1. Part 2 INHIBITION ALLOSTERIC REGULATION FEEDBACK INHIBITION
2.5 & 8.1 ENZYMES
Part 2
INHIBITION
ALLOSTERIC REGULATION
FEEDBACK INHIBITION

2. Remember… Enzymes catalyze (speed up) biological reactions
The substrate (the reactants) must bind to the enzyme at the active site.
Enzymes are NOT reactants or products
Enzymes are NOT used up in a reaction
Enzymes may be used over and over again (so long as they have not been denatured)
Enzymes are specific to a particular substrate (or group of substrates)

3. Enzyme Animations

4. Remember…. Enzymes are NOT reactants or products
Enzymes are NOT used up in a reaction
Enzymes may be used again over and over again (so long has they have not been denatured)
Enzymes are specific to a particular substrate (or group of substrates)

7. Cells must control enzyme activity to coordinate cellular activities
This can be done by:
Restricting the production of a particular enzyme (enzymes are proteins, so your body can control how much you make of them)
Inhibiting the action of an enzyme
This may involve
a) competitive inhibition
b) non-competitive inhibition
- including allosteric regulation
c) feedback inhibition

8. ENZYME INHBITION
Sometimes enzyme function can be inhibited by other molecules (reducing the rate of enzyme-controlled reactions)
These molecules are called INHIBITORS
There are COMPETITIVE INHIBITORS and NON-COMPETITIVE INHIBITORS

9. a) Competitive Inhibitors
These are molecules that are similar in shape to the substrate
They bind to the enzyme’s active site preventing the real substrate from binding
The molecule “competes” with the substrate for the active site
This can be overcome by increasing the substrate concentration

10. Competitive Inhibitor
substrate
Now the substrate cannot get to the active site because it is blocked by the inhibitor.
enzyme

11. Ex: PRONTOSIL (competitive inhibitor)
PRONTOSIL – is an antibacterial drug
Bacteria require folic acid for replication of genetic material
Prontosil binds to the enzyme that makes folic acid preventing other substrates from binding
As a result, folic acid is no longer made and the bacterial cell dies
Since animal cells don’t make folic acid themselves, they do not have this enzyme and so Prontosil has no effect on them

12. b) Non-competitive Inhibition
A molecule binds to the enzyme at a location other than the active site
This binding alters the shape of the enzyme, changing the shape of the active site
The enzyme is now dysfunctional because the substrate now cannot bind to the active site.
Adding more substrate will not affect the reaction because the active site is unavailable.

13. Non competitive inhibitor
substrate
Non competitive inhibitor
The shape of the active site has changed
Therefore, the substrate no longer fits in
enzyme

14. Ex: Cytochrome C Oxidase (non-competitive inhibition)
Regular Function
Speeds up the reduction of oxygen to water in cellular respiration
Without it, the reaction will not occur fast enough and the organism will die because not enough energy is released.

15. Ex: Cytochrome C Oxidase (non-competitive inhibition)
CN- attach to the –SH groups in the enzyme
This destroys the disulfide bridges and thus changing the tertiary structure of the enzyme
Change in the shape results in the change in the active site thus the substrate cannot bind and cytochrome c oxidase is now non-functional.

16. Animations

17. Competitive Inhibitor
When there is more substrate than inhibitor, the max. rate of reaction can be reached. However, it takes a larger substrate concentration to reach maximum rate of reaction.

18. Non-competitive Inhibitor
Has a much lower maximum rate of reaction
It takes approximately the same concentration of substrate to reach the maximum rate of reaction.

19. Allosteric Regulation
Some enzymes have receptor sites away from the active site called ALLOSTERIC SITES
(These enzymes are usually proteins made of several subunits each with an active site)
Substance that bind to the allosteric sites may inhibit or stimulate (increase) the enzyme activity.

20. Allosteric Regulation - Activators
Binding an ACTIVATOR to an allosteric site stabilizes the protein conformation
This keeps all the active sites available for the substrates to bind to them.

21. Allosteric Inhibition
Binding of an allosteric inhibitor (a type of non-competitive inhibitor) stabilizes the inactive form of the enzyme

22. Allosteric Regulation
The binding of an activator or an inhibitor affects the activity of all the active sites on the enzyme

23. Metabolic Pathways
These are chains and cycles of enzyme-catalyzed reactions
Most chemical reactions do not happen in one large step, but rather as a sequence of smaller steps/reactions
The product of the 1st enzyme catalyzed reaction is the substrate for the 2nd enzyme catalyzed reaction.

24. Metabolic Pathways

25. Metabolic Pathways
Metabolic reactions can be either a chain of reactions or a cycle.
In a cycle, the end product is substrate for the first enzyme and it will start the pathway again.

26. c) Feedback Inhibition
Method of controlling metabolic pathways
Negative feedback inhibition is like a thermostat.
When it is cold, the thermostat turns on the heater to produce heat.
When it is too warm, the heat will cause the thermostat to turn off the heater

27. Feedback Inhibition Cold Thermostat Heater Heat
INHIBITS
Heat has a negative effect on the thermostat;
A build up of product inhibits the enzymes and the reaction: NEGATIVE FEEDBACK

28. Feedback Inhibition
Many enzymatic pathways are regulated by feedback inhibition
As the enzyme’s end product accumulates, it inhibits the enzyme by binding to the first enzyme in the pathway.
This shuts down the entire sequence.

29. Example
Through a series of 5 reactions, the amino acid threonine is converted into isoleucine
As the concentration of isoleucine builds up, it binds to the allosteric site of the 1st enzyme (threonine deaminase), acting as a non-competitive inhibitor.

32. Feedback Inhibition
As the product is used up over time, the concentration of product decreases
The inhibition product will detach from the enzyme allowing it to become active once again and produce product.
When the product concentration gets too high again, the product will once again allosterically inhibit the enzyme

33. Animations Feedback inhibition animation (text)