Competitive Inhibition in Enzyme Catalysis

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Questions and Answers

What is a characteristic of uncompetitive inhibitors?

They bind to the enzyme-substrate complex. (correct)

They can be overcome by increasing the substrate concentration.

They are more effective at low substrate concentrations.

They are more common than competitive inhibitors.

What is the purpose of designing drugs that mimic the transition state of an enzyme-catalysed reaction?

To mimic the substrate or product.

To increase the substrate concentration.

To bind more strongly to the enzyme. (correct)

To inhibit the enzyme's activity.

What is the result of renin inhibitors blocking the synthesis of angiotensin I and II?

Decreased blood pressure. (correct)

Unchanged blood pressure.

Increased blood pressure.

No effect on blood pressure.

What is the role of angiotensin II in the body?

To compress blood vessels and retain fluid in the kidneys. Signup and view all the answers

What is the mechanism by which renin inhibitors lower blood pressure?

By inhibiting the synthesis of angiotensin I and II. Signup and view all the answers

What is the purpose of designing transition-state analogues?

To design drugs that bind more strongly to the enzyme. Signup and view all the answers

What is the role of renin in the body?

To hydrolyse a specific peptide bond in angiotensinogen. Signup and view all the answers

What is the result of increasing the substrate concentration in the presence of an uncompetitive inhibitor?

The inhibition is unaffected. Signup and view all the answers

What is a possible reason why drugs with a different skeleton to the substrate can act as competitive inhibitors?

They bind to a combination of binding regions within the active site, some of which are used by the substrate and some of which are not Signup and view all the answers

What type of inhibitors can resemble the product of an enzyme-catalyzed reaction more closely than the substrate?

Competitive inhibitors Signup and view all the answers

What is the mechanism of action of competitive inhibitors that do not compete with the substrate?

They bind to the cofactor binding region Signup and view all the answers

What is a characteristic of irreversible inhibitors?

They form a covalent bond with the enzyme Signup and view all the answers

Why do irreversible inhibitors block the affected enzyme permanently?

They form a covalent bond with a key amino acid in the active site Signup and view all the answers

What type of functional group is commonly found in effective irreversible inhibitors?

Electrophilic group Signup and view all the answers

What happens to the substrate when an irreversible inhibitor binds to the active site?

The substrate is blocked from the active site Signup and view all the answers

Why does increasing substrate concentration not reverse the inhibition of irreversible inhibitors?

Because the inhibitor forms a covalent bond with the enzyme Signup and view all the answers

What is the function of the hydroxyethylene transition-state mimic in Aliskiren?

To mimic the tetrahedral geometry of the reaction intermediate Signup and view all the answers

What is the characteristic of the transition-state inhibitor Aliskiren?

Stable due to the absence of a leaving group Signup and view all the answers

What is the role of the tetrahedral intermediate in enzyme-catalyzed reactions?

It is a short-lived intermediate that forms during the reaction Signup and view all the answers

Which of the following is an example of a transition-state inhibitor?

Aliskiren Signup and view all the answers

What is the function of the two aspartyl residues in enzyme-catalyzed reactions?

They are involved in the formation of a tetrahedral intermediate Signup and view all the answers

What is the mechanism of inhibition of ACE inhibitors?

They bind to the enzyme's active site and inhibit the reaction Signup and view all the answers

What is the mechanism by which clavulanic acid functions?

Irreversible alkylation Signup and view all the answers

What is the bond formed between the enzyme and the suicide substrate?

Covalent bond Signup and view all the answers

What is the name of the enzyme inhibited by clavulanic acid?

Alanine transaminase Signup and view all the answers

What is the outcome of the reaction between the enzyme and the suicide substrate?

Irreversible inhibition of the enzyme Signup and view all the answers

What is the byproduct of the condensation reaction?

Imine Signup and view all the answers

What is the function of the CH3 group in the suicide substrate?

To increase the electrophilicity of the substrate Signup and view all the answers

What is the type of inhibition exhibited by clavulanic acid?

Irreversible non-competitive inhibition Signup and view all the answers

What is the role of the fluorine atom in the suicide substrate?

To increase the electrophilicity of the substrate Signup and view all the answers

What is the outcome of the reaction between the enzyme and the substrate in the absence of the suicide substrate?

Formation of a stable enzyme-substrate complex Signup and view all the answers

What type of inhibitors are converted to irreversible inhibitors by the enzyme-catalysed reaction?

Suicide substrates Signup and view all the answers

What is the purpose of using clavulanic acid in antibacterial medication?

To inhibit the enzyme alanine transaminase Signup and view all the answers

What is the function of Trifluoroalanine in the context of enzyme inhibition?

It is a suicide substrate of alanine transaminase Signup and view all the answers

What is the product of the reaction between pyridoxal phosphate and alanine?

Pyridoxamine monophosphate Signup and view all the answers

What is the role of the enzyme transaminase in the reaction between pyridoxal phosphate and alanine?

It catalyses the reaction between pyridoxal phosphate and alanine Signup and view all the answers

What is the structure of the molecule shown in the figure?

Trifluoroalanine Signup and view all the answers

What is the functional group of the molecule shown in the figure?

Fluoroalkyl Signup and view all the answers

What is the type of inhibition that occurs when a suicide substrate reacts with an enzyme?

Irreversible inhibition Signup and view all the answers

What is the purpose of using transition-state inhibitors?

To inhibit enzyme activity Signup and view all the answers

Study Notes

Competitive Inhibitors

Can bind to a combination of binding regions within the active site, some used by the substrate and some not
Can resemble the structure of the product more closely than the substrate
Some competitive inhibitors bind to the active site but do not compete with the substrate, instead occupying the binding region normally occupied by the cofactor

Irreversible Inhibitors

Bind irreversibly to the active site, forming a covalent bond
Block the substrate from the active site
Increasing substrate concentration does not reverse inhibition
Likely to be similar in structure to the substrate

Transition-state Analogues

Designed to mimic the transition state of an enzyme-catalyzed reaction
Bind more strongly than drugs mimicking the substrate or product
High energy, transient species that cannot be isolated or synthesized
Drug design is based on reaction intermediates closer to transition states than substrates or products
Examples: renin inhibitors, statins, ACE inhibitors, protease inhibitors

Renin Inhibitors

Renin is a protease enzyme responsible for hydrolyzing a specific peptide bond in angiotensinogen to form angiotensin I
Angiotensin I is converted to angiotensin II, which raises blood pressure
Renin inhibitors should act as antihypertensives by preventing the first stage of this process
Examples: aliskiren, which contains a hydroxyethylene transition-state mimic

Suicide Substrates

Agents converted to irreversible inhibitors by the enzyme-catalyzed reaction
React with the target enzyme once formed
Example: trifluoroalanine as a suicide substrate of alanine transaminase
Inhibition mechanism: irreversible alkylation of the enzyme

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Description

Learn about competitive inhibition in enzyme catalysis, where drugs with different skeletons can act as inhibitors by binding to various regions in the active site. Understand how enzyme inhibitors can interact with the active site and affect enzymatic reactions.