Chemistry 121(01) Winter 2010-11
Introduction to Organic Chemistry and Biochemistry
Instructor Dr. Upali Siriwardane (Ph.D. Ohio State)
E-mail: upali@chem.latech.edu
Office: 311 Carson Taylor Hall ; Phone: 318-257-4941;
Office Hours: MWF 8:00 am - 10:00 am;
TT 9:00 – 10:00 am & 1:00-2:00 pm.
December 17, 2010 Test 1 (Chapters 12-13)
January 19, 2011 Test 2 (Chapters 14,15 & 16)
February 7, 2011 Test 3(Chapters 17, 18 & 19)
February 23, 2011 Test 4 (Chapters 20, 21 & 22)
February 24, 2011
Comprehensive Make Up Exam:
Chemistry 121 Winter 2011 LA Tech
Chp. 21-1
Chapter 21. Enzymes and Vitamins
Sections
Chemistry 121 Winter 2011 LA Tech
Chp. 21-2
Chapter 21. Enzymes and Vitamins
21.1 General Characteristics of Enzymes
21.2 Nomenclature and Classification of Enzymes
21.3 Enzyme Structure
21.4 Models of Enzyme Action
21.5 Enzyme Specificity
21.6 Factors That Affect Enzyme Activity
21.7 Enzyme Inhibition
21.8 Regulation of Enzyme Activity: Allosteric Enzymes
21.9 Regulation of Enzyme Activity: Zymogens
21.10 Antibiotics That Inhibit Enzyme Activity
21.11 Medical Uses of Enzymes
21.12 Vitamins
21.13 Water-Soluble Vitamins
21.14 Fat-Soluble Vitamins
Chemistry 121 Winter 2011 LA Tech
Chp. 21-3
Chapter 21. Enzymes
Nomenclature and Classification
Activation Energy
Enzyme-Substrate Interaction
Cofactors and Coenzymes
Effect of pH and Temperature
Regulation of Enzyme Activity
Chemistry 121 Winter 2011 LA Tech
Chp. 21-4
Biological Catalysts
Typically very large proteins
Permit reactions to to “go” to conditions that the body
can tolerate
Can process millions of molecules per second
Are very specific-react with one or only a few types of
molecules (substrates).
Chemistry 121 Winter 2011 LA Tech
Chp. 21-5
Enzyme Nomenclature
Naming is easy compared to other organic compounds
Name is based on:
-What it reacts with
-how it reacts
-add -ase- ending
Examples
lactase
enzyme that reacts with lactose
pyruvate decarboxylase
remove carboxyl group from pyruvate
Chemistry 121 Winter 2011 LA Tech
Chp. 21-6
Classification of Enzymes
•
•
•
•
•
•
Oxidoreductases: catalyze oxidation-reduction.
Transferases: transfer of functional groups.
Hydrolases: catalyze hydrolysis reactions.
Lyases: catalyse the removal of chemical groups.
Isomerases: catalyze isomerization reactions.
Ligases: catalyze formation of chemical bonds, join two
molecules
Chemistry 121 Winter 2011 LA Tech
Chp. 21-7
Effect of Enzyme on Activation Energy
• Enzyme change how
a reaction will proceed.
• This reduces the
activation energy
• It makes it easier
Chemistry 121 Winter 2011 LA Tech
Chp. 21-8
Effect of Enzyme on Activation Energy
Chemistry 121 Winter 2011 LA Tech
Chp. 21-9
Effect of Substrate Concentration
• For non-catalyzed reactions
Reaction rate increase with concentration
• Enzyme catalyzed reactions
Also increase but only to a certain point
Vmax Maximum velocity
At Vmax, the enzyme is working as fast as it can
Chemistry 121 Winter 2011 LA Tech
Chp. 21-10
Effect of Substrate Concentration
Chemistry 121 Winter 2011 LA Tech
Chp. 21-11
Characteristics of Enzyme Active Sites
• Catalytic site
Where the reaction actually occurs.
• Binding site
Area that holds substrate in proper place.
Enzyme uses weak, non-covalent interactions to hold
the substrate in place based on alkyl (R) groups of
amino acids.
Shape is complementary to the substrate and determines
the specificity of the enzyme.
Sites are pockets or clefts on enzyme surface.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-12
Steps in Enzymatic Reactions
• Enzyme and substrate combine to form a complex
• Complex goes through a transition state
-which is not quite substrate or product
• A complex of the enzyme and the product is produced
• Finally the enzyme and product separate
All these steps are equilibria
Lets review each step
Chemistry 121 Winter 2011 LA Tech
Chp. 21-13
The Players
Chemistry 121 Winter 2011 LA Tech
Chp. 21-14
Formation of Enzyme-substrate Complex
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Chp. 21-15
Formation of the Transition State
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Chp. 21-16
Formation of the Enzyme-Product Complex
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Chp. 21-17
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Chp. 21-18
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Chp. 21-19
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Chp. 21-20
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Chp. 21-21
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Chp. 21-22
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Chp. 21-23
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Chp. 21-24
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Chp. 21-25
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Chp. 21-26
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Chp. 21-27
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Chp. 21-28
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Chp. 21-29
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Chp. 21-30
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Chp. 21-31
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Chp. 21-32
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Chp. 21-33
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Chp. 21-34
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Chp. 21-35
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Chp. 21-36
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Chp. 21-37
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Chp. 21-38
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Chp. 21-39
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Chp. 21-40
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Chp. 21-41
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Chp. 21-42
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Chp. 21-43
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Chp. 21-44
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Chp. 21-45
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Chp. 21-46
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Chp. 21-47
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Chp. 21-48
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Chp. 21-49
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Chp. 21-50
Chapter
Twenty One
Chemistry 121 Winter 2011 LA Tech
Enzymes
and Vitamins
Chp. 21-51
Enzymes and Vitamins cont’d
← CO 21.1
© Mark E. Gibson / CORBIS
Chemistry 121 Winter 2011 LA Tech
Chp. 21-52
Enzymes and Vitamins
← Fig. 21.1
Bread dough rises as
a result of the action
of yeast enzymes.
Steven Needham / Envision
Chemistry 121 Winter 2011 LA Tech
Chp. 21-53
Enzymes and Vitamins cont’d
Table 21.1
Chemistry 121 Winter 2011 LA Tech
Chp. 21-54
Enzymes and Vitamins cont’d
→ Fig. 21.2
The active site of an
enzyme is usually a
crevice-like region
formed as a result of
the protein’s
secondary and
tertiary structural
characteristics.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-55
Enzymes and Vitamins cont’d
Fig. 21.3
The lock-and-key model for enzyme activity.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-56
Enzymes and Vitamins cont’d
Fig. 21.4
The induced-fit model for enzyme
activity.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-57
Enzymes and Vitamins
cont’d
← Fig. 21.5
A schematic
diagram
representing
amino acid R
group interactions
that bind a
substrate to an
enzyme active
site.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-58
Enzymes and Vitamins cont’d
→ Fig. 21.6
A graph showing
the effect of
temperature on
the rate of
enzymatic
reaction.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-59
Enzymes and Vitamins cont’d
→ CC 21.1
Meckles / Ottawa / Photo Researchers
Chemistry 121 Winter 2011 LA Tech
Chp. 21-60
Enzymes and Vitamins cont’d
← Fig. 21.7
A graph showing the
effect of pH on the
rate of enzymatic
reaction.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-61
Enzymes and Vitamins cont’d
→ CC 21.2
© Leonard Lessin / Peter Arnold, Inc.
Chemistry 121 Winter 2011 LA Tech
© Leonard Lessin / Peter Arnold, Inc.
Chp. 21-62
Enzymes and Vitamins cont’d
→ Table 21.2
Chemistry 121 Winter 2011 LA Tech
Chp. 21-63
Enzymes and Vitamins cont’d
→ Fig. 21.8
A graph showing the
change in enzyme
activity with a change
in substrate
concentration.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-64
Enzymes and Vitamins cont’d
← Fig. 21.9
A graph showing the
change in reaction
rate with a change in
enzyme
concentration for an
enzymatic reaction.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-65
Enzymes and Vitamins cont’d
 CAG 21.1
Chemistry 121 Winter 2011 LA Tech
Chp. 21-66
Enzymes and Vitamins cont’d
→ Fig. 21.10
A comparison of an
enzyme with a
substance at its
active site (a) and an
enzyme with a
competitive inhibitor
at its active site (b).
Chemistry 121 Winter 2011 LA Tech
Chp. 21-67
Enzymes and Vitamins cont’d
← Fig. 21.11
The difference
between a
reversible
competitive
inhibitor and a
reversible
noncompetitive
inhibitor.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-68
Enzymes and Vitamins cont’d
→ Fig. 21.12
Conversion of
zymogen to a
proteolytic enzyme.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-69
Enzymes and Vitamins cont’d
CAG 21.2
Chemistry 121 Winter 2011 LA Tech
Chp. 21-70
Enzymes and Vitamins cont’d
← Fig. 21.13
Structures of selected
sulfa drugs in use
today as antibiotics.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-71
Enzymes and Vitamins cont’d
→ Fig. 21.14
Structures of selected
penicillins in use
today as antibiotics
Chemistry 121 Winter 2011 LA Tech
Chp. 21-72
Enzymes and Vitamins cont’d
Fig. 21.15
Selective binding of penicillin to the active site
of transpeptidase.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-73
Enzymes and Vitamins cont’d
→ Table 21.3
Chemistry 121 Winter 2011 LA Tech
Chp. 21-74
Enzymes and Vitamins cont’d
→ CC 21.3
Chemistry 121 Winter 2011 LA Tech
Chp. 21-75
Enzymes and Vitamins cont’d
→ Table 21.4
Chemistry 121 Winter 2011 LA Tech
Chp. 21-76
Enzymes and Vitamins cont’d
→ Fig. 21.16
Drawing of a blood
sample.
Saturn Stills / SPL / Photo Researchers
Chemistry 121 Winter 2011 LA Tech
Chp. 21-77
Enzymes and Vitamins cont’d
← Fig. 21.17
Rows of cabbage
plants.
© Jeff Greenberg / Peter Arnold, Inc.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-78
Enzymes and Vitamins cont’d
→ Fig. 21.18
The quantity of
vitamin D synthesized
by exposure of the
skin to sunlight
varies with latitude,
exposure time, and
skin pigmentation.
Melissa Grimes-Guy / Photo
Researchers
Chemistry 121 Winter 2011 LA Tech
Chp. 21-79
Enzymes and Vitamins cont’d
→ Table 21.5
Chemistry 121 Winter 2011 LA Tech
Chp. 21-80
Enzymes and Vitamins cont’d
→ Table 21.6
Chemistry 121 Winter 2011 LA Tech
Chp. 21-81
Enzymes and Vitamins cont’d
→ Table 21.7
Chemistry 121 Winter 2011 LA Tech
Chp. 21-82
•
•
•
•
•
•
•
•
Enzymes are catalysts and are not consumed in the reactions
Enzymes are proteins that act as a catalyst for biochemical
reactions
The human body has 1000s of enzymes
Enzymes are the most effective catalysts known
Most enzymes are globular proteins
A few enzymes are now known to be ribonucleic acids (RNA)
Enzymes undergo all the reactions of proteins including
denaturation
Enzyme activity is dramatically affected by:
• Alterations in pH
• Temperature
• Other protein denaturants
Chemistry 121 Winter 2011 LA Tech
Chp. 21-83
Simple and Conjugated Enzymes
• Enzymes are of two types: simple enzymes
and conjugated enzymes
• Simple enzyme: composed only of protein
(amino acid chains)
• Conjugated enzyme: Has a nonprotein part in
addition to a protein part.
• Apoenzyme: Protein part of a conjugated enzyme.
• A cofactor : Nonprotein part of a conjugated enzyme.
• A holoenzyme is the biochemically active conjugated
enzyme
• Apoenzyme + cofactor = holoenzyme (conjugated enzyme)
Chemistry 121 Winter 2011 LA Tech
Chp. 21-84
Cofactors
• Cofactors are important for the chemically
reactive enzymes
• Cofactors are small organic molecules or
Inorganic ions
• Organic molecule cofactors: also called as co-enzymes or
co-substrates
• Co-enzymes/co-substrates are derived from dietary
vitamins
• Inorganic ion cofactors
• Typical metal ion cofactors - Zn2+, Mg2+, Mn2+, and Fe2+
• Nonmetallic ion cofactor - Cl• Inorganic ion cofactors derived from dietary minerals
Chemistry 121 Winter 2011 LA Tech
Chp. 21-85
• Nomenclature: Most commonly named with
reference to their function
• Type of reaction catalyzed
• Identity of the substrate
• A substrate is the reactant in an enzyme-
catalyzed reaction:
• The substrate is the substance upon which the
enzyme “acts.”
• E. g., In the fermentation process sugar to be
converted to CO2, therefore in this reaction sugar
is the substrate
Chemistry 121 Winter 2011 LA Tech
Chp. 21-86
Three Important Aspects of the
Naming Process
1. Suffix -ase identifies it as an enzyme
• E.g., urease, sucrase, and lipase are all enzyme
designations
• Exception: The suffix -in is still found in the names of some
digestive enzymes, E.g., trypsin, chymotrypsin, and pepsin
2. Type of reaction catalyzed by an enzyme is
often used as a prefix
• E.g., Oxidase - catalyzes an oxidation reaction,
• E.g., Hydrolase - catalyzes a hydrolysis reaction
3. Identity of substrate is often used in addition
to the type of reaction
• E.g. Glucose oxidase, pyruvate carboxylase, and succinate
Chp. 21-87
dehydrogenase
Chemistry 121 Winter 2011 LA Tech
Practice Exercise
• Predict the function of the following
enzymes.
a. Maltase
b. Lactate dehydrogenase
c. Fructose oxidase
d. Maleate isomerase
Answers:
a. Hydrolysis of maltose;
b. Removal of hydrogen from
lactate ion;
Chemistry 121 Winter 2011 LA Tech
c. Oxidation of fructose;
Chp. 21-88
Six Major Classes
•
Enzymes are grouped into six major classes based on the
types of reactions they catalyze
Class
Reaction Catalyzed
1. Oxidoreductases
Oxidation-reductions
2. Transferases
Functional group transfer reactions
3. Hydrolases
Hydrolysis reactions
4. Lyases
Reactions involving addition or removal of groups form
double bonds
5. Isomerase
Isomerisation reactions
6. Ligases
Reactions involving bond formation coupled with ATP
hydrolysis
Chemistry 121 Winter 2011 LA Tech
Chp. 21-89
Oxidoreductase
• An oxidoreductase enzyme catalyzes an
oxidation–reduction reaction:
• Oxidation and reduction reactions are always
linked to one another
• An oxidoreductase requires a coenzyme that is
either oxidized or reduced as the substrate in the
reaction.
• E.g., Lactate dehydrogenase is an oxidoreductase
and the reaction catalyzed is shown below
Chemistry 121 Winter 2011 LA Tech
Chp. 21-90
Transferase
• A transferase is an enzyme that catalyzes the
transfer of a functional group from one
molecule to another
• Two major subtypes:
• Transaminases - catalyze transfer of an amino
group to a substrate
• Kinases - catalyze transfer of a phosphate group
from adenosine triphosphate (ATP) to a substrate
Chemistry 121 Winter 2011 LA Tech
Chp. 21-91
Hydrolase
• A hydrolase is an enzyme that catalyzes a
hydrolysis reaction
• The reaction involves addition of a water
molecule to a bond to cause bond breakage
• Hydrolysis reactions are central to the
process of digestion:
• Carbohydrases hydrolyze glycosidic bonds in
oligo- and polysaccharides (see reaction below)
• Proteases effect the breaking of peptide linkages
in proteins,
• 121
Lipases
effect
the breaking of ester linkages
in21-92
Chemistry
Winter 2011 LA
Tech
Chp.
Lyase
• A lyase is an enzyme that catalyzes the
addition of a group to a double bond or the
removal of a group to form a double bond in
a manner that does not involve hydrolysis or
oxidation
• Dehydratase: effects the removal of the
components of water from a double bond
• Hydratase: effects the addition of the
components of water to a double bonds
Chemistry 121 Winter 2011 LA Tech
Chp. 21-93
Isomerase, and Ligase
• An isomerase is an enzyme that catalyzes
the isomerization (rearrangement of atoms)
reactions.
• A ligase is an enzyme that catalyzes the
formation of a bond between two molecules
involving ATP hydrolysis:
• ATP hydrolysis is required because such
reactions are energetically unfavorable
• Require the simultaneous input of energy
obtained by a hydrolysis of ATP to ADP
Chemistry 121 Winter 2011 LA Tech
Chp. 21-94
Practice Exercise
Answers:
a.Transferase
b.Lyase
Chemistry 121 Winter 2011 LA Tech
Chp. 21-95
Enzyme Active Site
•
The active site:
Relatively small part
of an enzyme’s
structure that is
actually involved in
catalysis:
•
Place where substrate
binds to enzyme
• Formed due to folding
and bending of the
protein.
• Usually a “crevice
like” location in the
enzyme
• Some enzymes have
more than one active
site
Chemistry 121 Winter 2011 LA Tech
Chp. 21-96
Enzyme Substrate Complex
• Needed for the activity of enzyme
• Intermediate reaction species formed when
substrate binds with the active site
• Orientation and proximity is favorable and
reaction is fast
Chemistry 121 Winter 2011 LA Tech
Chp. 21-97
Two Models for Substrate Binding to
Enzyme
• Lock-and-Key model:
• Enzyme has a pre-determined shape for the
active site
• Only substrate of specific shape can bind with
active site
• Induced Fit Model:
• Substrate contact with enzyme will change the
shape of the active site
• Allows small change in space to accommodate
substrate (e.g., how a hand fits into a glove)
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Chp. 21-98
Forces That Determine Substrate
Binding
• H-bonding
• Hydrophobic interactions
• Electrostatic interactions
Chemistry 121 Winter 2011 LA Tech
Chp. 21-99
• Absolute Specificity:
• An enzyme will catalyze a particular reaction for only one
substrate
• This is most restrictive of all specificities (not common)
• E.g., Urease is an enzyme with absolute specificity
• Stereochemical Specificity:
• An enzyme can distinguish between stereoisomers.
• Chirality is inherent in an active site (amino acids are chiral
compounds)
• L-Amino-acid oxidase - catalyzes reactions of L-amino
acids but not of D-amino acids.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-100
• Group Specificity:
• Involves structurally similar compounds that have the same
functional groups.
• E.g., Carboxypeptidase: Cleaves amino acids one at a time
from the carboxyl end of the peptide chain
• Linkage Specificity:
• Involves a particular type of bond irrespective of the
structural features in the vicinity of the bond
• Considered most general of enzyme specificities
• E.g., Phosphatases: Hydrolyze phosphate–ester bonds in
all types of phosphate esters
Chemistry 121 Winter 2011 LA Tech
Chp. 21-101
Temperature
•
Higher temperature results in
higher kinetic energy which
causes an increase in number of
reactant collisions, therefore there
is higher activity.
• Optimum temperature:
Temperature at which the rate of
enzyme catalyzed reaction is
maximum
• Optimum temperature for human
enzymes is 37ºC (body
temperature)
• Increased temperature (high fever)
leads to decreased enzyme
activity
Chemistry
121 Winter 2011 LA Tech
Chp. 21-102
pH
•
•
•
•
•
•
•
pH changes affect enzyme
activity
Drastic changes in pH can
result in denaturation of
proteins
Optimum pH: pH at which
enzyme has maximum activity
Most enzymes have optimal
activity in the pH range of 7.0
- 7.5
Exception: Digestive enzymes
Pepsin: Optimum pH = 2.0
Trypsin: Optimum pH = 8.0
Chemistry 121 Winter 2011 LA Tech
Chp. 21-103
Substrate Concentration
•
Substrate Concentration: At a
constant enzyme concentration,
the enzyme activity increases
with increased substrate
concentration.
• Substrate saturation: the
concentration at which it
reaches its maximum rate and
all of the active sites are full
• Turnover Number: Number of
substrate molecules converted
to product per second per
enzyme molecule under
conditions of optimum
temperature and pH
Chemistry 121 Winter 2011 LA Tech
Chp. 21-104
Enzyme Concentration
• Enzyme
Concentration:
• Enzymes are not
consumed in the
reactions they
catalyze
• At a constant
substrate
concentration, enzyme
activity increases with
Chemistry
121 Winter 2011 in
LA Tech
increase
enzyme
Chp. 21-105
Practice Exercise
• Describe the effect that each of the following
changes would have on the rate of a reaction
that involves the substrate sucrose and the
intestinal enzyme sucrase.
a.
b.
c.
d.
Decreasing the sucrase concentration
Increasing the sucrose concentration
Lowering the temperature to 10ºC
Raising the pH from 6.0 to 8.0 when the optimum pH is 6.2
Answers:
a. Decrease
rate
Chemistry 121 Winter 2011 LA Tech
b. Increase
Chp. 21-106
• Enzyme Inhibitor: a substance that slows
down or stops the normal catalytic function
of an enzyme by binding to it.
• Competitive Inhibitors: Compete with the
substrate for the same active site
• Will have similar charge & shape
• Noncompetitive Inhibitors: Do not compete with
the substrate for the same active site
• Binds to the enzyme at a location other than
active site
Chemistry 121 Winter 2011 LA Tech
Chp. 21-107
Reversible Competitive Inhibition
• A competitive enzyme inhibitor: resembles
an enzyme substrate in shape and charge
• Binds reversibly to an enzyme active site and
the inhibitor remains unchanged (no reaction
occurs)
• The enzyme - inhibitor complex formation is
via weak interactions (hydrogen bonds, etc.).
• Competitive inhibition can be reduced by
simply increasing the concentration of the
substrate.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-108
Reversible Noncompetitive Inhibition
• A noncompetitive enzyme inhibitor
decreases enzyme activity by binding to a
site on an enzyme other than the active site.
• Causes a change in the structure of the
enzyme and prevents enzyme activity.
• Increasing the concentration of substrate
does not completely overcome inhibition.
• Examples: Heavy metal ions Pb2+, Ag+, and
Hg2+.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-109
Irreversible Inhibition
• An irreversible enzyme inhibitor inactivates
enzymes by forming a strong covalent bond
with the enzyme’s active site.
• The structure is not similar to enzyme’s normal
substrate
• The inhibitor bonds strongly and increasing
substrate concentration does not reverse the
inhibition process
• Enzyme is permanently inactivated.
• E.g., Chemical warfare agents (nerve gases) and
organophosphate insecticides
Chemistry 121 Winter 2011 LA Tech
Chp. 21-110
• Cellular processes continually produces
large amounts of an enzyme and plentiful
amounts of products if the processes are not
regulated.
• General mechanisms involved in regulation:
• Proteolytic enzymes and zymogenscovalent
modification of enzymes
• Feedback control Regulation of enzyme activity
by various substances produced within a cell
• The enzymes regulated are allosteric enzymes
Chemistry 121 Winter 2011 LA Tech
Chp. 21-111
Properties of Allosteric Enzymes
•
All allosteric enzymes have quarternary structure:
• Composed of two or more protein chains
• Have at least two of binding sites:
• Substrate and regulator binding site
• Active and regulatory binding sites are distinct from each
other:
• Located independent of each other
• Shapes of the sites (electronic geometry) are different
• Binding of molecules at the regulatory site causes changes in
the overall three dimensional structure of the enzyme:
• Change in three dimensional structure of the enzyme leads
to change in enzyme activity
• Some regulators increase enzyme activity – activators
Chemistry 121 Winter 2011 LA Tech
Chp. 21-112
• Some regulators decrease enzyme activity - inhibitors
Feedback Control
• Feedback Control: A process in which
activation or inhibition of the first reaction in
a reaction sequence is controlled by a
product of the reaction sequence.
• Regulators of a particular allosteric enzyme
may be:
• Products of entirely different pathways of
reaction within the cell
• compounds produced outside the cell
(hormones)
Chemistry 121 Winter 2011 LA Tech
Chp. 21-113
Proteolytic Enzymes and Zymogens
• 2nd mechanism of regulating enzyme
activity:
• Production of enzymes in an inactive forms (zymogens)
• Zymogens are “turned on” at the appropriate time and
place
• Example: proteolytic enzymes: Most digestive and bloodclotting enzymes are proteolytic enzymes
• Hydrolyze peptide bonds in proteins
• Proteolytic enzymes are generated in an inactive form and
then converted to their active form
Chemistry 121 Winter 2011 LA Tech
Chp. 21-114
Covalent Modification of Enzymes
•
3rd Mechanism for regulation of enzyme activity
• Covalent modification: A process in which enzyme activity is
altered by covalently modifying the structure of the enzyme:
• Involves adding or removing a group from an enzyme
• Most common covalent modification: addition and removal of
phosphate group:
• Phosphate group is often derived from an ATP molecule.
• Addition of the phosphate (phosphorylation) catalyzed by a
Kinase enzyme
• Removal of the phosphate group (dephosphorylation)
catalyzed by a phosphatase enzyme.
• Phosphate group is added to (or removed from) the R group
of a serine, tyrosine, or threonine amino acid residue in the
enzyme regulated.
Chemistry 121 Winter 2011 LA Tech
Chp. 21-115
• An anitibiotic is a substance that kills
bacteria or inhibits their growth
• Antibiotics usually inhibit specific enzymes
essential to life processes of bacteria
• Two families of antibiotics considered in this
discussion are sulfa drugs and penicillins
Chemistry 121 Winter 2011 LA Tech
Chp. 21-116
Sulfa Drugs
• Many derivatives of sulfanilamide collectively
called sulfa drugs exhibit antibiotic activities
• Sulfanilamide is structurally similar to PABA
(p-aminobenzoic acid)
• Many bacteria need PABA to produce
coenzyme, folic acid
• Sulfanilamide is a competitive inhibitor of
enzymes responsible for converting PABA to
folic acid in bacteria
• Folic acid deficiency retards bacterial growth
Chemistry 121 Winter 2011 LA Tech
Chp. 21-117
and that eventually kills them
Penicillins
• Accidently discovered by Alexander Fleming
in 1928
• Several naturally occurring penicillins and
numerous synthetic derivatives have been
produced
• All have structures containing a fourmembered Beta-lactam ring fused with a fivemembered thiazolidine ring
• Selectively inhibits transpeptidase by
covalent modification of serine residue
Chemistry 121 Winter 2011 LA Tech
Chp. 21-118
• Transpeptidase catalyzes the formation of
Cipro
• The antibiotic ciprofloxacin hydrochloride
(Cipro for short)
• Considered the best broad-spectrum
antibiotics because it is effective against
skin and bone infections as well as against
infections involving the urinary,
gastrointestinal, and respiratory systems
• It is the drug of choice for treatment of
traveler’s diarrhea
• Bacteria are slow to acquire resistance to
Chemistry 121 Winter 2011 LA Tech
Chp. 21-119
Cipro.
• Diagnose certain diseases:
• Enzymes produced in certain organ/tissues if
found in blood may indicate certain damage to
that organ/tissue
Chemistry 121 Winter 2011 LA Tech
Chp. 21-120
•
•
•
•
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Organic compounds
Must be obtained from dietary sources
Human body can’t synthesize in enough amounts
Essential for proper functioning of the body
Needed in micro and milligram quantities
1 Gram of vitamin B is sufficient for 500,000 people
Enough vitamin can be obtained from balanced diet
Supplemental vitamins may be needed after illness
Many enzymes contain vitamins as part of their structures conjugated enzymes
Two Classes
• Water Soluble and Fat Soluable
Synthetic and natural vitamins are same
• 13 Known vitamins
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Vitamin C
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Humans, monkeys, apes and guinea pigs need dietary vitamins
Co-substrate in the formation of structural protein collagen
Involved in metabolism of certain amino acids
100 mg/day saturates all body tissues - Excess vitamin is
excreted
RDA (mg/day):
• Great Britain: 30
• United States and Canada: 60
• Germany: 75
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Vitamin B
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The preferred and alternative names for the B vitamins
Thiamin (vitamin B1)
Riboflavin (vitamin B2)
Niacin (nicotinic acid, nicotinamide, vitamin B3)
Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine)
Folate (folic acid)
Vitamin B12 (cobalamin)
Pantothenic acid (vitamin B5)
Biotin
Exhibit structural diversity
Major function: B Vitamins are components of coenzymes
Chemistry 121 Winter 2011 LA Tech
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Vitamins A, D, E, K
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Involved in plasma membrane processes
More hydrocarbon like with fewer functional groups
Vitamin A
• Has role in vision - only 1/1000 of vitamin A is in retina
• 3 Forms of vitamin A are active in the body
• Derived from b-carotine
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Functions of Vitamin A
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Vision: In the eye- vitamin A combines with opsin protein to
form the visual pigment rhodopsin which further converts light
energy into nerve impulses that are sent to the brain.
Regulating Cell Differentiation - process in which immature
cells change to specialized cells with function.
• Examples: Differentiation of bone marrow cells white blood
cells and red blood cells.
Maintenance of the healthy of epithelial tissues via epithelial
tissue differentiation.
• Lack of vitamin A causes such surfaces to become drier
and harder than normal.
Reproduction and Growth: In men, vitamin A participates in
sperm development. In women, normal fetal development
during pregnancy requires vitamin A.
Chemistry 121 Winter 2011 LA Tech
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Vitamin D
• Two forms active in the body: Vitamin D2 and
D3
• Sunshine Vitamin: Synthesized by UV light
from sun
• It controls correct ratio of Ca and P for bone
mineralization (hardening)
• As a hormone it promotes Ca and P
absorption in intestine
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Vitamin E
• Four forms of Vitamin Es: a-, b-, g- and d-Vitamin
E
• Alpha-tocopherol is the most active biological
active form of Vitamin E
• Peanut oils, green and leafy vegetables and
whole grain products are the sources of vitamin
E
• Primary function: Antioxidant – protects against
oxidation of other compounds
Chemistry 121 Winter 2011 LA Tech
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Vitamin K
• Two major forms; K1 and K2
• K1 found in dark green, leafy vegetables
• K2 is synthesized by bacteria that grow in
colon
• Dietary need supply: ~1/2 synthesized by
bacteria and 1/2 obtained from diet
• Active in the formation of proteins involved
in regulating blood clotting
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