysis of ingested protein. The
hydrolysis of cellular proteins to amino acids is an ongoing process, as
the body resynthesizes needed molecules and tissue.
Protein
Denaturation
3-15
PROTEIN DENATURATION
Protein Denaturation
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.
Because the biochemical function of a protein depends on its threedimensional shape, the result of denaturation is loss of biochemical
activity. Protein denaturation does not affect the primary structure of a
protein.
PROTEIN DENATURATION
Protein Denaturation
Some proteins lose all
of their threedimensional structural
characteristics upon
denaturation, most
proteins maintain some
three-dimensional
structure.
PROTEIN DENATURATION
Protein Denaturation
For limited denaturation changes, it is possible to find conditions under
which the protein is “refolded”, called renaturation. However, for
extensive denaturation changes, the process is usually irreversible.
Loss of water solubility is a frequent physical consequence of protein
denaturation. The precipitation out of biochemical solution of denature
protein is called coagulation.
PROTEIN DENATURATION
Protein Denaturation
Protein denaturation occurs
when egg white is poured onto a
hot surface. The clear albumin
solution immediately changes in
a white solid lip with a jelly-like
consistency.
PROTEIN DENATURATION
Protein Denaturation
Cooking foods also kills microorganism through protein denaturation.
Ham and bacon can harbor
parasites that cause trichinosis.
Cooking the ham or bacon
denatures parasite protein
PROTEIN DENATURATION
Protein Denaturation
In surgery, heat is often used to seal small blood vessels. This process
is called cauterization. Heat-induced denaturation is used in sterilizing
surgical instruments and in canning foods; bacteria are destroyed when
the heat denatures their protein.
Enzymes, which function as catalysts for almost all body reactions, are
protein. Inactivation of enzymes, through denaturation, can have lethal
effects on body chemistry.
PROTEIN DENATURATION
Protein Denaturation
The effect of ultraviolet radiation from the sun, an ionizing radiation, is
similar to that of heat. Denatured skin proteins cause most of the
problems associated with sunburn.
Alcohol is 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 injection.
PROTEIN DENATURATION
The effectiveness of
a given denaturing
agent depends on
the type of protein
which it is acting on.
Protein
Classification
Based on Shape
3-16
Basis for the classification of proteins
PROTEIN CLASSIFICATION BASED ON SHAPE:
There are 3 main types of proteins:
FIBROUS
GLOBULAR
MEMBRANE
FIBROUS PROTEIN
Molecules have an elongated
shape with one dimension
much longer than the others.
Tend to have simple, regular,
linear structures
Tendency
together
to
aggregate
to
form
macromolecular structures
GLOBULAR PROTEIN
A protein whose molecules
have peptide chains that are
folded into spherical or
globular shapes.
Generally, they are watersoluble substances
GLOBULAR PROTEINS
Globular proteins fold in a way that places the
majority of amino acids with hydrophobic side
chains (non-polar R groups) inside the molecule.
Most of the hydrophilic side chains (polar R
groups) are on the outside of the molecule
MEMBRANE PROTEINS
A protein that is found associated
with a membrane system of a cell
Most of hydrophobic amino acid
side chains originated outward
Tend to be water-insoluble;
usually have fewer hydrophobic
amino acids than globular proteins
FIBROUS PROTEIN VS GLOBULAR PROTEIN
Are generally water-insoluble
Have a single type of secondary
structure
Have structural functions that
provide support and external
protection
Most abundant proteins in the
human body; they exceed the total
mass of globular proteins present.
They are water-soluble (this
enables them to travel through the
blood and other body fluids to sites
where their activity is needed)
Often contain several types of
secondary structure
Involved in metabolic chemistry;
performing functions (eg. catalysis,
transport, & regulation)
SOME COMMON FIBROUS PROTEINS
KERATINS
ELASTINS
COLLAGENS
FIBRIN
MYOSINS
SOME COMMON GLOBULAR PROTEINS
INSULIN
HEMOGLOBIN
TRANSFERRIN
MYOGLOBIN
IMMUNOGLOBULIN
NATURAL SILK
Silkworm silk
Spider silk (web)
These natural silks are made of
Fibroin, which is a fibrous
protein that exists mainly in a
beta pleated sheet form
The great strength and
toughness of these silk fibers,
which exceed those of many
synthetic fibers is related to the
close stacking of the beta sheets
SOME EXAMPLES OF
FIBROUS
PROTEINS
α-keratin
A type of fibrous protein that is particularly
abundant in nature
Found in protective coatings for organisms
Major protein constituent of hair, feathers,
wool, fingernails and toenails, claws, scales,
horns, turtle shells, quills, and hooves.
STRUCTURE OF A TYPICAL α-keratin
Individual molecules form alpha helices.
These helices pair and coil to create coiled coils.
In hair, coiled coils twist to form protofilaments.
Protofilaments group into microfilaments, the core unit of alpha-keratin.
Microfilaments coil further, providing strength.
Attractive forces and disulfide bridges stabilize the structure.
The number of disulfide bridges determines keratin hardness, with "hard"
keratins, like those in horns and nails, having more than their softer counterparts
found in hair, wool, and feathers.
STRUCTURE OF A TYPICAL α-keratin
Collagen
The most abundant of all proteins in humans
(30% of total body protein)
Major
structural
material
in
tendons,
ligaments, blood vessels, and skin
The organic component of teeth and bones
Collagen
The predominant structure feature within collagen molecules is a Triple
Helix formed when three chains of amino acids wrap around each other to
give a ropelike arrangement of polypeptide chains
The dominating presence of two amino acids, Glycine and Proline, are
major driving forces for Triple Helix formation
Collagen
Collagen molecules (triple helices) are very
long, thin, and rigid.
Many such molecules lined up alongside
each other, combine to make collagen
fibrils
Cross-linking between helices gives the
fibrils extra strength. The greater the number
of crosslinks the more rigid the fibril is.
For example:
The stiffening of skin and other tissues
associated with aging is thought to result
from an increasing amount of cross-linking
between collagen molecules.
Also, the process of tanning, which converts
animal hides to leather, involves increasing
the degree of cross-linking.
SOME EXAMPLES OF
GLOBULAR
PROTEINS
Hemoglobin
Transports oxygen from the lungs to tissue
It is a tetramer (four peptide units) with each subunit
also containing a heme group, the entity that binds
oxygen
With 4 heme groups present, a hemoglobin
molecule can transport 4 oxygen molecules at the
same time
It is an iron atom at the center of the heme molecule
that actually interacts with the O2 (oxygen).
Myoglobin
Functions as an oxygen-storage molecule in
muscles
A monomer that contains a single peptide chain
and a heme unit
Only one O2 (oxygen) molecule can be carried
The oxygen stored in the myoglobin molecules serves
as a reserve oxygen source for working muscles
when their demand for oxygen exceeds, which can
supply for the hemoglobin.
Hemoglobin vs. Myoglobin
PROTEIN STRUCTURE AND COLOR OF THE MEAT
The meat the humans eat is composed
of muscle tissue
The major proteins present in these
muscle tissues are Myosin and Actin,
which lie in alternating layers and slide
past
each
contractions.
other
during
muscle
Myosin and Actin
Myosin:
consist of a rodlike coil of two alpha helices (fibrous protein) with two
globular protein heads. It is the “head portions” that interact with actin
Actin:
has two filaments spiraling one another. Each circle represents a monomeric
unit of actin (globular actin). The monomeric actin units associate to form a
long polymer (fibrous actin)
DID YOU KNOW?
The amount of myoglobin present in a muscle
tissue is a major determiner of the color of the
muscle tissue. Since the myoglobin have a red
color when oxygenated and a purple color
when deoxygenated. Thus the heavily worked
muscles have a darker color than seldomly used
muscles.
DID YOU KNOW?
Chicken Leg
Chicken Breast
This difference is related to the amount of myoglobin present in muscle tissue
DID YOU KNOW?
Wild duck & wild geese breast meat
Wild geese
This difference is related to the amount of myoglobin present in muscle tissue
DID YOU KNOW?
Fish are supported by water as they
swim, which reduces the need for
myoglobin oxygen support. Hence, fish
tend to have lighter flesh. Meanwhile,
fish that spend most of their time lying at
the bottom of a body of water have the
lightest (whitest) flesh of all. Salmon
flesh
contains
additional
pigments
(carotenoid astaxanthin) which give its
characteristic “orange-pink” color.
DID YOU KNOW?
When cooked, meat turns brown as the
result of changes in myoglobin structure
caused by the heat. The iron atom in
the heme unit of myoglobin becomes
oxidized.
When the meat is heavily salted with
preservatives (NaCl, NaNO2) eg. ham,
the myoglobin picks up nitrite ions and
its color changes to pink.
QUICK QUIZ!
1. Which of the following statements concerning fibrous and globular proteins are
correct?
a. Fibrous proteins, but not globular proteins are generally water soluble
b. Globular proteins, but not fibrous proteins are generally water soluble
c. Both fibrous and globular proteins are generally water soluble
2. Which of the following proteins has a triple-helix structure?
a. Collagen
b. A-keratin
c. Hemoglobin
QUICK QUIZ!
1. Which of the following statements concerning fibrous and globular proteins are
correct?
a. Fibrous proteins, but not globular proteins are generally water soluble
b. Globular proteins, but not fibrous proteins are generally water soluble
c. Both fibrous and globular proteins are generally water soluble
2. Which of the following proteins has a triple-helix structure?
a. Collagen
b. A-keratin
c. Hemoglobin
Protein
Classification
Based on function
3-17
Basis for the classification of proteins
Protein classification based on function
Proteins play crucial roles in almost all biochemical processes.
The functional versatility of proteins stems from:
(1) their ability to bind small molecules, specifically and strongly to themselves;
(2) their ability to bind other proteins, often other like proteins to form fiber-like
structure;
(3) their ability to bind, and often become integrated into cell membranes.
Several major categories of proteins based on function
1.Catalytic proteins
Proteins are best known for their role as catalysts
Proteins with their role of biochemical catalyst are called enzymes.
Enzymes participate in almost all metabolic reactions that occur in cells.
2. Defense proteins
These proteins are also called Immunoglobulins or antibodies, which are vital
to the function of the immune system of the body.
They bind to foreign substances (eg. bacteria and viruses) to help combat
invasion of the body by foreign particles.
Several major categories of proteins based on function
3. Transport proteins
They bind to particular small biomolecules and transport them to other
locations in the body and then release the small molecules as needed at the
designation location.
The most well-known transport protein is Hemoglobin, which carries oxygen
from the lungs to the other organs and tissues.
Another example of a transport protein is Transferrin, which carries iron from
the liver to the bone marrow.
High and Low density lipoproteins are carriers of cholesterol in the
bloodstream.
Several major categories of proteins based on function
4. Messenger proteins
They transmit signals to coordinate biochemical processes between different
cells, tissues, and organs.
A number of hormones that regulate the body processes are messenger
proteins (eg. Insulin and glucagon)
Human growth hormone (HGH) is another example of a messenger protein.
HGH is a natural hormone your pituitary gland releases that promotes growth in
children, helps maintain normal body structure in adults and plays a role in
metabolism in both children and adults (eg: somatotropin).
Several major categories of proteins based on function
5. Contractile proteins
Necessary for all forms of movement
Muscles are made of filament-like contractile proteins that, in response to
nerve stimuli, undergo conformation changes that involve the contraction and
extension.
Actin and Myosin are examples of contractile proteins
Another example, the long flagella of the sperm cells, which helps them swim,
are made of these contractile proteins.
Several major categories of proteins based on function
6. Structural proteins
Confer stiffness and rigidity to fluid-like biochemical systems
Collagen is a component of cartilage and a-keratin gives mechanical strength and
protective covering to hair, fingernails, hooves, feathers, and some animal shells
7. Transmembrane proteins
Span a cell membrane, which help control the movement of small molecules and
ions through a cell membrane
Many of these proteins give channels through which molecules can enter and exit a
cell; their channels are semi-permeable.
Several major categories of proteins based on function
8. Storage proteins
They store and bind small molecules for future use.
During degradation of hemoglobin, the iron atoms present are released and
become part of Ferritin, which is an iron-storage protein, that saves the iron for
use in the biosynthesis of new hemoglobin molecules
Myoglobin is another example, present in the muscle and stores oxygen which
will later on serve as a source for working muscles.
Several major categories of proteins based on function
9. Regulatory proteins
Often found “embedded” in the exterior surface of cell membranes
Acts as sites at which messenger molecules (such as insulin) can bind and
initiate the effect the the messenger “carries”
Are often the molecules that bind to enzymes (catalytic proteins), thereby
turning them “on” and “off” and thus controlling enzymatic action.
Several major categories of proteins based on function
10. Nutrient proteins
These are particularly important in the early stage of life, from embryo to infant
Casein, which is found in milk; Ovalbumin which is found in egg whites are two
examples of nutrient proteins
The role of milk in nature is to nourish and provide immunological protection for
young mammalians. ¾ of the protein in milk is Casein. More than 50% of the
protein in egg white is Ovalbumin.
Several major categories of proteins based on function
11. Buffer proteins
Part of the system by which the acid-base balance within the body fluids is
maintained.
Within the blood, the protein Hemoglobin has a buffering role in addition to
being an oxygen carrier
12. Fluid-balance proteins
Help maintain fluid-balance between blood and surrounding tissue.
Albumin and Globulin are two-well known fluid balance proteins, found in the
capillary beds of the circulatory system.
QUICK QUIZ!
1. Myoglobin and transferrin are examples of:
a. Transport proteins
b. Structural proteins
c. Storage proteins
2. Enzymes are examples of
a.Catalytic proteins
b. Contractile proteins
c. Regulatory proteins
QUICK QUIZ!
1. Myoglobin and transferrin are examples of:
a. Transport proteins
b. Structural proteins
c. Storage proteins
2. Enzymes are examples of
a. Catalytic proteins
b. Contractile proteins
c. Regulatory proteins
Glycoproteins
3-18
Essential Players in Cell Biology and Beyond
Glycoproteins
Glycoprotein is a protein that contains carbohydrates derivatives in addition to
amino acids.
The carbohydrate content of glycoproteins is variable (from a few percent up to
85%), but it's fixed for any specific glycoprotein.
They include a number of very important substances; two (2) of these, collagen
and immunoglobulins, are considered.
The blood markers of the ABO system are also glycoproteins in which the
carbohydrate content can reach 85%.
TWO (2) IMPORTANT GLYCOPROTEINS
1. COLLAGEN
A fibrous protein
Considered to be a glycoprotein because carbohydrate units are present in
its structure
This structural feature of collagen involves the presence of the Nonstandard
Amino Acids 4-hydroxyproline (5%) and 5-hydroxylysine (1%)--- derivative of
the standard amino acids proline and lysine.
COLLAGEN
COLLAGEN
When collagen is boiled in water, it is converted to the water-soluble protein
gelatin. This process involves both denaturation and hydrolysis. The heat acts
as a denaturant causing the rupture of the hydrogen bonds which supports the
triple helix structure of the collagen.
Meat becomes more tender when cooked because of the conversion of some
collagen to gelatin. Whereas tougher cuts of meat, such as stew meat, need
longer cooking times as they have more cross-linking.
TWO (2) IMPORTANT GLYCOPROTEINS
2. IMMUNOGLOBULINS
Among the most important and interesting soluble proteins in the human body.
A type of glycoprotein produced by an organism as a protective response to
the invasion of microorganisms or foreign molecules.
Different classes of immunoglobulins, identified by differing carbohydrate
content and molecular mass, exist.
IMMUNOGLOBULINS
Serve as Antibodies to combat invasion of the body by Antigens.
Antigen: foreign substance (eg. Bacteria and virus) that invades the human
body
Antibody: biochemical molecule that counteracts a specific antigen.
The immune system of the human body has the capability to produce
immunoglobulins that respond to millions to several million of different antigens.
IMMUNOGLOBULINS
All immunoglobulin molecules share a common basic structure, including:
1. 4 polypeptide chains are present: 2 identical heavy (H) chains and 2 identical
light (L) chains
2. The H chains, which usually contain 400-500 amino acid residues, are
approximately twice as long as the L chains.
3. Both the H and L chains have constant and variable regions.
4. The carbohydrate content of various immunoglobulins varies from 1% to 12% by mass.
5. The secondary and tertiary structures are similar for all immunoglobulins.
IMMUNOGLOBULINS
The interaction of an immunoglobulin
molecule with an antigen occurs at the
“tips” or upper most part of the Y
structure.
These
tips
are
variable-
composition regions of the immunoglobulin
structure. It is here that the antigen binds
specifically, and it is here that the amino
acid
sequence
differs
immunoglobulin to another.
from
one
IMMUNOGLOBULINS
Each Immunoglobulin has 2
identical active sites and can bind
to two molecules of antigen it is
“designed” for. The action of many
such immunoglobulins of a given
type in concert with each other
creates an “antigen-antibody”
complex that precipitates from
solution.
SCHEMATIC DIAGRAM OF AN IMMUNOGLOBULIN
QUICK QUIZ!
1. Which of the following statements concerning basic immunoglobulin structure is
incorrect?
a. Four identical polypeptide chains are present
b. Two “heavy” and two “light” polypeptide chains are present
c. Two identical active sites are present
2. Which of the following statements about antibodies is correct?
a. foreign substances that invade the human body
b. substances that counteract the effects of antigens
c. substances that counteract the effects of immunoglobulins
QUICK QUIZ!
1. Which of the following statements concerning basic immunoglobulin structure is
incorrect?
a. Four identical polypeptide chains are present
b. Two “heavy” and two “light” polypeptide chains are present
c. Two identical active sites are present
2. Which of the following statements about antibodies is correct?
a. foreign substances that invade the human body
b. substances that counteract the effects of antigens
c. substances that counteract the effects of immunoglobulins
Lipoproteins
3-19
Lipids + Proteins = Lipoproteins?
LIPOPROTEINS
Lipoprotein is a conjugated protein that contains lipids in addition to amino
acids.
The major function of these proteins is to help suspend lipids and transport
them through the bloodstream.
Lipids, in general, are insoluble in blood (aqueous medium) because of their
nonpolar structure.
PLASMA LIPOPROTEIN
A lipoprotein that is involved in the transport system for lipids in the bloodstream.
They have a spherical structure that involves a central core of lipid material
(triacylglycerols and cholesterol esters) surrounded by a shell (membrane
structure) of phospholipids, cholesterol, and 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.
STRUCUTURE OF A PLASMA LIPOPROTEIN
PLASMA LIPOPROTEIN
PLASMA LIPOPROTEIN
Spherical lipoproteins have a polar exterior.
The
outer
phospholipid
surface
contains
polar
heads,
cholesterol
polar
regions, and membrane protein portions.
Nonpolar conditions inside the structures,
mainly
comprising
fatty
acid
esters
of
cholesterol.
The polar exterior and nonpolar interior
structure
enables
compatibility
aqueous-based blood medium.
with
the
4 Major classes of Plasma Lipoproteins:
1.Chylomicrons
Their function is to transport triacylglycerols from the intestine to the liver and
to adipose tissue.
2. Very-low-density lipoproteins (VLDLs)
Their function is to transport triacylglycerols synthesized in the liver to adipose
tissue.
4 Major classes of Plasma Lipoproteins:
3. Low-density lipoproteins (LDLs)
Their function is to transport cholesterol synthesized in the liver cells
throughout the body
4. High-density lipoproteins (HDLs)
Their function is to collect excess cholesterol from body tissues and transport
it back to the liver for degradation to bile acids.
Take note!
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 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.
Thank you!