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

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

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

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

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

2. Most metabolic pathways involve a chain of reactions

3. Some metabolic pathways form a cycle

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

Reactions without an enzyme

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

Reactions with enzymes

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

Competitive inhibition

Non-competitive inhibition

S 8.1.2 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

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

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

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

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

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