1. 8.1 Metabolism
Essential idea: Metabolic reactions are regulated in response to the cell’s needs.

2. 8.1 Metabolism
Nature of science: Developments in scientific research follow improvements in computing—developments in bioinformatics, such as the interrogation of databases, have facilitated research into metabolic pathways. (3.8)
Understandings:
Metabolic pathways consist of chains and cycles of enzyme-catalyzed reactions
Enzymes lower the activation energy of the chemical reactions that they catalyze
Enzyme inhibitors can be competitive or non-competitive
Metabolic pathways can be controlled by end-production inhibition

3. 8.1 Metabolism Applications and Skills:
Application: End-production inhibition of the pathway that converts threonine to isoleucine
Application: Use of databases to identify potential new anti-malarial drugs
Skill: Calculating and plotting rates of reaction from raw experimental results
Skill: Distinguishing different types of inhibition from graphs at specified substrate concentration

4. U 8.1.1 Metabolic pathways consist of chains and cycles of enzyme-catalyzed reactions
Metabolism was introduced in the 19th century by Theodor Schwann
It was referred to the chemical changes that occur in living things
Metabolism is more complex than this but it has 3 common pattern

5. 1. Most chemical changes happen in sequences of small steps
1. Most chemical changes happen in sequences of small steps. This is called a metabolic pathway
Example from text book:
TREAD initial substrate
BREAD
BREED
BLEED intermediates
BLEND
BLIND
BLINK final product

6. 2. Most metabolic pathways involve a chain of reactions

7. 3. Some metabolic pathways form a cycle

8. U 8.1.2 Enzymes lower the activation energy of the chemical reactions that they catalyze
Substrates need to pass through a transition state before being converted to the final product
Energy is needed for this transitional state
This is the activation energy
Activation energy is the energy needed to get the reaction going and is needed to break or weaken bonds

9. Reactions without an enzyme

10. Reactions with enzymes
An enzyme helps to lower the activation energy
When a substrate binds to the active site it will be altered to reach the transitional state and then converted to the product
This will happen with a lot less energy input needed with the use of an enzyme
It will also happen at a faster rate
The net amount of energy released by the reaction is not changed by the enzyme

11. Reactions with enzymes

12. U 8.1.3 Enzyme inhibitors can be competitive or non-competitive
Inhibitors bind to enzymes and reduce their activity
There are two main types of inhibitors: competitive and non- competitive
Competitive inhibitors interfere with the active (binding) site
This prevents the substrate from binding
Non-competitive inhibitors bind to another site on the enzyme
This causes the enzyme to change shape so the substrate cannot bind

13. Competitive inhibition

14. Non-competitive inhibition

15. S Distinguishing different types of inhibition from graphs at specified substrate concentration
Normal (purple)- no inhibitor
Competitive (green)- when the concentration of substrate begins to exceed the amount of inhibitor the max rate will be achieved. A much higher concentration of substrate is needed
Noncompetitive (blue)- enzyme will not reach max

16. U 8.1.4 Metabolic pathways can be controlled by end-production inhibition
An allosteric site is a special site on an enzyme that a chemical substance can bind to
Normally the chemical substance that binds to the allosteric site is the end product of the pathway
These are called allosteric interactions
The end product acts as an inhibitor
Example: ATP and phosphofructokinase

17. This is a very economical way to control metabolic pathways
Reactions normally do not go to completion but instead reach equilibrium
If there is an increase of products made and equilibrium shifts then the reaction will slow down or stop
End-product inhibition prevents build ups of intermediates

18. A 8.1.1 End-production inhibition of the pathway that converts threonine to isoleucine
Threonine is converted to isoleucine in five reactions
As the concentration of isoleucine increases it binds to an allosteric site of the first enzyme in the pathway threonine deaminase
It acts as a non-competitive inhibitor

20. A 8.1.2 Use of databases to identify potential new anti-malarial drugs
Malaria is caused by the pathogen Plasmodium falciparum
Symptoms include fever, chills, and sweating and is spread by mosquitos
Malaria is becoming resistance to anti-malaria drugs such as chloroquine
The genome for P. falciparum strain 3D7 has been sequenced
Scientists are screening chemicals against 3D7 and another strain K1 to see if they inhibit metabolism
One study identified 19 new chemicals that inhibit enzymes targeted by anti-malarial drugs and 15 chemicals that bind to 61 different malarial proteins
This will help in the development of new malarial drugs

21. S 8.1.1 Calculating and plotting rates of reaction from raw experimental results
Determining the rate of an enzyme-controlled reaction involves measuring either:
The rate of disappearance of the substrate
The rate of appearance of the product