Download Chemistry 110 Enzymes

Chemistry 110
Bettelheim, Brown, Campbell & Farrell
Ninth Edition
Introduction to General,
Organic and Biochemistry
Chapter 23
Enzymes
Proteins that catalyze specific reactions.
Enzymes
¾All enzymes are proteins, with the exception of some
RNAs that catalyze their own splicing.
¾Enzymes cause remarkable rate enhancements, the rate of
a reaction can increase by a factor of up to 1020 over an
uncatalyzed reaction, but they cannot make a reaction go
that otherwise would not go.
¾Some enzymes catalyze the reaction of only one
compound, others are stereospecific, for example, enzymes
that catalyze the reactions of only L-amino acids or other
specific types of compounds, others only one type of bond,
for example, trypsin that catalyzes hydrolysis of peptide
bonds formed by the carboxyl groups of lysine and
arginine.
¾Most enzymes are specific for substrates.
Enzymes are Grouped by Their Function
Enzymes are classified into six major groups.
¾oxidoreductases:
oxidoreductases: catalyze oxidation-reduction reactions.
¾transferases:
transferases: catalyze group transfer reactions
¾hydrolases
ydrolases:: catalyze hydrolysis reactions.
¾lyases:
lyases: catalyze addition of groups to a double bond, or
removal of groups to create a double bond.
¾isomerases:
isomerases: catalyze isomerization reactions.
¾ligases:
ligases: catalyze the joining to two molecules.
¾Specific enzymes are commonly named after the reaction or
reactions they catalyze, for example: lactate dehydrogenase,
acid phosphatase.
¾Enzyme names always end in –ase .
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Terminology in Enzyme Chemistry
¾The apoenzyme is the protein part of an enzyme.
¾The cofactor is the nonprotein portion of an enzyme that
is involved in a chemical reaction; examples are metallic
ions such as Zn2+ and Mg2+.
¾A coenzyme is an organic cofactor for example heme.
Sometimes enzymes require both kinds of cofactors.
¾A substrate is the compound or compounds whose
reaction an enzyme catalyzes.
¾The active site is that specific portion of the enzyme to
which a substrate binds during reaction.
¾Enzymes cause chemical equilibria to be established
very rapidly, but the equilibrium composition is not
changed.
Enzyme Chemistry Terminology
¾Enzyme activation: any process that initiates or increases the
activity of an enzyme.
¾Enzyme inhibition: any process that makes an enzyme less
active or inactive.
¾Competitive inhibitor: any substance that binds to the active
site of an enzyme thus preventing binding of substrate.
¾Noncompetitive inhibitor: any substance that binds to a
portion of the enzyme other than the active site and thus
inhibits the activity of the enzyme.
¾Enzyme Activity is a measure of how much a reaction rate is
increased by the presence of the enzyme.
¾The rate of an enzyme-catalyzed reaction is affected by:
9enzyme concentration
9substrate concentration
9temperature
9pH
Mechanism of Enzyme Action
Enzyme + Substrate
Enzyme-Substrate
Complex
Enzyme-Product
Complex
Enzyme-Substrate
Activated Complex
Enzyme + Product
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The Mechanism of Enzyme Action
¾Both the lock-and-key model and the induced-fit model
emphasize the shape of the active site.
¾However it is the chemistry of the active site that is its most
important aspect.
¾In more than 65% of the enzymes studies done to date, just
five amino acids participate in the active sites.
¾These five amino acids are Histidine > Cystiene > Aspartic
Acid > Arginine > Glutamic Acid.
¾Four of these amino acids have either acidic or basic side
chains; the fifth has a sulfhydryl group (-SH).
Enzyme Regulation & Feedback
¾Feedback control is an enzyme-regulation process where the
product of a series of enzyme-catalyzed reactions inhibits an
earlier reaction in a sequence. The inhibition may be
competitive or noncompetitive.
¾A proenzyme or zymogen is 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
which 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 not only the primary
structure but also the tertiary structure, allowing the molecule
to achieve its active form.
¾Protein modification is similar. Here an enzyme has a group
added or removed, usually a phosphoryl residue, to activate it.
General Effects of Enzyme Inhibition
¾Antibiotics inhibit enzymes by affecting bacterial
metabolism.
¾Nerve Gases cause irreversible enzyme inhibition
– choline esterase inhibitors.
¾Insecticides – Most are reversible choline esterase
inhibitors.
¾Many heavy metal poisons work by irreversibly
inhibiting enzymes, especially cysteine residues.
¾Enzymes are commonly released from cells by
injury or disease – detecting them confirm the
injury or disease state.
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Enzyme Assays in Medicine
Enzyme Assays are useful in the diagnosis of various diseases.
Enzyme
Body Fluid
Disease Diagnosed
Alanine aminotransferase (ALT)
Serum
Hepatitis
Acid phosphatase
Alkaline phosphatase (ALP)
Amylase
Serum
Serum
Serum
Prostate cancer
Liver or bone disease
Pancreatic disease
Aspartate aminotransferase (AST) Serum,
Cerebrospinal
fluid
Lactate dehydrogenase (LDH)
Serum
Creatine phosphokinase (CK)
Serum
Phosphohexose isomerase (PHI)
Serum
Heart attack or
hepatitis
Heart attack
Heart attack
Heart attack
Enzymes in Medicine
¾Enzymes can be used to assay blood for specific
substances.
¾Immobilized enzymes provide simple tests for many
diseases or conditions.
¾Enzyme activators may be used medically to
activate zymogens or proenzymes – tissue
plasminogen activator therapy causes conversion of
plasminogen to plasmin to dissolve blood clots in
heart attack and strokes.
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