LOGO
Lecture 9
AMINO ACIDS, PROTEINS, AND ENZYMES
Organic Chemistry – FALL 2015
Course lecturer :
Jasmin Šutković
23 December 2015
CHAPTER OUTLINE
International University of Sarajevo
Book chapter 21
21.1 Introduction
21.2 Amino Acids
21.3 Acid–Base Behavior of Amino Acids
21.4 Peptides
21.5 FOCUS ON THE HUMAN BODY:
Biologically Active Peptides
21.6 Proteins
21.7 FOCUS ON THE HUMAN BODY:
Common Proteins
21.8 Protein Hydrolysis and Denaturation
21.9 Enzymes
21.10 FOCUS ON HEALTH & MEDICINE:
Using Enzymes to Diagnose and
Treat Diseases
Introduction
 Proteins are biomolecules that contain many
amide bonds, formed by joining amino acids
together.
Introduction
 The word protein comes from the Greek proteios meaning “of fi rst
importance.”
 Fibrous proteins, like keratin in hair, skin, and nails and collagen in
connective tissue, give support and structure to tissues and cells.
 Protein hormones and enzymes regulate the body’s metabolism/
 Transport proteins carry substances through the blood, and storage
proteins store elements and ions in organs.
 Contractile proteins control muscle movements, and
immunoglobulinsare proteins that defend the body against foreign
substances
AMINO ACIDS
 To understand protein properties and structure, we must
first learn about the amino acids that compose them.
 Amino acids contain two functional groups—an amino group
(NH2) and a carboxyl group (COOH). In most naturally occurring
amino acids, the amino group is bonded to the α carbon, the carbon
adjacent to the carbonyl group, making them 𝛂-amino acids.
• All amino acids have common names, which are abbreviated by a three-letter
or one-letter designation. For example, glycine is often written as the threeletter abbreviation Gly, or the one-letter abbreviation G. These abbreviations
are also given in Table 21.2.
• Amino acids never exist in nature as neutral molecules with all uncharged
atoms. Since amino acids contain a base (NH2 group) and an acid (COOH),
proton transfer from the acid to the base forms a salt called a zwitterion,
which contains both a positive and a negative charge.
• These saltshave high melting points and are water soluble.
• Humans can synthesize only 10 of the 20 amino acids needed for
proteins. The remaining 10, called essential amino acids, must be
obtained from the diet and consumed on a regular, almost daily basis.
• Diets that include animal products readily supply all of the needed amino
acids.
STEREOCHEMISTRY OF AMINO ACIDS
 Except for the simplest amino acid, glycine, all other amino acids
have a chirality center—a carbon bonded to four different
groups—on the 𝛂 carbon.
 Thus, an amino acid like alanine (R = CH3) has two possible
enantiomers, drawn below in both three-dimensional representations
with wedges and dashed bonds, and Fischer projections.
ACID–BASE BEHAVIOR OF AMINO ACIDS
As mentioned in Section 21.2, an amino acid contains both a
basic amino group (NH2) and an acidic carboxyl group (COOH).
As a result, proton transfer from the acid to the base forms a zwitterion,
a salt that contains both a positive and a negative charge.
The zwitterion is neutral; that is, the net charge on the salt is zero.
 Thus, alanine exists in one of three different forms
depending on the pH of the solution in which it is
dissolved. At the physiological pH of 7.4, neutral
amino acids are primarily in their zwitterionic forms.
 The pH at which the amino acid exists primarily in its
neutral form is called its isoelectric point,
abbreviated as pI.
 The isoelectric points of neutral amino acids are
generally around 6.
PEPTIDES
When amino acids are joined together by amide bonds,
they form larger molecules called peptides and proteins.
•A dipeptide has two amino acids joined together by
one amide bond.
•A tripeptide has three amino acids joined together by
two amide bonds
 Fischer projection formulas are also used for compounds
like aldohexoses that contain several chirality centers.
 The letters D and L are used to label all monosaccharides, even
those with many chirality centers.
 The configuration of the chirality center farthest from the
carbonyl group determines whether a monosaccharide is D or L
Polypeptides and proteins both have many amino acids joined
together in long linear chains, but the term protein is usually reserved
for polymers of more than 40 amino acids.
FOCUS ON THE HUMAN BODY
BIOLOGICALLY ACTIVE PEPTIDES
 NEUROPEPTIDES—ENKEPHALINS for PAIN RELIEF
 Enkephalins, pentapeptides synthesized in the brain, act as
pain killers and sedatives by binding to pain receptors.
 The addictive narcotic analgesics morphine and heroin
(Section 18.5) bind to the same receptors as the enkephalins,
and thus produce a similar physiologica response.
 Enkephalins are related to a group of larger polypeptides
called endorphins that contain 16–31 amino acids.
Endorphins also block pain and are thought to produce the
feeling of well-being experienced by an athlete after
excessive or strenuous exercise.
FOCUS ON THE HUMAN BODY
BIOLOGICALLY ACTIVE PEPTIDES
 PEPTIDE HORMONES—OXYTOCIN AND
VASOPRESSIN of calories per gram.
 Oxytocin and Vasopressin are cyclic nonapeptide hormones
secreted by the pituitary gland.
 Their sequences are identical except for two amino acids, yet this
is enough to give them very different biological activities.
Oxytocin and Vasopressin
 Oxytocin stimulates the contraction of uterine
muscles, and it initiates the flow of milk in nursing
mothers (Figure 21.2). Oxytocin, sold under the trade
names Pitocin and Syntocinon !
 Vasopressin, also called anti-diuretic hormone
(ADH), targets the kidneys and helps to keep the
electrolytes in body fluids in the normal range.
Vasopressin is secreted when the body is dehydrated
and causes the kidneys to retain fluid, thus decreasing
the volume of the urine
PROTEINS
 To understand proteins, the large polymers of
amino acids that are responsible for so much of
the structure and function of all living cells, we
must learn about four levels of structure, called
the primary, secondary, tertiary, and
quaternary structure of proteins.
PRIMARY STRUCTURE
The primary structure of a protein is the particular
sequence of amino acids that is joined together by
peptide bonds.
The most important element of this primary structure is
the amide bond that joins the amino acids.
SECONDARY STRUCTURE
 The three-dimensional arrangement of localized
regions of a protein is called its secondary structure.
 These regions arise due to hydrogen bonding
between the N-H proton of one amide and the C-O
oxygen of another.
 Two arrangements that are particularly stable are called
the 𝛂-helix and the 𝛃-pleated sheet.
𝛂-helix
 The 𝛂-helix forms when a peptide chain twists into a righthanded or clockwise spiral, as shown in figure.
α-helix
 Several important features characterize an α-helix :
β-Pleated Sheet
 The 𝛃-pleated sheet forms when two or more peptide
chains, called strands, line up side-byside, as shown
in Figure 21.5.
 All β-pleated sheets have the following characteristics:
 The C O and N H bonds lie in the plane of the sheet.
 Hydrogen bonding often occurs between the N H and C O
groups of nearby amino acid residues.
 The R groups are oriented above and below the plane of the
sheet, and alternate from one side to the other along a given
strand.
TERTIARY AND QUATERNARY
STRUCTURE
 The three-dimensional shape adopted by the entire
peptide chain is called its tertiary structure.
 A peptide generally folds into a shape that maximizes its
stability.
 In addition, polar functional groups hydrogen bond with
each other (not just water), and amino acids with charged
side chains like –COO– and –NH3 + can stabilize tertiary
structure by electrostatic interactions.
 Finally, disulfide bonds are the only covalent bonds
that stabilize tertiary structure
Celluloze
FOCUS ON THE HUMAN BODY
COMMON PROTEIN
 Proteins are generally classified according to
their three-dimensional shapes.
 Fibrous proteins are composed of long linear polypeptide chains that
are bundled together to form rods or sheets. These proteins are
insoluble in water and serve structural roles, giving strength and
protection to tissues and cells.
 Globular proteins are coiled into compact shapes with hydrophilic
outer surfaces that make them water soluble. Enzymes and transport
proteins are globular to make them soluble in blood and other aqueous
environments.
α-KERATINS
 𝛂-Keratins are the proteins found in hair, hooves,
nails, skin, and wool.
 They are composed almost exclusively of long sections
of α-helix units, having large numbers of alanine and
leucine residues.
 Since these nonpolar amino acids extend outward from
the α-helix, these proteins are very insoluble in water.
 Two α-keratin helices coil around each other, forming a
structure called a supercoil or superhelix
COLLAGEN
 Collagen, the most abundant protein in vertebrates, is found in
connective tissues such as bone, cartilage, tendons, teeth, and
blood vessels.

 Glycine and proline account for a large fraction of its amino acid
residues.
 Collagen forms an elongated left-handed helix, and then three of
these helices wind around each other to form a right-handed
superhelix or triple helix.
 Two views of the collagen superhelix are shown in Figure 21.13.
HEMOGLOBIN AND
MYOGLOBIN
 Hemoglobin and myoglobin, two globular proteins, are called
conjugated proteins because they are composed of a protein unit
and a nonprotein molecule.
 In hemoglobin and myoglobin, the nonprotein unit is called heme, a
complex organic compound containing the Fe2+ ion complexed
with a large nitrogen-containing ring system.
 The Fe2+ ion of hemoglobin and myoglobin binds oxygen.
 Hemoglobin, which is present in red blood cells, transports oxygen to
wherever it is needed in the body, whereas myoglobin stores oxygen
in tissues.
Sickle cell anemia
 Is a hereditary blood disorder,
characterized by red blood cells
that assume an abnormal, rigid,
sickle shape.
 Sickling decreases the cells'
flexibility and results in a risk of
various complications.
 The sickling occurs because of a
mutation in the haemoglobin gene.
Individuals with one copy of the
defunct gene display both normal
and abnormal haemoglobin!
PROTEIN HYDROLYSIS AND
DENATURATION
 The properties of a protein are greatly altered and often entirely
destroyed when any level of protein structure is disturbed.
PROTEIN HYDROLYSIS
 The hydrolysis of the amide bonds in a protein forms the
individual amino acids that comprise the primary structure.
PROTEIN DENATURATION
 Denaturation is the process of altering the shape of a protein
without breaking the amide bonds that form the primary
structure.
 High temperature, acid, base, and even agitation can disrupt the
non-covalent interactions that hold a protein in a specific shape.
 As a result, denaturation causes a globular protein to uncoil into an
undefined randomly looped structure.
ENZYMES
 We conclude the discussion of proteins with enzymes,
proteins that serve as biological catalysts for
reactions in all living organisms.
 Enzymes are crucial to the biological reactions that occur
in the body, which would otherwise often proceed too
slowly to be of any use. In humans, enzymes must
catalyze reactions under very specific physiological
conditions, usually a pH around 7.4 and a temperature of
37 °C.
CHARACTERISTICS OF ENZYMES
 Enzymes greatly enhance reaction rates. An
enzyme-catalyzed reaction can be 106 to 1012
times faster than a similar uncatalyzed
reaction.
 Enzymes are very specific.
 Example : carboxypeptidase A, digestive
enzyme that breaks down proteins, catalyzes the
hydrolysis of a specific type of peptide bond—the
amide bond closest to the C-terminal end of the
protein.
Coenzyme and cofactors
 A cofactor is a metal ion or a nonprotein
organic molecule needed for an
enzymecatalyzed reaction to occur.
 An organic compound that serves as an
enzyme cofactor is called a coenzyme
HOW ENZYMES WORK
 An enzyme contains a region called the
active site that binds the substrate,
forming an enzyme – substrate
complex.
 In biochemistry, a substrate is a molecule
upon which an enzyme acts !
E + S ⇌ ES → EP ⇌ E + P
Example – lock and key
model
 Two models have been proposed to explain the
specificity of a substrate for an enzyme’s active site: the
lock-and-key model and the induced-fit model.
 In the lock-and-key model, the shape of the active
site is rigid!
Other example – induced fit
model
 In the induced-fit model, the shape of
the active site is more flexible.
ENZYME INHIBITORS
 Some substances bind to enzymes and in
the process, greatly alter or destroy the
enzyme’s activity
 An inhibitor is a molecule that causes
an enzyme to lose activity.
 An inhibitor can bind to an enzyme
reversibly or irreversibly.
• A reversible inhibitor binds to an enzyme but
then enzyme activity is restored when the
inhibitor is released.
• An irreversible inhibitor covalently binds to an
enzyme, permanently destroying its activity.
ZYMOGENS
 Sometimes an enzyme is synthesized in an inactive form,
and then it is converted to its active form when it is
needed. The inactive precursor of an enzyme is called a
zymogen or proenzyme