1. Enzymes Notes #2- Enzyme Substrate Complexes and Factors Affecting Enzymes

2. Agenda Sign up for rewrite if you want to take it (today is last day)
Video
Notes
Short Video
Group Activity
Planning and presentation
Practice

3. Video

4. Enzymes
Catalysts are substances that speed up chemical reactions.  Organic catalysts (contain carbon) are called enzymes.
Enzymes are specific for one particular reaction or group of related reactions.
Many reactions cannot occur without the correct enzyme present.
They are often named by adding “ASE" to the name of the substrate. Example: Dehydrogenases are enzymes that remove hydrogen.

5. Enzyme-Substrate Complexes
When a substrate binds to the active site of an enzyme it is said form a complex.
The original theory on how this worked was called the LOCK and KEY model
This was because the substrate shape fits into a specific enzyme because of it’s shape like a specific key fits only a specific lock

6. Lock and Key Model
As the substrates bind to the enzyme active site they are brought closer together allowing the reaction to occur
Sometimes the active site changes shape to bring the substrates even closer together
The reaction occurs and the product(s) are released. The enzyme returns to it’s normal tertiary configuration

7. Induced Fit Theory – Most current
“Induced-Fit model” is very similar but it claims that the enzyme has the ability to slightly alter its shape. The two models basically work the same way.
The substrate molecule does not fit exactly in the active site. This induces a change in the enzymes conformation (shape) to make a closer fit.
After the reaction, the products are released and the enzyme returns to its normal shape.
Only a small amount of enzyme is needed because they can be used repeatedly.

9. Video

10. Roles of Enzymes
Some enzymes simply complex with substrates bringing them close together to react
Other enzymes participate in the reaction occuring:
Example: Trypsin
Trypsin digests protein by breaking peptide bonds
Active site contains 3 amino acids with R groups that interact with the peptide bonds
Breaks the bond and brings in water

11. Rate of Reaction
Reactions with enzymes are up to 10 billion times faster than those without enzymes.
Enzymes typically react with between 1 and 10,000 molecules per second. Fast enzymes catalyze up to 500,000 molecules per second.
Substrate concentration, enzyme concentration, Temperature, and pH  affect the rate of enzyme reactions.

12. Group Activity 6 groups: Substrate concentration Temperature pH
Enzyme concentration
Competitive inhibitor
-non-competitive inhibitor (and heavy metals)
Use page 108/109 and handout to prepare presentation
What is it?
Why/How does it impact speed of reaction
Key characteristics
Use a diagram…

13. Substrate Concentration
At lower concentrations, the active sites on most of the enzyme molecules are not filled because there is not much substrate.  Higher concentrations cause more collisions between the molecules.  With more molecules and collisions, enzymes are more likely to encounter molecules of reactant.
The maximum velocity of a reaction is reached when the active sites are almost continuously filled. Increased substrate concentration after this point will not increase the rate.  Reaction rate therefore increases as substrate concentration is increased but it levels off.
Enzyme Active Site is Saturated
Rate of Reaction
Substrate Concentration

14. Enzyme Concentration
If there is insufficient enzyme present, the reaction will not proceed as fast as it otherwise would because there is not enough enzyme for all of the reactant molecules.
As the amount of enzyme is increased, the rate of reaction increases. If there are more enzyme molecules than are needed, adding additional enzyme will not increase the rate. Reaction rate therefore increases as enzyme concentration increases but then it levels off.
Even when adding more enzymes, there isn’t any more available substrate to create product at a faster rate
Rate of Reaction
Enzyme Concentration

15. Effect of Temperature on Enzyme Activity
Rate of Reaction
Temperature 23

16. Effect of Temperature on Enzyme Activity
Increasing the temperature causes more collisions between substrate and enzyme molecules. The rate of reaction therefore increases as temperature increases.
Effect of Temperature on Enzyme Activity
Rate of Reaction
Temperature 23

17. Effect of Temperature on Enzyme Activity
Enzymes denature when the temperature gets too high. The rate of reaction decreases as the enzyme becomes nonfunctional.
Rate of Reaction
Temperature 23

18. Temperature
Higher temperature causes more collisions between the atoms, ions, molecules, etc. It therefore increases the rate of a reaction – “Turnover Rate”. More collisions increase the likelihood that substrate will collide with the active site of the enzyme.
Above a certain temperature, activity begins to decline because the enzyme begins to denature (unfold).
The rate of chemical reactions therefore increases with temperature but then decreases.
Rate of Reaction
Temperature

19. Denaturation
If the hydrogen bonds within an enzyme are broken, the enzyme may unfold or take on a different shape. The enzyme is denatured.
A denatured enzyme will not function properly because the shape of the active site has changed.
If the denaturation is not severe, the enzyme may regain its original shape and become functional.
The following will cause denaturation:
Heat
Changes in pH
Heavy-metal ions (lead, arsenic, mercury)
Alcohol
UV radiation

20. Effect of pH on Enzyme Activity
Each enzyme has its own optimum pH.
Pepsin Trypsin
Rate of Reaction pH 24

21. pH
Each enzyme has an optimal pH. Pepsin, an enzyme found in the stomach, functions best at a low pH. Trypsin, found in the intestine, functions best at a neutral pH.
A change in pH can alter the ionization of the R groups of the amino acids. When the charges on the amino acids change, hydrogen bonding within the protein molecule change and the molecule changes shape. The new shape may not be effective.
The diagram shows that pepsin functions best in an acid environment. This makes sense because pepsin is an enzyme that is normally found in the stomach where the pH is low due to the presence of hydrochloric acid. Trypsin is found in the duodenum (small intestine), and therefore, its optimum pH is in the neutral range to match the pH of the duodenum.
Pepsin Trypsin
Rate of Reaction pH

22. Regulation of Enzymes
The next several slides illustrate how cells regulate enzymes. For example, it may be necessary to decrease the activity of certain enzymes if the cell no longer needs the product produced by the enzymes.

23. Regulation of Enzymes genetic regulation of enzymes regulation
Cell can turn on DNA genes to build more enzymes when needed
genetic
regulation
regulation of enzymes
already produced
Cells can use certain chemicals to slow down existing enzymes
competitive
inhibition
noncompetitive
Inhibition
(next slide) 29

24. Competitive Inhibition
In competitive inhibition, a similar-shaped molecule competes with the substrate for active sites. 27

25. Competitive Inhibition
This substrate cannot get into active site at this time
Active site is being occupied by competitive inhibitor 28

26. Noncompetitive Inhibition
Active site
Inhibitor
Altered active site
Enzyme
Another form of inhibition involves an inhibitor that binds to an allosteric site of an enzyme.  An allosteric site is a different location than the active site.
The binding of an inhibitor to the allosteric site alters the shape of the enzyme, resulting in a distorted active site that does not function properly.

27. Noncompetitive Inhibition
The binding of an inhibitor to an allosteric site is usually temporary.   Poisons are inhibitors that bind irreversibly. For example, penicillin inhibits an enzyme needed by bacteria to build the cell wall. Bacteria growing (reproducing) without producing cell walls eventually rupture.

28. Agenda Homework Check Assignment Answer Review Quiz Video Notes
Demo Activity
Review Worksheet

29. Video

30. A B C D Feedback Inhibition
The goal of this hypothetical metabolic pathway is to produce chemical D from A.
A B C D
enzyme 1
enzyme 2
enzyme 3
B and C are intermediates.
The next several slides will show how feedback inhibition regulates the amount of D produced.
Enzyme regulation by negative feedback inhibition is similar to the thermostat example. As an enzyme's product accumulates, it turns off the enzyme just as heat causes a thermostat to turn off the production of heat. 34

31. X X A B C D X Feedback Inhibition
C and D will decrease because B is needed to produce C and C is needed to produce D. X
The amount of B in the cell will decrease if enzyme 1 is inhibited.
A B C D X
enzyme 1
enzyme 2
enzyme 3
Enzyme 1 is structured in a way that causes it to interact with D. When the amount of D increases, the enzyme stops functioning. 35

32. A B C D B X X X C D Feedback Inhibition
B, C, and D can now be synthesized.
A B C D B X X X C D
enzyme 1
enzyme 2
enzyme 3
When the amount of D drops, enzyme 1 will no longer be inhibited by it. 39

33. A B C D X Feedback Inhibition enzyme 1 enzyme 2 enzyme 3
As D begins to increase, it inhibits enzyme 1 again and the cycle repeats itself. 42

34. Thyroxin and It’s Role in Metabolic Rate
Thyroxin: (AKA “Thyroid Hormone” “Thyroxine”)
- Thyroxin is a protein hormone that is secreted into the blood stream by cells of the thyroid gland
- The thyroid gland, which is located in the neck, accumulates iodine in order to produce the thyroxin hormone.
Thyroid Hormone Structure

35. Thyroxin acts by attaching to receptor sites on the surfaces of our body’s cells. When receptor sites are triggered they stimulate other chemicals in the cell to govern the rate at which the cells will consume oxygen. Thyroxin ultimately controls the body’s metabolism.

36. - Thyroxin does not have a target organ; but instead, stimulates most of the cells of the body to metabolize at a faster rate. It does this by increasing the production of respiratory enzymes, as well as stimulating the increase of oxygen uptake.

37. - Thyroxin not only governs metabolic rate but it also helps regulate the growth and development of an individual.
- Thyroglobulin is the storage (precursor) form of Thyroxin. Iodine is required for thyroglobulin to be made. Without the presence of iodine the thyroid gland will increase in size in an effort to produce more Thyroxin.
- Unfortunately, a lack of Iodine in the diet, results in a lack of thyroxin in the body (HYPOTHYROIDISM). This often leads to a condition known as simple goiter.

38. Simple Gloiter
- A simple goiter occurs when the thyroid gland is unable to produce a sufficient amount of Thyroxin, the thyroid cannot meet the metabolic demands of the body.
-The thyroid gland compensates by enlarging, this mechanism will often overcome a mild deficiency of the thyroid hormone.

39. Exophthalmic Goiter (Graves’ disease)
This type of Goiter is not caused by a lack of thyroxin but rather by the excessive production of the thyroid hormone (HYPERTHYROIDISM). –
- This condition is characterized by an enlarged thyroid gland, protrusion of the eyeballs, tachycardia (super fast heart rate) and nervous excitability.

40. Hypothyroidism vs. Hyperthyroidism
Symptoms of Hypothyroidism: Low thyroxin in the blood