Enzyme Inhibitors Flashcards
Control of metabolic activity within cells
Different steps in reaction pathways are controlled by different enzymes. Controlling the activity of enzymes at crucial points in the pathways regulates the rate and quantity of product formation.
Enzymes can be activated with cofactors, or inactivated with inhibitors
What are inhibitors
Molecules that prevent enzymes from carrying out the normal function of catalysis (or slow them down) . There are two types of enzyme inhibitors-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 cannon 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 slow 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, inhibitor and enzyme.
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.
Effects of competitive inhibitors on rate of reaction
A competitive inhibitor reduces the rate of reaction for a given concentration of substrate, but it doesn’t change the V max of the enzyme it inhibits. Of the substrate concentration is increased enough there will be so much more substrate than inhibitor that the original V max can still be reached.
Examples of competitive inhibitors
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.
Non-competitive inhibitors
-The inhibitor binds 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.
Effects of non-competitive inhibitor on rates of reaction
Increasing concentration of enzyme or substrate will not overcome the effect of a non-competitive inhibitor. Increasing the concentration of inhibitor, however, will decrease the rate of reaction further as more active sites become unavailable.
Examples of irreversible non-competitive inhibitors
-Irreversible inhibitors cannot be removed from the part of the enzyme they are attached to. They are often very toxic, but not always. Organophosphates used as insecticides and herbicides irreversibly inhibit the enzyme acetyl cholinesterase, an enzyme necessary for nerve impulse transmission. This can lead to muscle cramps, paralysis and even death if accidentally ingested.
Proton pump inhibitors (PPI) 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 of stomach ulcers.
End-product inhibition
Term used 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.
How does respiration work
Respiration is a metabolic pathway resulting in the production of ATP. Glucose is broken down in a number of steps. The first step involves the addition of two phosphate groups to the glucose molecules.the addition of the second phosphate group, which results in the 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 levels of ATP are high, more ATP binds to the allosteric site on PFK, preventing the addition of the 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 the enzyme is able to catalyse the addition of a second phosphate group to glucose. Respiration resumes, leading to the production of more ATP.
