BSN

BIOCHEMISTRY
Chapter III: Proteins
ROLINA M. CABALLERO, RN
 Learning Outcome
3.1 Characterize a protein in terms
of the subunits present in its
polymeric structure and in term of
the elements that are present.
3.1 Characteristics of Protein
• Protein: Naturally-occurring, unbranched polymer in
which the monomer units are amino acids
• Most abundant substance in cells after water
– Account for about 15% of a cell’s overall mass
• Elemental composition - Carbon (C), hydrogen (H),
nitrogen (N), oxygen (O), and sulfur (S)
– Average nitrogen content is 15.4% by mass
• Contain iron (Fe), phosphorus (P), and other metals in
certain specialized proteins
 Learning Outcome

3.2 Be able to draw a generalized structure

for an α- amino acid and be able to classify
α- amino acids into four categories based in
structures and polarity of their side chain.
 3.2 Amino Acids: The Building Blocks for Proteins
• Contain both an amino (—NH2) and a carboxyl
(—COOH) group
– α-amino acids: Amino acids in which the amino
group and the carboxyl group are attached to the
α-carbon atom
• Side chains (R) - Vary in size, shape, charge,
acidity, functional groups present,
hydrogen-bonding ability, and chemical reactivity
– >700 amino acids are known
The general structural formula for an a-amino acid
 Standard Amino Acids
• 20 α-amino acids normally found in proteins
• Divided based on the properties of R-groups
– Nonpolar amino acids: Contain one amino group,
one carboxyl group, and a nonpolar side chain
• Hydrophobic - Not attracted to water molecules
• Found in the interior of proteins, where there is no
polarity
– Polar amino acids - Hydrophilic
• Types - Polar neutral, polar acidic, and polar basic
 Polar Amino Acids
• Polar neutral: Contain polar but neutral side chains
– Six amino acids belong to this category
• Polar acidic: Contain a carboxyl group as part of the
side chains
– Two amino acids belong to this category
• Polar basic: Contain an amino group as part of the side
chain
– Three amino acids belong to this category
 Nomenclature
• Three-letter abbreviations are used for naming standard
amino acids
– Abbreviations are the first three letters of the amino acid’s
name
• Exceptions: Isoleucine (Ile), tryptophan (Trp),
asparagine (Asn), and glutamine (Gln)
– One-letter symbols - Used for comparing amino acid
sequences of proteins
• Usually the first letter of the name
• When more than one amino acid has the same letter,
the most abundant amino acid gets the 1st letter
Table 20-1 The 20 Standard Amino Acids, Grouped According to
Side-Chain Polarity
 Learning Outcomes

3.3 Be familiar with the concepts

of essential amino acids,
complete, incomplete, and
complementary dietary proteins
and limiting amino acids.
 3.3 Essential Amino Acids

• Standard amino acids needed for protein synthesis and

must be obtained from dietary sources
– Types of dietary proteins - Complete, incomplete,
and complementary
A complete dietary protein is a protein that contains all of
the essential amino acids in the same relative amounts in
which the body needs them.
● may or may not contain all of the nonessential amino
acids.

An incomplete dietary protein is a protein that does not

contain adequate amounts, relative to the body’s needs,
of one or more of the essential amino acids.
A limiting amino acid is an essential amino acid that
is missing, or present in inadequate amounts, in an
incomplete dietary protein.

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.
Protein Energy Malnutrition

● is a common childhood disorder and is primarily

caused by deficiency of energy, protein, and
micronutrients.

● Underweight (low body weight compared with

healthy peers), stunting (poor linear growth),
wasting (acute weight loss), or edematous
malnutrition (kwashiorkor).
https://www.sciencedirect.com/topics/medicine-and-dentistry/protein-calorie-malnutrition
 In children, chronic primary PEM has two common
forms:
● Marasmus (also known as the dry style of PEM)
causes weight loss and depletion of fat and muscle.

● Kwashiorkor (also known as the wet, swollen, or

unhealthy form) may be a risk when premature
abandonment of breastfeeding, which generally
happens once a younger sibling, is born, displacing
the older child from the breast.
 Learning Outcome

3.4 Know the handedness pattern for

standard amino acids and how handedness is
designated using Fischer projection formulas
for amino acids.
3.4 Chirality and Amino Acids
• Amino acids found in nature and in proteins are
ʟ isomers
– Exceptions: Some bacteria
– Monosaccharides prefer ᴅ isomers
• Rules for drawing Fischer projection formulas for
amino acid structures
– —COOH group is placed at the top of the projection
formula
– R group is placed at the bottom, positions
the carbon chain vertically
– —NH2 group is placed in a horizontal
position
– NH2 on the left - ʟ isomer
– NH2 on the right - ᴅ isomer
Fischer projection formulas for both enantiomers
of the amino acids alanine and serine
 Learning Outcome

3.5 Know the chemical basis

for the zwitterion structure
adopted by amino acids;
know how zwitterion
structure changes as a
function of solution pH
 3.5 Acid-Base Properties of Amino Acids
• In pure form, amino acids are white crystalline solids
– Decompose before they melt
• Not very soluble in water
• α-amino acids exist as zwitterions in solution and in
solid state
– Zwitterions: Molecules with positive charge on
one atom and negative charge on another, but
have no net charge
 • Carboxyl groups give up protons to
produce a negatively charged species
• Amino groups accept protons to produce a
positively charged species
• Amino acid forms in solution
– Zwitterions, positive ion, and negative ion
– Equilibrium shifts with change in pH
In an acidic solution, the zwitterion accepts a
proton (H+) to form a positively charged ion.
● The side chain (R group) of an amino acid
remains unchanged in solution as the pH is
varied for neutral amino acids.

● For acidic or basic, the side chain can also

acquire a charge because it contains an
amino or a carboxyl group that can,
respectively, gain or lose a proton
 Isoelectric Point (pI)

• pH at which an amino acid exists in its zwitterion form

– Carries zero net charge
• Different amino acids have different isoelectric points
 Learning Outcome

3.6 Be familiar with the unique

ability of the amino acid cysteine
to form disulfide covalent bonds.
 Cysteine: A Chemically Unique Amino Acid

● Standard amino acid that has a side chain that

contains a sulfhydryl group (—SH group)
● Sulfhydryl group imparts cysteine a unique
chemical property
● Cysteine, in the presence of mild oxidizing
agents, dimerizes to form a cystine molecule
● Cystine contains two cysteine residues linked
via a covalent disulfide bond
 Learning Outcome

3.7 Be familiar with the terminology peptide,

peptide bond, and amino acid residue; be
able to draw structural formulas for small
peptides and to name using IUPAC rules;
know how the concepts of isomerism relates
to the sequence of amino acids in a peptide.
 3.7 Peptides
Nature of the Peptide Bond
• Under proper conditions, amino acids can bond together to
produce a peptide chain
– Peptide: Unbranched chain of amino acids
• Dipeptide - Compound containing two amino acids
• Oligopeptide - Peptide with 10 to 20 amino acid
residues
• Polypeptide: Long unbranched chain of amino acids
❏ Two amino acids can combine in a similar
way—the carboxyl group of one amino acid
interacts with the amino group of the other
amino acid.

❏ The products are a molecule of water and a

molecule containing the two amino acids linked
by an amide bond.
Removal of the elements of water from the reacting
carboxyl and amino groups and the ensuing formation of
the amide bond
 Nature of the Peptide Bond

• Length of the amino acid chain can vary from a few

amino acids to hundreds of amino acids
– Peptide bonds: Covalent bonds between amino
acids in a peptide
• Every peptide has an N-terminal end and a
C-terminal end
● In all peptides, long or short, the amino acid at one end
of the amino acid sequence has a free H3N + group,
and the amino acid at the other end of the sequence
has a free COO− group.

● N-terminal end, free H3N + group

● C-terminal end. free COO− group
The individual amino acids within a peptide chain are
called amino acid residues.

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
The repeating sequence of peptide bonds and a-carbon
CH groups in a peptide is referred to as the backbone of
the peptide
Converting an Abbreviated Peptide Formula to a
Structural Peptide Formula Draw the structural formula
for the tripeptide Ala–Gly–Val.
Step 1: The N-terminal end of the peptide involves
alanine. Its structure is written first
Step 2: The structure of glycine is written to the right of
the alanine structure, and a peptide bond is formed
between the two amino acids by removing the elements
of H2O and bonding the N of glycine to the carboxyl C of
alanine.
Step 3: To the right of the just-formed dipeptide, draw the
structure of valine. Then repeat Step 2 to form the
desired tripeptide.
 Peptide Nomenclature
Small peptides are named as derivatives of the
C-terminal amino acid that is present. The IUPAC rules
for doing this are:

Rule 1: The C-terminal amino acid residue (located at

the far right of the structure) keeps its full amino acid
name.
Ex: Glu–Ser–Ala
alanine remains alanine
 Peptide Nomenclature
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
tryptophan (tryptophyl), cysteine (cysteinyl), glutamine
(glutaminyl), and asparagine (asparaginyl).

Glutamic acid becomes glutamyl

Serine becomes seryl
Peptide Nomenclature
Rule 3: The amino acid naming sequence begins at
the N-terminal amino acid residue

glutamylserylalanine
 Isomeric Peptides

• Peptides that contain the same amino acids but present

in different order are different molecules (constitutional
isomers) with different properties
– For example, two different dipeptides can be formed
from one molecule of alanine and glycine
• Number of possible isomeric peptides increases rapidly
as the length of the peptide chain increases
Learning Outcome

3.8 Know the names and characteristics of

several biochemically important small
peptides.
 3.8 Biochemically Important Small Peptides
Small Peptide Hormones
• Best-known peptide hormones - Oxytocin and
vasopressin
– Produced by the pituitary gland
– Hormones are nonapeptides (nine amino acid
residues)
• Have 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 Neurotransmitters

• Enkephalins are pentapeptide

neurotransmitters produced by the brain
– Bind receptor sites in the brain to reduce pain
• Best-known enkephalins
– Met-enkephalin: Tyr–Gly–Gly–Phe–Met
– Leu-enkephalin: Tyr–Gly–Gly–Phe–Leu
 Small Peptide Antioxidant

• Glutathione (Glu–Cys–Gly) - Tripeptide

present in high levels in most cells
– Regulates oxidation–reduction reactions
– Antioxidant that protects cellular contents from
oxidizing agents such as peroxides and
superoxides
– Unusual structural feature - Glu is bonded to Cys
through the side-chain carboxyl group
 Learning Outcome

3.9 Distinguish between the terms protein and

polypeptide, between the terms monomeric
proteins and polymeric protein, and between the
terms simple protein and conjugated protein.
 3.9 General Structural Characteristics of Proteins
Protein
• General definition - Naturally-occurring, unbranched
polymer in which the monomer units are amino acids
• Specific definition - Peptide in which at least 40 amino
acid residues are present
– The terms polypeptide and protein are used
interchangeably to describe a protein
– Several proteins have >10,000 amino acid residues
 – Common proteins contain 400–500 amino acid
residues
– Small proteins contain 40–100 amino acid residues
• More than one polypeptide chain may be present
in a protein
– Monomeric: Protein which contains one polypeptide
chain
– Multimeric: Protein which contains two or more
polypeptide chains
Protein Classification Based on Chemical Composition
• Simple protein: Protein in which only amino acid
residues are present
– More than one protein subunit may be present
• Conjugated protein: Protein that has one or more
non-amino-acid entities (prosthetic groups) present in
its structure
– One or more polypeptide chains may be present
– Non-amino-acid components may be organic or
inorganic
– May be classified further based on the nature of
prosthetic group(s) present
• Lipoprotein contains lipid prosthetic groups
• Glycoprotein contains carbohydrate groups
• Metalloprotein contains a specific metal as its
prosthetic group
 Learning Outcome

3.10 Understand what is meant by the

term primary protein structure and how
such structure is specified.
3.10 Primary Structure of Proteins

Figure 20.4 -
Primary Structure
of a Human
Myoglobin
• Primary structure of a specific protein is the
same within the organism
– Structures of certain proteins are similar among
different species of animals
• Example: Insulin from pigs, cows, sheep, and humans
are similar but not identical
• Amino acids are linked to each other by peptide
linkages
Differences in Animal and Human Insulin
• Immunological reactions gradually increase
over time because animal insulin is foreign to
the human body
• Human insulin produced from genetically
engineered bacteria is available
Important Points Regarding Peptide Bond Geometry

• Peptide linkages are essentially planar

– For two amino acids linked through a peptide
bond, six atoms lie in the same plane
– Planar peptide linkage structure has considerable
rigidity, therefore rotation of groups about the
C—N bond is hindered
• Cis–trans isomerism is possible about C—N bond
• Trans isomer is the preferred orientation
Learning Outcome
3.12 Distinguish tertiary
protein structure from
secondary protein
structure in terms of the
types of attractive forces
that contribute to the
structure
Tertiary protein structure is 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.
Interactions Responsible for Tertiary Structure

(1) covalent disulfide bonds,

(2) electrostatic attractions (salt bridges)
(3) hydrogen bonds, and
(4) hydrophobic attractions
Tertiary-structure interactions involve the R groups of
amino acids;
Secondary-structure interactions involve the peptide
linkages between amino acid residues.

Disulfide bonds, the strongest of the tertiary-structure

interactions, result from the SH groups of two cysteine
residues reacting with each other to form a covalent
disulfide bond
Electrostatic interactions, also called salt bridges,
always involve the interaction between an acidic
side chain (R group) and a basic side chain (R
group).
Hydrogen bonds can occur between amino acids
with polar R groups. Are relatively weak and are
easily disrupted by changes in pH and
temperature.
Hydrophobic interactions result when two nonpolar
side chains are close to each other.
The four types of stabilizing interactions between amino acid
R groups that contribute to the tertiary structure of a protein
 Four of the stabilizing interactions that contribute to tertiary protein
structure in the context of a single peptide chain
Learning Outcome

3.13 Know the necessary requirements for

protein quaternary structure.
Quaternary protein structure is the organization among the
various peptide subunits 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 alpha

subunits and two identical beta subunits. Each subunit
enfolds a heme group, the site where oxygen binds to the
protein.
 CLINICAL MANIFESTATION
Prion diseases are a group of rare neurodegenerative
disorders that can affect both humans and animals.

They’re caused by abnormally folded proteins in the

brain, particularly the misfolding of prion proteins/
cellular glycoprotein (PrP).

This leads to a progressive decline in brain function,

involving changes in memory, behavior, and
movement. Eventually, prion diseases are fatal.
Creutzfeldt-Jakob Disease (CJD), which reportedly
affects around one person per million per population
per year
Learning Outcome

3.14 Know the condition necessary

for and the produced when proteins
are hydrolyzed.
 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

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
The complete hydrolysis of the tripeptide Ala–Gly–Cys
under acidic conditions
Learning Outcome
3.15 Know what occurs
structurally when a protein is
denatured; know the identity of
common protein –denaturing
agents.
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

The result of denaturation is loss of biochemical

activity.
Renaturation is the restoration process for limited
denaturation changes, it is possible to find
conditions under which the effects of denaturation can
be reversed

Coagulation is the precipitation out of biochemical

solution of denatured protein
the change in the structure of protein (from a liquid
form to solid or a thicker liquid) brought about by heat,
mechanical action or acids.
• Example:
• Egg white is a concentrated solution of
protein albumin, which forms a jelly when heated
• Cooking denatures proteins
– Makes it easy for enzymes in our body to
hydrolyze/digest protein
– Kills microorganisms by denaturation of proteins
• A fever of above 106°F is dangerous
– Denatures and inactivates the body’s enzymes, which
function as catalysts
Learning Outcome

3.16 Know the basis for the classification

of proteins as fibrous or globular; know the
structural characteristics and biochemical
functions for the proteins α- Keratin,
collagen, hemoglobin, and myoglobin.
 Protein Classification Based on Shape
• Fibrous proteins: Protein molecules with elongated
shape
– One dimension is much longer than the others
– Generally insoluble in water
– Have a single type of secondary structure
– Tend to have simple, regular, and linear structures
– Aggregate together to form macromolecular
structures
• Example: Hair, nails, etc
• Globular proteins: Protein molecules with
peptide chains folded into spherical or globular
shapes
– Water soluble substances - Hydrophobic amino acid
residues are in the protein core
• Membrane proteins: Proteins associated with
cell membranes
– Insoluble in water - Hydrophobic amino acid residues
are on the surface
 Fibrous Proteins: α-Keratin
• Provide protective coating for organisms
• Major protein constituent of hair, feather, nails, horns,
and turtle shells
• Mainly made of hydrophobic amino acid residues
• Individual molecules are almost wholly α helical
– Pairs of these helices twine about one another to
produce a coiled coil
– Coiling at higher levels produces the strength
associated with α-keratin-containing proteins
Fibrous Proteins: Collagen
• Most abundant protein in humans (30% of total
body protein)
• Major structural material in tendons, ligaments,
blood vessels, and skin
• Organic component of bones and teeth
• Predominant structure - Triple-helix
– Glycine and proline help maintain the structure of the
triple-helix
Globular Proteins: Hemoglobin

• An oxygen-carrier molecule in blood

– Transports oxygen from lungs to tissues
• Tetramer (four polypeptide chains)
– Each subunit contains a heme group
• One molecule can transport up to four oxygen
molecules at time
• Iron atom in heme interacts with oxygen
Globular Proteins: Myoglobin
• Oxygen-storage molecule in muscles
• Monomer
– Consists of a single peptide chain and one heme unit
– One molecule carries one O2 molecule
• Has a higher affinity for oxygen than hemoglobin
• Oxygen stored in myoglobin molecules serves
as a reserve source for working muscles when
oxygen demand exceeds its supply
Learning Outcome

3.17 Be able to classify proteins in

terms of the functions that they
exhibit in biological processes.
 3.17 Protein Classification Based on Function
• Proteins play crucial roles in biochemical processes
• Diversity of functions exhibited by proteins exceeds the
role of other biochemical molecules
• Functional versatility of proteins stems from their ability
to:
– Bind small molecules specifically and strongly
– Bind other proteins and form fiber-like structures
– Integrate into cell membranes
• Catalytic proteins are known for their role as catalysts
– Almost every chemical reaction in the body is driven
by an enzyme
• Defense proteins are central to functioning of the body’s
immune system
– Known as immunoglobulins or antibodies
• Transport proteins bind to small biomolecules, transport
them to other locations in the body, and release them as
needed
• Messenger proteins transmit signals to coordinate
biochemical processes between different cells, tissues,
and organs
– Examples: Insulin, glucagon, and human growth
hormone
• Contractile proteins are necessary for all forms of
movement
– Examples: Actin and myosin
– Human reproduction depends on the movement of
sperm, which is possible because of contractile
proteins
• Structural proteins confer stiffness and rigidity
– Collagen is a component of cartilage
– α-keratin gives mechanical strength and protective
covering to hair, nails, feathers, and hooves
• Transmembrane proteins control the movement of small
molecules and ions through the cell membrane
– Have channels to help molecules enter and exit the
cell
– Selective, allow passage of only one type of molecule
or ion
• Storage proteins bind (and store) small molecules
– Ferritin - Iron-storage protein which saves iron for use
in the biosynthesis of new hemoglobin molecules
– Myoglobin - Oxygen-storage protein present in
muscle
• Regulatory proteins are found embedded in the exterior
surface of cell membranes
– Act as sites for receptor molecules
– Bind to enzymes (catalytic proteins) and control
enzymatic action
• Nutrient proteins are important in the early stages of life,
from embryo to infant
– Examples: Casein (found in milk) and ovalbumin
(found in egg white)
• Milk provides immunological protection for
mammalian young
• Buffer proteins are part of the system by which the
acid–base balance within body fluids is maintained
• Fluid-balance proteins maintain fluid balance between
blood and surrounding tissue
 Learning Outcome
3.18 Understand why
collagen is classified as
glycoprotein; be familiar with
the general structural
characteristics of an
immunoglobulin; know the
relationship between the
terms antigen and antibody.
 3.18 Glycoproteins
• Contain carbohydrates or carbohydrate derivatives in addition
to amino acids
– Examples: Proteins in cell membrane and blood group
markers of the ABO system
• Collagen
– Structural feature - 4-hydroxyproline (5%) and
5-hydroxylysine (1%)
– Carbohydrate units are attached by glycosidic linkages to
collagen at its 5-hydroxylysine residues
• Direct the assembly of collagen triple helices into
collagen fibrils
Immunoglobulins
• Produced as a protective response to the invasion of
microorganisms or foreign molecules
• Serve as antibodies to combat invasion of the body by
antigens
– Antigen: Foreign substance, such as a bacterium or
virus, that invades the human body
– Antibody: Biochemical molecule that counteracts a
specific antigen
Immunoglobulins
• Bonding of an antigen to variable regions of
immunoglobulins occurs through hydrophobic
interactions, dipole–dipole interactions, and
hydrogen bonds
Learning Outcome
3.19 Be familiar with
the four major
classes of plasma
lipoproteins in terms
of biological function
and density
characteristics.
 3.19 Lipoproteins
• Conjugated proteins that contain lipids and amino
acids
• Help suspend lipids and transport them through the
bloodstream
• Classes of plasma lipoproteins
– Chylomicrons - Transport dietary triacylglycerols
from intestine to the liver and to adipose tissue
– Very-low-density lipoproteins (VLDL) -
Transport triacylglycerols synthesized in the
liver to adipose tissue
– Low-density lipoproteins (LDL) - Transport
cholesterol synthesized in the liver to cells
throughout the body
– High-density lipoproteins (HDL) - Collect
excess cholesterol from body tissues and
transport it back to the liver for degradation to
bile acids