Lesson 13 - Enzyme inhibitors Flashcards
Why is controlling the activity of enzymes important?
Regulates the rate and quantity of product formation.
Inhibitors:
Molecules that prevent enzymes from carrying out their normal function of catalysis.
Types of enzyme inhibitor?
- Competitive
- Non-competitive
Competitive inhibition: draw graph
https://uk.images.search.yahoo.com/search/images;_ylt=AwrIe0V0TpFn7wIAtWEM34lQ;_ylu=Y29sbwNpcjIEcG9zAzEEdnRpZAMEc2VjA3BpdnM-?p=competitive+inhibitor+graph&fr2=piv-web&type=E210GB384G0&fr=mcafee
Non-competitive inhibitor: graph
uk.images.search.yahoo.com/search/images;_ylt=AwriiaJ3TpFn4UIPS_JNBQx.;_ylu=c2VjA3NlYXJjaARzbGsDYnV0dG9u;_ylc=X1MDMjExNDcxNzAwNQRfcgMyBGZyA21jYWZlZQRmcjIDcDpzLHY6aSxtOnNiLXRvcARncHJpZAN6cC5oeTBrc1JNR2dBbHZzaDZvMFpBBG5fcnNsdAMwBG5fc3VnZwMwBG9yaWdpbgN1ay5pbWFnZXMuc2VhcmNoLnlhaG9vLmNvbQRwb3MDMARwcXN0cgMEcHFzdHJsAzAEcXN0cmwDMzEEcXVlcnkDbm9uLWNvbXBldGl0aXZlJTIwaW5oaWJpdG9yJTIwZ3JhcGgEdF9zdG1wAzE3Mzc1NzYwODM-?p=non-competitive+inhibitor+graph&fr=mcafee&fr2=p%3As%2Cv%3Ai%2Cm%3Asb-top&ei=UTF-8&x=wrt&type=E210GB384G0#id=8&iurl=https%3A%2F%2Fd1uvxqwmcz8fl1.cloudfront.net%2Ftes%2Fresources%2F11770500%2Fd2fbec8e-9e72-4292-bd49-76397a1f7cf6%2Fimage%3Fwidth%3D500%26height%3D500%26version%3D1541280194055&action=close
How do competitive inhibitors work?
- Molecule or part of a molecule has a very 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 solution will compete with each other to bind to the active sites of the enzymes catalysing the reaction. For this reason such inhibitors will depend on the relative concentrations of substrate, inhibitor and enzyme.
Effect of competitive enzymes on the rates of reaction?
Reduces the rate of reaction for a given concentration of substrate, but it does not change the Vmax of the enzyme it inhibits. If the substrate concentration is increased enough there will be so much more substrate than inhibitor that the Vmax can still be reached.
Examples of competitive inhibitors?
Statins - synthesis of cholesterol.
- Regularly prescribed to help people reduce blood cholesterol concentration. High blood cholesterol levels can result in heart disease.
Aspirin - COX enzymes
Aspiring as a competitive inhibitor?
- Irreversibly inhibits the active sites of COX enzymes
- Prevents synthesis of prostaglandins and thromboxane, chemicals responsible for reducing pain and fever.
How does non-competitive inhibition work?
- 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.
Effect of non-competitive inhibitors?
- Increases the concentration of an enzyme or substrate will not overcome the effect of a non-competitive inhibitor.
- Increasing concentration of inhibitor will decrease the rate of reaction further as more active sites become unavailable
Irreversible inhibitors?
- Can be toxic
Eg. - Organophosphates used as insecticides and herbicides irreversibly inhibit the enzyme acetyl cholinesterase. This enzyme is necessary for nerve impulse transmission. Can lead to muscle cramps, paralysis and death.
Proton pump inhibitors (PPIs)
- Treat long-term indigestion
- Irreversibly block an enzyme system responsible for secreting hydrogen ions into stomach.
- reduces production of excess acid. Can lead to the formation of stomach uclers.
Reversible inhibitors
These form weak bonds (e.g. hydrogen or ionic) with the enzyme.
Irreversible inhibitors
These form strong bonds (e.g. covalent) with the enzyme.
End-product inhibition
Product of the reaction acts an an inhibitor to the enzyme that produces it. Negative feedback control mechanism of reaction.
- Excess products not made and resources are not wasted.
- Non-competitive reversible inhibition
How is glucose broken down?
- Addition of two phosphate groups to the glucose molecule
- Addition of 2nd phosphate group results in initial breakdown of glucose molecule. Catalysed by phosphofructokinase (PFK)
- Phosphofructokinase is non-competitively inhibited by ATP. ATP regulates its own production.
Negative feedback of ATP?
- When ATP levels are high, more ATP binds to the allosteric site of RFK, preventing the addition of the second phosphate group to glucose. Glucose is not broken down and ATP is not produced at the same rate.
- ATP is used up, so less binds to Phosphofructokinase (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.
