Spencer L. Seager
Michael R. Slabaugh
www.cengage.com/chemistry/seager
Chapter 20:
Enzymes
Jennifer P. Harris
ENZYME CHARACTERISTICS
• Enzymes are proteins that catalyze chemical reactions. They
speed up chemical reactions by lowering activation energies.
ENZYME CHARACTERISTICS (continued)
• Enzymes are specific in the type of reactions they catalyze.
• Absolute specificity acts only on one substance.
• Relative specificity acts on structurally related
substances.
• Stereochemical specificity distinguishes between
stereoisomers.
ENZYME CHARACTERISTICS (continued)
• Enzyme activity can be regulated.
• The cell controls rates of reactions.
• The cell controls amount of any product formed by
regulating the action of enzymes.
CLASSIFYING AND NAMING ENZYMES
• The earliest enzymes have names with –in to indicate their
protein composition.
• Examples:
• pepsin
• trypsin
• chymotrypsin
CLASSIFYING AND NAMING ENZYMES
(continued)
• Many known enzymes created the need of a systematic
nomenclature system (Enzyme Commission (EC) system),
which:
• has six major classes based on type of reaction catalyzed.
• names the specific substrate and functional group acted
upon as well as the type of reaction catalyzed.
• ends the name in –ase.
• A substrate is the substance that undergoes a chemical
change catalyzed by an enzyme.
CLASSIFYING AND NAMING ENZYMES
(continued)
CLASSIFYING AND NAMING ENZYMES
(continued)
• Enzymes also have common names, which:
• are shorter than EC name.
• can be formed by one of the following methods:
• adding –ase to the name of the substrate.
• adding –ase to a combination of the substrate name
and type of reaction.
• include examples, such as the enzyme for:
• the substrate urea, which has a common name of
urease.
• the substrate alcohol and a dehydrogenation reaction
type, which has a common name of alcohol
dehydrogenase.
CLASSIFYING AND NAMING ENZYMES
(continued)
ENZYME COFACTORS
• Some enzymes require a second substance present
(cofactor) in order to be active, not a true prosthetic group
(only weakly bound to the enzyme).
• Cofactors can be a nonprotein molecule or ion.
• If the cofactor is an organic molecule, it is called a
coenzyme.
• An apoenzyme is the catalytically inactive protein formed by
the removal of the cofactor.
Apoenzyme + cofactor (coenzyme or inorganic ion) → active enzyme
• Coenzymes are often derived from vitamins.
ENZYME COFACTORS (continued)
ENZYME MECHANISM
• All enzymes have an active site – the location on the enzyme
where a substrate binds and catalysis occurs.
• Enzymes complex with the substrate and the chemical
reaction proceeds.
E
+
S
⇆ ES → E + P
enzyme substrate enzymeenzyme product
substrate
complex
ENZYME MECHANISM (continued)
• Specific example:
ENZYME MECHANISM (continued)
• There are two main theories on active sites:
• Lock-and-key theory states that the substrate has a
shape that exactly fits the active site. This explains
enzyme specificity.
ENZYME MECHANISM (continued)
• Induced-fit theory states that the conformation of the active
site changes to accommodate an incoming substrate.
ENZYME ACTIVITY
• Enzyme activity is the rate at which an enzyme catalyzes a
reaction.
• Turnover number is the number of substrate molecules
acted on by one enzyme molecule per minute.
• Enzyme international unit is the quantity of enzyme that
catalyzes the conversion of 1 µmol of substrate per minute.
• An enzyme assay is an experiment that measures enzyme
activity.
ENZYME ACTIVITY (continued)
FACTORS AFFECTING ACTIVITY
• The more enzyme present, the higher the enzyme
concentration and the faster substrate reacts.
FACTORS AFFECTING ACTIVITY (continued)
• Increasing substrate concentration increases the reaction rate
until enzymes become saturated (Vmax).
FACTORS AFFECTING ACTIVITY (continued)
• Enzymes have an optimum temperature range (usually 2540°C), above or below which they begin to denature.
FACTORS AFFECTING ACTIVITY (continued)
• Enzymes have optimum pH values (usually around 7), above
and below which the rate decreases.
FACTORS AFFECTING ACTIVITY (continued)
ENZYME INHIBITION
• Inhibitors decrease enzyme activity.
• Irreversible inhibitors covalently bond with the enzyme and
render it inactive.
• Many poisons are irreversible inhibitors.
Examples: CN-, Hg2+, and Pb2+
• Some antibiotics are irreversible inhibitors.
• Examples: Sulfa drugs and penicillins inhibit specific
enzymes essential to the life processes of bacteria.
• Penicillins interfere with transpeptidase, an enzyme
that is important in bacterial cell wall construction.
• Inability to form strong cell walls prevents the bacteria
from surviving.
ENZYME INHIBITION (continued)
ENZYME INHIBITION (continued)
• The cyanide ion:
• is an irreversible enzyme inhibitor.
• is extremely toxic.
• acts very rapidly.
• interferes with the operation of an iron-containing enzyme
(cytochrome oxidase) by forming a very stable complex.
• does not allow the enzyme to function properly.
• stops cellular respiration.
• causes death in minutes.
ENZYME INHIBITION (continued)
• The cyanide poisoning antidote:
• must be administered quickly.
• can be sodium thiosulfate (same substance known as
“hypo” in developing photographic film), which:
• converts the cyanide ion to a thiocyanate ion, which:
• does not bind to the iron of cytochrome oxidase.
ENZYME INHIBITION (continued)
• Heavy metal toxicity:
• is due to ability to render the protein part of enzymes
ineffective.
• occurs when metals combine with the –SH groups found
on many enzymes.
• causes nonspecific protein denaturation.
• Mercury and lead poisoning can cause permanent
neurological damage.
ENZYME INHIBITION (continued)
• Heavy-metal poisoning treated by administering chelating
agents (substances that combine with the metal ions and
hold them very tightly).
• An example of a chelating agent is
ethylenediaminetetraacetic acid, EDTA , which:
• chelates all heavy metals except mercury.
• The calcium salt of EDTA administered intravenously.
• Calcium ions are displaced by heavy-metal ions that bind to
the chelate more tightly.
• The heavy metal-EDTA complex is soluble in body fluids and
is excreted in the urine.
ENZYME INHIBITION (continued)
• Reversible
inhibitors reversibly
bind with enzymes.
• Competitive
reversible inhibitors
compete with
substrate for
binding at the active
site.
• Action can be
reversed by
increasing substrate
concentration
(LeChâtelier’s
principle).
ENZYME INHIBITION (continued)
• Sulfa drug on bacteria is an example of competitive enzyme
inhibition.
• Folic acid normally synthesized within the bacteria by
process that requires p-aminobenzoic acid.
• Sulfanilamide resembles p-aminobenzoic acid and competes
with it for the active site of the bacterial enzyme.
• Sulfanilamide can prevent bacterial growth.
ENZYME INHIBITION (continued)
• Noncompetitive reversible inhibitors bind to the enzyme at
a location other than the active site.
• Substrate concentration doesn’t affect inhibitor action.
ENZYME REGULATION (continued)
ENZYME REGULATION
• Zymogens or proenzymes are an inactive precursor of an
enzyme.
• Some enzymes are stored as inactive zymogens.
• They are released when needed and activated at the location
where the reaction occurs.
ENZYME REGULATION (continued)
ENZYME REGULATION (continued)
• Allosteric regulation of allosteric enzyme activity is altered
by the binding of a modulator.
• Modulators can increase allosteric enzyme activity
(activator) or decrease it (inhibitor).
• Feedback inhibition is an example of a modulator
decreasing the activity of an allosteric enzyme.
ENZYME REGULATION (continued)
• The synthesis of isoleucine is a five-step process.
• Threonine deaminase (enzyme for first step) is subject to
inhibition from isoleucine (final product).
• Isoleucine and threonine have very different structures;
therefore, this is an example of a noncompetitive
inhibitor.
• Isoleucine binds to an allosteric site, not an active
site.
ENZYME REGULATION (continued)
• Enzyme induction is the synthesis of an enzyme in
response to a cellular need.
• This is an example of genetic control.
• The synthesis of -galactosidase is an example of
enzyme induction.
MEDICAL APPLICATIONS
• Changes in blood serum concentrations of specific enzymes
can be used to detect cell damage or uncontrolled growth
(cancer).
• The measurement of enzyme concentrations in blood serum
has become a major diagnostic tool, particularly in diagnosing
diseases of the heart, liver, pancreas, prostate, and bones.
MEDICAL APPLICATIONS (continued)