enzymes
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BettleheimTRANSCRIPT
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Chapter 23: Enzymes
Chem 104 K. Dunlap
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EnzymesRibbon diagram of cytochrome c oxidase, the enzyme that directly uses oxygen during respiration.
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Enzyme CatalysisEnzyme: A biological catalyst.– With the exception of some RNAs that catalyze their own
self-cleavage, all enzymes are proteins.– Enzymes can increase the rate of a reaction by a factor of 109 to 1020 over
an uncatalyzed reaction.– Some catalyze the reaction of only one compound.
– Others are stereoselective; 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 catalyzes hydrolysis of peptide bonds formed by the carboxyl groups of Lys and Arg.
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Enzyme CatalysisTrypsin catalyzes the hydrolysis of peptide bonds formed by the carboxyl group of lysine and arginine.
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Classification of EnzymesEnzymes are commonly named after the reaction or reactions they catalyze.– Example: lactate dehydrogenase, acid phosphatase.
Enzymes are classified into six major groups according to the type of reaction catalyzed:– Oxidoreductases: Oxidation-reduction reactions.– Transferases: Group transfer reactions.– Hydrolases: Hydrolysis reactions.– Lyases: Addition of two groups to a double bond, or removal of
two groups to create a double bond.– Isomerases: Isomerization reactions.– Ligases: The joining to two molecules.
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Classification of Enzymes1. Oxidoreductase:
2. Transferase:
3. Hydrolase:
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Classification of Enzymes
4. Lyase:
5. Isomerase:
6. Ligase:
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Enzyme Terminology
Apoenzyme: The protein part of an enzyme.Cofactor: A nonprotein portion of an enzyme that is necessary for catalytic function; examples are metallic ions such as Zn2+ and Mg2+.Coenzyme: A nonprotein organic molecule, frequently a B vitamin, that acts as a cofactor.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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Schematic of an Active Site
Schematic diagram of the active site of an enzyme and the participating components.
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Terms in Enzyme Chemistry
Activation: Any process that initiates or increases the activity of an enzyme.
Inhibition: Any process that makes an active enzyme less active or inactive.
Competitive inhibitor: A substance that binds to the active site of an enzyme thereby preventing binding of substrate.
Noncompetitive inhibitor: Any substance that binds to a portion of the enzyme other than the active site and thereby inhibits the activity of the enzyme.
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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 affected by:– Enzyme concentration.– Substrate concentration. – Temperature.– pH.
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The effect of enzyme concentration on the rate
Substrate concentration, temperature, and pH are constant.
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The effect of substrate concentration on the rate
Enzyme concentration, temperature, and pH are constant.
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The effect of temperature on the rate
Substrate and enzyme concentrations and pH are constant.
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The effect of pH on the rate Substrate and enzyme concentrations and temperature are
constant.
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Lock-and-key model- The enzyme is a rigid three-dimensional body.– The enzyme surface contains the active site.
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Induced FitThe active site becomes modified to accommodate the
substrate.
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Competitive InhibitionWhen a competitive inhibitor enters the active site, the substrate
cannot enter.
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Noncompetitive InhibitionThe inhibitor binds itself to a site other than the active site (allosterism), thereby changing the conformation of the active site. The substrate still binds but there is no catalysis.
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Enzyme kinetics in the presence and the absence of inhibitors.
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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 site in more than 65% of the enzymes studied to date.
– These five are His > Cys > Asp > Arg > Glu.– Four of these amino acids have either acidic or basic
side chains; the fifth has a sulfhydryl group (-SH).
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Catalytic Power• Enzymes provide an alternative pathway for reaction. (a) The
activation energy profile for a typical reaction. (b) A comparison of the activation energy profiles for a catalyzed and uncatalyzed reactions.
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Enzyme RegulationFeedback control: An enzyme-regulation process where the product of a series of enzyme-catalyzed reactions inhibits an earlier reaction in the sequence.
– The inhibition may be competitive or noncompetitive.
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Enzyme Regulation
• Proenzyme (zymogen): An inactive form of an enzyme that must have part of its polypeptide chain hydrolyzed and removed 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 and removed 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.
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Enzyme Regulation
Allosterism: Enzyme regulation based on an event occurring 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
enzyme.
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Enzyme Regulation
• The allosteric effect. Binding of the regulator to a site other than the active site changes the shape of the active site.
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Enzyme RegulationEffects of binding activators and inhibitors to allosteric
enzymes. The enzyme has an equilibrium between the T form and the R form.
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Enzyme RegulationProtein 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).
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Enzyme Regulation
Isoenzyme (Isozymes): 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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Enzyme RegulationThe isozymes of lactate dehydrogenase (LDH). The electrophoresis gel depicts the relative isozyme types found in different tissues.
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Enzymes Used in Medicine
Insert Table 23.2, page 648
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Transition-State Analogs
• Transition state analog: A molecule whose shape mimics the transition state of a substrate.
• Figure 23.17 The proline racemase reaction. Pyrrole-2-carboxylate mimics the planar transition state of the reaction (next screen).
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Transition-State Analog
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Transition-State Analogs• Abzyme: An antibody that has catalytic activity
because it was created using a transition state analog as an immunogen. (a) The molecule below is a transition analog for the reaction of an amino acid with pyridoxal-5’-phosphate. (b) The abzyme is then used to catalyze the reaction on the next screen.
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Transition-State Analogs