Download Camp 1 - Dr. Paul J. McElligott

22
General, Organic, and
Biochemistry, 7e
Bettelheim,
Brown, and March
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22-1
22 Chapter 22
Enzymes
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22-2
22 Enzyme Catalysis
•
Enzyme: a biological catalyst
• with the exception of some RNAs that catalyze their own
splicing, all enzymes are proteins
• enzymes can increase the rate of a reaction by a factor of up
to 1020 over an uncatalyzed reaction
• some catalyze the reaction of only one compound
( NH2 )C=O + H2 O ureas e
Urea
2NH3 + CO2
• others are stereospecific; for example, enzymes that
catalyze the reactions of only L-amino acids
• others catalyze reactions of specific types of compounds or
bonds; for example, trypsin that catalyzes hydrolysis of
peptide
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Arg
22 Classification of Enzymes
• Enzymes are commonly named after the reaction
or reactions they catalyze
• example: lactate dehydrogenase, acid phosphatase
• Enzymes are classified into six major groups
• oxidoreductases: oxidation-reduction reactions
• transferases: group transfer reactions
• hydrolases: hydrolysis reactions
• lyases: addition of groups to a double bond, or removal
of groups to create a double bond
• isomerases: isomerization reactions
• ligases: the joining to two molecules
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22-4
22 Terms in Enzyme Chem
• apoenzyme: the protein part of an enzyme
• cofactor: a nonprotein portion of an enzyme that is
involved in a chemical reaction; examples are metallic
ions such as Zn2+ and Mg2+
• coenzyme: an organic cofactor; an example is heme
• substrate: the compound or compounds whose
reaction an enzyme catalyzes
• active site: the specific portion of the enzyme to which
a substrate binds during reaction
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22 Schematic of an Active Site
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22 Terms in Enzyme Chem
• activation: any process that initiates or increases the
activity of an enzyme
• inhibition: any process that makes an enzyme less
active or inactive
• competitive inhibitor: an substance that binds to the
active site of an enzyme thus preventing binding of
substrate
• noncompetitive inhibitor: any substance that binds to a
portion of the enzyme other than the active site and
thus inhibits the activity of the enzyme
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22 Enzyme Activity
• Enzyme activity: a measure of how much a
reaction rate is increased
• We examine how the rate of an enzyme-catalyzed
reaction is effected by
•
•
•
•
enzyme concentration
substrate concentration
temperature
pH
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22 Enzyme Activity
• Enzyme concentration
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22 Enzyme Activity
• Substrate concentration
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22 Enzyme Activity
• Temperature
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22 Enzyme Activity
• pH
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22 Mechanism of Action
• Lock-and-key model
• the enzyme is a rigid three-dimensional body
• the enzyme surface contains the active site
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22 Mechanism of Action
• Induced-fit model
• the active site becomes modified to accommodate the
substrate
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22 Mechanism of Action
• the induced-fit model explains competitive inhibition
• the inhibitor fits into the active site, preventing the
substrate from entering
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22 Mechanism of Action
• both the lock-and-key model and the induced-fit model
emphasize the shape of the active site
• however, the chemistry of the active site is the most
important
• just five amino acids participate in the active sites in
more than 65% of the enzymes studies to date
• these five are His > Cys > Asp > Arg > Glu
• four these amino acids have either acidic or basic side
chains; the fifth has a sulfhydryl group (-SH)
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22 Mechanism of Action
• the mechanism of noncompetitive inhibition
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22 Mechanism of Action
• we can distinguish between competitive and
noncompetitive inhibition by the enzyme kinetics in the
absence and presence of the inhibitor
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22 Enzyme Regulation
• Feedback control: an enzyme-regulation process
where the product of a series of enzymecatalyzed reactions inhibits an earlier reaction in
a sequence
feedb ack in hibition
A
E1
B
E2
C
E3
D
• the inhibition may be competitive or noncompetitive
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22 Enzyme Regulation
• Proenzyme (zymogen): an inactive form of an
enzyme that must have part of its polypeptide
chain cleaved before it becomes active
• an example is trypsin, a digestive enzyme
• it is synthesized and stored as trypsinogen, which has
no enzyme activity
• it becomes active only after a six-amino acid fragment
is hydrolyzed from the N-terminal end of its chain
• removal of this small fragment changes in not only the
primary structure but also the tertiary structure,
allowing the molecule to achieve its active form
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22 Enzyme Regulation
• Allosterism: a type of enzyme regulation based
on an event occurring on the enzyme at a place
other than the active site but that creates a
change in the active site
• an enzyme regulated by this mechanism is called an
allosteric enzyme
• allosteric enzymes often have multiple polypeptide
chains
• negative modulation: inhibition of an allosteric enzyme
• positive modulation: stimulation of an allosteric
enzyme
• regulator: a substance that binds to an allosteric
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enzyme
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22 The Allosteric Effect
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22 Enzyme Regulation
• Protein modification: the process of affecting
enzyme activity by covalently modifying it
• the best known examples of protein modification
involve phosphorylation/dephosphorylation
• example: pyruvate kinase (PK) is the active form of the
enzyme; it is inactivated by phosphorylation to
pyruvate kinase phosphate (PKP)
ATP
active
AD P
inactive
kinase
PK
PKP
phosph atase
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Pi
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22 Enzyme Regulation
• Isoenzyme: an enzyme that occurs in multiple
forms; each catalyzes the same reaction
• example: lactate dehydrogenase (LDH) catalyzes the
oxidation of lactate to pyruvate
• the enzyme is a tetramer of H and M chains
• H4 is present predominately in heart muscle
• M4 is present predominantly in the liver and in skeletal
muscle
• H3M, H2M2, and HM3 also exist
• H4 is allosterically inhibited by high levels of pyruvate
while M4 is not
• H4 in serum correlates with the severity of heart attack
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22 Enzymes in Medicine
• Enzyme assays useful in medical diagnosis
En zyme
Body Flu id
D iseas e Diagnosed
Alan ine amin otrans ferase (ALT)
Acid phosp hatase
Alk alin e phosp hatase (ALP)
Amylase
Serum
Hepatitis
Prostate cancer
Liver or bone dis ease
Pan creatic diseas e
Serum
Serum
Serum
As partate aminotransferase (AST) Serum,
Cereb rosp in al
fluid
Lactate dehydrogenas e (LD H)
Serum
Creatin e phosph ok inase (CK)
Serum
Ph os phohexose isomeras e (PHI)
Serum
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Heart attack or
hep atitis
Heart attack
Heart attack
Heart attack
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22 Enzymes
End
Chapter 22
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