PROTEINS (MIDTERM)

CHARACTERISTICS OF PROTEIN

Proteins - are the most abundant substances in nearly all cells— they account for about 15% of a cell’s
overall mass and for almost half of a cell’s dry mass.

 Protein is a naturally occurring, unbranched polymer in which the monomer units are amino
acids.
 All proteins contain the elements carbon, hydrogen, oxygen, and nitrogen; most also contain
sulfur.
 The presence of nitrogen in proteins sets them apart from carbohydrates and lipids, which most
often do not contain nitrogen.
 The average nitrogen content of proteins is 15.4% by mass.
 Phosphorus and iron, are essential constituents of certain specialized proteins.
 Casein, the main protein of milk, contains phosphorus, an element very important in the diet of
infants and children.
 Hemoglobin, the oxygen-transporting protein of blood, contains iron

INVOLVEMENT OF PROTEIN IN HUMAN BODY

 INVOLVE IN METABOLIC REACTION, AND CATALYST..
 ALSO ACT ANTIBODIES DEFENSE MECHANISM….
 INVOLVE IN TRANSMISSION OF NERVE IMPULSE AND MUSCLE CONTACTION…
 COMPONENTS OF SKIN HAIR AND NAILS AND CONNECTING AND SUPPORTING TISSUE..

AMINO ACIDS: The Building Blocks for Proteins

 Amino acid is an organic compound that contains both an amino (---NH2) group and a carboxyl
(---COOH) group.
 Always alpha -amino acids.
 Alpha-amino acid is an amino acid in which the amino group and the carboxyl group are
attached to the a-carbon atom.
 amino acid Side chain - The R group present in an a-amino acid
o Side chains vary in size, shape, charge, acidity, functional groups present, hydrogen-
bonding ability, and chemical reactivity
 Standard amino acid is one of the 20 a-amino acids normally found in proteins.

FOUR CATEGORIES

 (1) Nonpolar amino acids - an amino acid that contains one amino group, one carboxyl group,
and a nonpolar side chain.
o When incorporated into a protein, such amino acids are hydrophobic
 They are not attracted to water molecules.
 They are generally found in the interior of proteins, where there is limited
contact with water.
  There are nine nonpolar amino acids: Glycine, Alanine, Valine, Leucine,
Isoleucine, Proline, Phenylalanine, Methionine, Tryptophan
o Tryptophan is a borderline member of this group because water can weakly interact
through hydrogen bonding with the NH ring location on tryptophan’s side-chain ring
structure.
o Within a protein, such amino acids are considered to be hydrophilic

 (2) polar neutral amino acids - is an amino acid that contains one amino group, one carboxyl
group, and a side chain that is polar but neutral.
o In solution at physiological pH, the side chain of a polar neutral amino acid is neither
acidic nor basic.
o EXAMPLE: Serine, Cysteine,Threonine, Asparagine, Glutamine, Tyrosine,
o These amino acids are more soluble in water than the nonpolar amino acids as, in each
case, the R group present can hydrogen-bond to water. 

 (3) polar acidic amino acids- is an amino acid that contains one amino group and two carboxyl
groups, the second carboxyl group being part of the side chain.
o In solution at physiological pH, the side chain of a polar acidic amino acid bears a
negative charge; the side-chain carboxyl group has lost its acidic hydrogen atom.
o There are two polar acidic amino acids: aspartic acid and glutamic acid.
o EXAMPLE: Aspartic acid, Glutamic acid

 (4) polar basic amino acids- is an amino acid that contains two amino groups and one carboxyl
group, the second amino group being part of the side chain
o In 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
o There are three polar basic amino acids: Histidine, Lysine, Arginine

 All of the standard amino acids are necessary constituents of human proteins.
 Adequate amounts of 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. These amino acids, which are called essential amino acids, must be obtained from
dietary protein.

ESSENTIAL AMINO ACIDS

 Essential amino acid is a 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.
 The Essential Amino Acids : arginine* methionine,
histidine ,phenylalanine ,isoleucine ,threonine, leucine, tryptophan , lysine, valine *
 ARGININE is required for growth in children but is not an essential amino acid for adults
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.

 A complete dietary protein may or may not contain all of the nonessential amino acids.

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.

 Associated with the term incomplete dietary protein is the term limiting amino acid.
 LIMITING AMINO ACID is an essential amino acid that is missing, or present in inadequate
amounts, in an incomplete dietary protein.

 Protein from animal sources is usually complete dietary protein

 CASEIN from milk and proteins found in meat, fish, and eggs are complete dietary proteins.
 Incomplete dietary protein that comes from animal sources. - GELATIN, a protein in which
tryptophan is the limiting amino acid.
 With plant proteins, three amino acids are often limiting: lysine (wheat, rice, oats, and corn),
methionine (beans and peas), and tryptophan (corn and beans).
o Note that both corn and beans have two limiting amino acids.
 Soy is the only common plant protein that is a complete 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.
 Rice by itself is an incomplete dietary protein, as is beans.
 A serving of rice and beans provides all of the essential amino acids by protein complementation

CHIRALITY AND AMINO ACIDS

 GLYCINE, the simplest of the standard amino acids, is achiral. All of the other standard amino
acids are chiral.
 Fischer projection formulas (Section 18-6) for amino acid structures follow.
 1. The -COOH group is put at the top of the projection formula, the R group at the bottom.
This positions the carbon chain vertically.
 2. The -NH2 group is in a horizontal position. Positioning it on the left denotes the l isomer,
and positioning it on the right denotes the d isomer.

Amphoteric can react with acid and base due to the presence of carbonyl group…

ACID–BASE PROPERTIES OF AMINO ACIDS

 Also, most amino acids are not very soluble in water because of strong intermolecular forces
within their crystal structures. Such properties are those often exhibited by compounds in
which charged species are present.
 Studies of amino acids confirm that they are charged species both in the solid state and in
solution
 Both an acidic group (--COOH) and a basic group (--NH2) are present on the same carbon in
an a-amino acid. 
  In neutral solution, amino groups have a tendency to accept protons (H+), producing a
positively charged species: --- NH2 + H  NH3+
 Consistent with the behavior of these groups, in neutral solution, the --COOH group of an
amino acid donates a proton to the !NH2 of the same amino acid. We can characterize this
behavior as an internal acid–base reaction.
 ZWITTERION, from the German term meaning “double ion.” A zwitterion is a molecule that
has a positive charge on one atom and a negative charge on another atom, but which has
no net charge.
o Note that the net charge on a zwitterion is zero even though parts of the molecule
carry charges. In solution and also in the solid state, a-amino acids exist as
zwitterions. 
 Zwitterion structure changes when the pH of a solution containing an amino acid is
changed from neutral either to acidic (low pH) by adding an acid such as HCl or to basic
(high pH) by adding a base such as NaOH.
o In an acidic solution, the zwitterion accepts a proton (H+) to form a positively
charged ion.
o In basic solution, the --NH3 of the zwitterion loses a proton, and a negatively
charged species is formed.
 The three species are actually in equilibrium with each other, and the equilibrium shifts with
pH change
o The three species are actually in equilibrium with each other, and the equilibrium
shifts with pH change.

ISOELECTRIC POINTS

 An important pH value, relative to the various forms an amino acid can have in solution, is the
pH at which it exists primarily in its zwitterion form, that is, its neutral form (no net charge). This
pH value is known as the isoelectric point for the amino acid.
 AN ISOELECTRIC POINT is the pH at which an amino acid exists primarily in its zwitterion form.
 At the isoelectric point, almost all amino acid molecules in a solution (more than 99%) are
present in their zwitterion form.
 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.
Isoelectric Points for the 20 Amino Acids Commonly Found in Proteins

alanine 6.01 glycine 5.97 proline 6.48

arginine 10.76 histidine 7.59 serine 5.68

asparagine 5.41 isoleucine 6.02 threonine 5.87

aspartic acid 2.77 leucine 5.98 tryptophan 5.88

cysteine 5.07 lysine 9.74 tyrosine 5.66

glutamic acid 3.22 methionine 5.74 valine 5.97

glutamine 5.65 phenylalanine 5.48

CYSTEINE: A CHEMICALLY UNIQUE AMINO ACID

 CYSTEINE is the only standard amino acid that has a side chain that contains a sulfhydryl group
(--SH group)
 The presence of this sulfhydryl group imparts to cysteine a chemical property that is unique
among the standard amino acids.
 Cysteine, in the presence of mild oxidizing agents, readily dimerizes, that is, reacts with another
cysteine molecule to form a cystine molecule. (A dimer is a molecule that is made up of two like
subunits.)
 In cystine, the two cysteine residues are linked via a covalent disulfide bond
 The covalent disulfide bond of cystine is readily broken, using reducing agents, to regenerate
two cysteine molecules. This oxidation–reduction behavior involving sulfhydryl groups and
disulfide bonds when the reactions of thiols were considered.

PEPTIDES

 A peptide is an unbranched chain of amino acids.

 A compound containing two amino acids is specifically called a dipeptide;
 Three amino acids joined together in a chain constitute a tripeptide; and so on.
 Oligopeptide is loosely used to refer to peptides with 10 to 20 amino acid residues,
 A polypeptide is a long unbranched chain of amino acids.
 The bonds that link amino acids together in a peptide chain are called PEPTIDE BONDS. (BY
AMIDE BONDS)
 Peptide bond is a covalent bond between the carboxyl group of one amino acid and the amino
group of another amino acid.
 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 end with the free H3N + group is called the N-terminal end, and the end with the free COO−
group is called the C-terminal end.
ISOMERIC PEPTIDES

 Peptides that contain the same amino acids but in different order are different molecules
(constitutional isomers) with different properties.
 In the first dipeptide, the alanine is the N-terminal residue, and in the second molecule, it is the
C-terminal residue
 Five other arrangements of these three components are possible, each representing another
isomeric tripeptide: Ala–Cys–Ser, Ser–Ala–Cys, Ser–Cys–Ala, Cys–Ala–Ser, and Cys–Ser–Ala.
 For a pentapeptide containing five different amino acids, 120 isomers are possible.

BIOCHEMICALLY IMPORTANT SMALL PEPTIDES

 The two best-known peptide hormones, both produced by the pituitary gland, are OXYTOCIN
AND VASOPRESSIN.
 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 (Section
20-6).
o Structurally, these nonapeptides differ in the amino acid present in positions 3 and 8 of
the peptide chain.
o In both structures, an amine group replaces the C-terminal single-bonded oxygen atom.
 Oxytocin regulates uterine contractions and lactation.
 Vasopressin regulates the excretion of water by the kidneys; it also affects blood pressure
o ANOTHER NAME FOR VASOPRESSIN IS ANTIDIURETIC HORMONE (ADH). This name
relates to vasopressin’s function in the kidneys, which is to decrease urine output in
order to decrease water elimination from the body. Such action is necessary when the
body becomes dehydrated. 

SMALL PEPTIDE NEUROTRANSMITTERS

 ENKEPHALINS 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 and Leu-enkephalin, whose structures
differ only in the amino acid residue present at the C-terminal end of the peptide; this amino
acid difference is incorporated into their names.
 Met-enkephalin: Tyr–Gly–Gly–Phe–Met
 Leu-enkephalin: Tyr–Gly–Gly–Phe–Leu
 The pain-reducing effects of enkephalin action play a role in the “high” reported by long-
distance runners, in the competitive athlete’s managing to finish the game despite being
injured, and in the pain-relieving effects of acupuncture.
 The action of the prescription painkillers morphine and codeine is based on their binding at the
same receptor sites in the brain as the naturally occurring enkephalins.
 enkephalin pain relief is short-term, whereas morphine-codeine pain relief lasts much longer.
 Enzymes present in the brain readily hydrolyze the peptide linkages in enkephalins; morphine
and codeine do not have such linkages and are unaffected by the hydrolysis enzymes.
SMALL PEPTIDE ANTIOXIDANTS

 The tripeptide GLUTATHIONE (Glu–Cys–Gly) is present in significant concentrations in most cells

and is of considerable physiological importance as a regulator of oxidation –reduction
reactions.
 Specifically, glutathione functions as an antioxidant protecting cellular contents from oxidizing
agents such as peroxides and superoxides (highly reactive forms of oxygen often generated
within the cell in response to bacterial invasion)
 The amino acid Glu, an acidic amino acid, is bonded to Cys through the side-chain carboxyl
group rather than through its a-carbon carboxyl group.

GENERAL STRUCTURAL CHARACTERISTICS OF PROTEINS

 A protein is a peptide in which at least 40 amino acid residues are present.

 A monomeric protein is a protein in which only one peptide chain is present.
 Large proteins, those with many amino acid residues, usually are multimeric.
 A multimeric protein is a protein in which more than one peptide chain is present. The peptide
chains present in multimeric proteins are called protein subunits.
o The protein subunits within a multimeric protein may all be identical to each other or
different kinds of subunits may be present.
 Proteins, on the basis of chemical composition, are classified as simple or complex.
o A simple protein is a protein in which only amino acid residues are present. More than
one protein subunit may be present in a simple protein, but all subunits contain only
amino acids.
o A conjugated protein is a protein that has one or more nonamino-acid entities present
in its structure in addition to one or more peptide chains.
o A prosthetic group is a non-aminoacid group present in a conjugated protein.
o The non-amino-acid components present in a conjugated protein, which may be organic
or inorganic, are called prosthetic groups.
o Conjugated proteins may be further classified according to the nature of the prosthetic
group(s) present:
 Lipoproteins contain lipid prosthetic groups, glycoproteins contain
carbohydrate groups, (FIBRIN)
 metalloproteins contain specific metal ions, and so on
PRIMARY STRUCTURE OF PROTEINS
 Primary protein structure is the order in which amino acids are linked together in a protein.
 Primary protein structure always involves more than just the numbers and kinds of amino acids
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, was the first protein for which primary
structure was determined; the “sequencing” of its 51 amino acids was completed in 1953
 globin, a protein involved in oxygen storage in muscles; it contains 153 amino acids assembled
in the particular.
 The primary structure of a specific protein is always the same regardless of where the protein is
found within an organism.

SECONDARY STRUCTURE OF PROTEINS

 Secondary protein structure is the arrangement in space adopted by the backbone portion of a
protein.
 The two most common types of secondary structure are the alpha helix (a helix) and the beta
pleated sheet (b pleated sheet).
 The type of interaction responsible for both of these types of secondary structure is hydrogen
bonding between a carbonyl oxygen atom of a peptide linkage and the hydrogen atom of an
amino group of another peptide linkage farther along the protein backbone.
 EX ALPHA HELIX

An ALPHA HELIX STRUCTURE is a protein secondary structure in which a single protein chain adopts a
shape that resembles a coiled spring (helix), with the coil configuration maintained by hydrogen
bonds.

 Further details about alpha helix secondary protein structure are:

 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 (Figure 20-6b).
 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 (Figure 20-6b). This is
because one turn of the spiral includes 3.6 amino acid residues.
 4. All of the amino acid R groups extend outward from the spiral (Figure 20-6d). There is not
enough room for the R groups within the spiral.

THE BETA PLEATED SHEET

 A beta pleated sheet structure 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.
 Hydrogen bonds form between oxygen and hydrogen peptide linkage atoms that are either in
different parts of a single chain that folds back on itself (intrachain bonds) or between atoms in
different peptide chains in those proteins that contain more than one chain (interchain bonds). 
 In molecules where the b pleated sheet involves a single molecule, several U-turns in the protein
chain arrangement are needed in order to form the structure.
 This “U-turn structure” is the most frequently encountered type of b pleated sheet structure.

Further features of the b pleated sheet secondary protein structure are:

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

UNSTRUCTURED SEGMENTS

 Very few proteins have entirely a helix or b pleated sheet structures. Instead, only certain
portions of the molecules of most proteins are in these conformations.
 It is also possible to have both a helix and b pleated sheet structures within the same protein
 Helical structure and pleated sheet structure are found only in the portions of a protein where
the amino acid R groups present are relatively small; large R groups tend to disrupt both of
these types of secondary structure.
 The portions of a protein that have neither a helix nor b pleated sheet structure are called
unstructured segments.
o This designation is somewhat of a misnomer because all molecules of a given protein
exhibit identical unstructured segments.
 An unstructured protein segment is a protein secondary structure that is neither an a helix nor
a b pleated sheet.
TERTIARY STRUCTURE OF PROTEINS

 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

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. A variety of polar side chains
can be involved, especially those that possess the following functional groups

 Hydrogen bonds 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. In
aqueous solution, many proteins have their polar R groups pointing outward, toward the aqueous
solvent (which is also polar), and their nonpolar R groups pointing inward (away from the polar water
molecules).

QUARTERNARY STRUCTURE OF PROTEINS

 Quaternary structure is the highest level of protein organization. It is found only in multimeric
proteins
 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 (Figure 20-15). It is a tetramer in which there are two identical a subunits and two
identical b subunits. each subunit enfolds a heme group, the site where oxygen binds to the
protein.

ADDITIONAL NOTES:

CLASSIFICATION

Proteins are divided into three categories-simple, conjugated, and derived. On hydrolysis, simple
proteins yield only amino acids or derivatives of amino acids. On hydrolysis, conjugated proteins yield
amino acids plus some other type of com pound Conjugated protein consists of a simple protein
combined with a non-protein compound. Derived proteins are produced by the action of chemical,
enzymatic, and physical forces on the other two classes of protein. Derived proteins include proteoses,
peptones, polypeptides, tripeptides, and dipeptides. They also can be hydrolyzed to amino acids
Proteins are classified according to their solubility, composition, function, or shape.
CLASSIFICATION ACCORDING TO SOLUBILITY

Simple proteins are classified according to their solubility in various solvents and also as to
whether they are coagulated by heat.

CLASSIFICATION ACCORDING TO COMPOSITION

Conjugated proteins are classified according to the nature of the non-protein portion of the
molecule.

PROPERTIES OF SIMPLE PROTEINS

Type or protein solubility Coagulated by heat examples

Albumins Soluble in water and yes Egg albumin: serum
salt solutions albumin, lactalbumin

Globulins Yes Serum globulin,

Slightly soluble in lactoglobulin,
water, soluble in salt vegetable globulin
solutions

Albuminoids Insoluble in all neutral No Keratin in hair, nails,

solvents and in dilute feathers, collagen
acid and alkali

Histones Soluble in salt No Nucleohistone in

solutions, insoluble in thymus gland, globin in
very dilute NH4OH hemoglobin
CONJUGATED PROTEINS

Type Prosthetic Group (Non-protein examples

Portion of the Combination)

Nucleoproteins Nucleic acid chromosomes

Carbohydrate Mucin in saliva

Glycoprotein

Phosphoproteins Phosphate Casein in milk

Chromoproteins Chromophore group (color- Hemoglobin, hemocyanin,
producing group) flavoproteins, cytochrome

Lipoproteins Lipids Fibrin in blood

Metalloproteins Metals Ceruloplasmin (containing Cu)

and siderophilin (containing Fe)
in blood plasma