Chapter 4- 4.3- Enzyme inhibitors Flashcards
Why is it important that cellular conditions such as pH and temperature are kept within narrow limits ?
So that enzyme activity is not delayed. This ensures the reactions can happen at a rate fast enough to sustain living processes, e.g respiration.
How can enzymes be activated and inactivated?
Activated by cofactors and inactivated by inhibitors.
What are inhibitors?
Molecules that prevent enzymes from carrying out their normal function of catalysis ( or slow them down).
What are the two types of enzyme inhibition?
Competitive and non-competitive
How does competitive inhibition work?
- a molecule or part of a molecule that has a similar shape to the substrate of an enzyme can fit into the active site of the enzyme.
- this blocks the substrate from entering the active site, preventing the enzyme from catalysing the reaction.
- the enzyme cannot carry out its function and is said to be inhibited.
- the non-substrate molecule that binds to the active site is a type of inhibitor.
- substrate and inhibitor molecules present in a solution will compete with each other to bind to the active sites of the enzymes catalysing the reaction.
This will reduce the number of substrate molecules binding to active sites in a given time and slows down the rate of reaction.
For this reason such inhibitors are called competitive inhibitors and the degree of inhibition will depend on the relative concentrations of substrate, inhibitors, and enzymes.
Is the effect of competitive inhibitors reversible?
Yes, most competitive inhibitors only bind temporarily to the active site of the enzyme, so their effect is reversible. However there are some exceptions such as aspirin.
Why is it important that reactions do not happen too fast ?
Could lead to a build up of excess products.
A competitive inhibitors reduces the rate of reaction for a given concentration of substrate but what does it not change ?
The V(max) of the enzyme it inhibits. If the substrate concentration is increased enough there will be so much more substrate than inhibitor that the original V(Max) can still be reached.
What are 2 examples of competitive inhibition?
Statins are competitive inhibitors of an enzyme used in the synthesis of cholesterol. Statins are regularly prescribed to help people reduce blood cholesterol concentration. High blood cholesterol levels can result in heart disease.
Aspirin irreversibly inhibits the active site of COX enzymes, preventing the synthesis of prostaglandins and thromboxane, the chemicals responsible for producing pain and fever.
How do non-competitive inhibitors work?
- the inhibitors bind to the enzyme at a location other than the active site. This alternative site is called an allosteric site.
- the binding of the inhibitor causes the tertiary structure of the enzyme to change, meaning the active site changes shape.
- this results in the active site no longer having a complementary shape to the substrate so it is unable to bind to the enzyme.
- the enzyme cannot carry out its function and it is said to be inhibited.
As the inhibitor does not compete with the substrate for the active site it is called a non-competitive inhibitor.
Will increasing the concentration of enzyme or substrate overcome the effect of a non-competitive inhibitor?
No. Increasing the concentration of inhibitors however will decrease the rate of reaction further as more active sites become unavailable.
What are examples of non-competitive inhibitors?
The binding of the inhibitor may be reversible or non-reversible.
Irreversible inhibitors cannot be removed from the part of the enzyme they are attached to. They are often very toxic, but not always.
Organophosphate used as insecticides and herbicides irreversibly inhibit the enzyme acetyl cholinesterase, an enzyme necessary for nerve impulse transmission. This can lead o muscle cramps, paralysis, and even death if accidentally ingested.
Proton pump inhibitors (PPIs) are used to treat long-term indigestion. They irreversibly block an enzyme system responsible for secreting hydrogen ions into the stomach. This makes PPIs very effective in reducing the production of excess acid which, if left untreated, can lead to formation to formation of stomach ulcers.
What is meant by the term end-product inhibition?
It is the term for enzyme inhibition that occurs when the product of a reaction acts as an inhibitor to the enzyme that produces it.
This serves as a negative feedback control mechanism for the reaction. Excess products are not made and resources are not wasted.
It is an example of non-competitive reversible inhibition.
Respiration is a metabolic pathway resulting in the production of what?
Example of end-product inhibition.
ATP.
Glucose is broken down in a number of steps.
The first step involves the addition of two phosphate groups to the glucose molecule.
The addition of the second phosphate group, which results in initial breakdown of the glucose molecule, is catalysed by the enzyme phosphofructokinase (PFK).
This enzyme is competitively inhibited by ATP. ATP therefore regulates its own production.
When the levels of ATP are too high, more ATP bind to the allosteric site of PFK, preventing the addition of a second phosphate group to glucose. Glucose is not broken down and ATP is not produced at the same rate.
As ATP is used up, less binds to PFK and he enzyme is able to catalyse the addition of a second phosphate group to glucose. Respiration resume, leading to the production of more ATP.
