Control of Metabolic Pathways

LO: How is metabolism controlled by enzymes?

Starter: Mind map everything you can recall about enzymes

Enzymes

• Enzymes are biological catalysts that are made of protein and speed up the rate of chemical reactions in a cell.

​

• As metabolism is a series of biochemical reactions, enzymes control the rate of a metabolic pathway.

Enzymes Embedded in the Membrane

Some proteins embedded in the membrane act as enzymes to catalyse different steps in metabolic processes.

​

e.g. the enzyme ATP synthase, which catalyses the formation of ATP in mitochondria, chloroplasts and prokaryotes.

https://www.youtube.com/watch?v=qgVFkRn8f10

The Need for Enzymes

• What are enzymes made of?

​

• Enzymes are specific – describe what this means.

​

• Draw and label an enzyme and substrate fitting together. Label the active site.

Whiteboards!

The Need for Enzymes

All reactions need an initial input of energy (can be small or can be large) called the __________ ________.

​

Energy is required to initially break the bonds in the reactants to form a product.

​

Activation Energy

1 = activation energy with no enzyme

​

2 = activation energy with enzyme

Enzymes lower the activation energy which means reactions can take place at a lower temperature. This means that reactions are able to proceed rapidly at relatively low temperature (body temperature)

The Need for Enzymes

The active site is used to bind to the substrate.

​

This allows the activation energy to be lower as it holds the substrate in the right position for a reaction to take place.

Substrate

Active Site

Enzyme

Orientation of Reactants

When the reaction involves two (or more) substrates, the shape of the active site helps orientate the reactants in the right position so a reaction can take place.

Induced Fit

• The active site is not a rigid structure, it is flexible.

​

• When the substrate enters the active site, the enzyme molecule and the active site change slightly making the active site fit very closely round the substrate molecule.

Induced Fit

The induced fit ensures that the active site comes into very close contact with the molecules of substrate and increases the chance of a reaction taking place.

Orientation of Reactants

• The active site holds the reactants together in an induced fit.
• The chemical bonds in the reactants are weakened, the activation energy is reduced.
• The products now have a low affinity for the active site and are released from the active site
• The enzyme is free to repeat the process.

• Substrates have a high affinity for the active site.

​

• After a reaction, products have a low affinity for the active site.

The affinity of a molecule is the tendency for it to bind to an enzyme

Metabolic Pathways

• In most biochemical reactions, it is not possible to build up or break down molecules in just one step.

​

• A series of steps is a metabolic pathway.

The product of one enzyme reaction can become a substrate for the next enzyme reaction.

​

Remember, enzymes are proteins! Which means a mutation can lead to a faulty enzyme being produced, potentially disrupting this pathway

Disruption to an Enzyme in a Metabolic Pathway

Phenylketonuria (PKU)

Phenylalanine

Tyrosine

Melanin & other metabolites

Enzyme X

• PKU is caused by a genetic mutation.

​

• Enzyme X is mutated and the amino acid Phenylalanine cannot be metabolised.

​

• High levels of Phenylalanine can damage the brain resulting in learning disabilities, behavioural difficulties and epilepsy.

​

• Sufferers must eat a very low protein diet.

PKU-Current Screening Programmes

In the UK decisions are made on whether to screen for a particular disease based upon the long term cost.

​

​

While the precise number of conditions that are screened for vary throughout the UK, broadly they consist of Down syndrome, neural tube defects, sickle cell disease, thalassaemia, phenylketonuria (PKU), congenital hypothyroidism, cystic fibrosis and medium-chain acyl-CoA dehydrogenase deficiency (MCADD).

Do you think this is right?

Screening for PKU (all numbers based upon data from the 1970s).

1 in 15,000 babies in the UK is affected by PKU. The cost to screen per 15,000 babies and provide a lifelong specialised diet for the individual was estimated to be £20,000. If babies with PKU are treated early then much damage can be prevented.

The cost of looking after an untreated child through their 45 year lifespan costs around £126,000.

Why was screening financially the best option?

Look at the pathway below. It shows compounds X, Y and Z and their metabolic pathways

• Which enzymes are essential for the pathway to run from X to Z?

​

• Metabolite C is toxic if it builds up. Why is this not a problem?

​

• A build up of Z inhibits enzyme 1. Why is this useful?

​

1 & 2

Enzyme 7 can reverse if blocked at 8, and go through metabolite D

The cell does not use energy producing something it does not need.

Testing your knowledge

• Give THREE reasons why enzymes are referred to as biological catalysts. (3)

​

• a) What determines the structure of an enzymes’s active site? (1)

b) What is meant by the affinity of substrate molecules for an enzymes’s active site? (1)

c) What term means ‘the change in sharpe of an active site to enable it to bind more snugly to the substrate’? (1)

d) In the following sentences choose the correct answer from each underlined choice.

The shape of the active site ensures that the reactants are correctly orientated/denatured so that the reaction can take place. This is made possible by the fact that the enzyme increases/decreases the activation energy needed by the reactants to reach the transitory/transition state.(3)

​

• a) What is meant by the term rate of reaction? (1)

​

Answers

• They lower the activation energy needed for the chemical reaction to proceed. They speed up the reaction. They remain unchanged at the end of the reaction.
• a) The chemical structure of th protein of which the enzyme is made and the bonding between its compost amino acids.

b) the attraction between the substrate and the active site

c) induced fit

d) orientated decreases transition

• a) Quantity of chemical change that occurs per unit time.

b) i) Initial it causes an increase in rate but at higher concentrations no further increase in rate occurs.

ii) At low concentrations of substrate there are not enough molecules of substrate to occupy all the active sites on the enzymes. At higher concentrations of substrate all the active sites on the enzyme molecules are occupied.

Factors Affecting Enzyme Action

• Describe the effect of temperature on enzyme action. Sketch a graph.

​

• Describe the effect of pH on enzyme action.

​

• What does optimum mean?

​

• What does denature mean?

Whiteboards!

Factors Affecting Enzyme Action

We already know from National 5 that enzyme activity can be affected by temperature and pH.

​

​

Enzyme action can also be affected by an inadequate supply of substrate or the presence of an inhibitor.

Effect of Substrate Concentration on Enzyme Activity

Low concentration – too few substrate molecules present to make use of all the active sites on the enzyme molecules.

​

Increasing substrate leads to an increase in reaction rate as more active sites are involved.

​

Further increase in substrate concentration does not increase rate of reaction further (graph levels off) since all the active sites are occupied.

Checkpoint

• What does ‘affinity for the active site’ mean?

​

• What is the name of the change in shape of the active site to allow it to bind tightly to the substrate?

​

• What effect does an increase in concentration of substrate have on the reaction rate when a limited amount of enzyme is present. Explain why.

Checkpoint

• What does ‘affinity for the active site’ mean?

​

• What is the name of the change in shape of the active site to allow it to bind tightly to the substrate?

​

• What effect does an increase in concentration of substrate have on the reaction rate when a limited amount of enzyme is present. Explain why.

Answers:�1) The likelihood of the substrate combining with the active site.

​

2) Induced fit.

​

3) Initially it causes an increase in rate but at higher concentrations no further increase in rate occurs.

At low concentrations of substrate there are not enough molecules of substrate to occupy all the active sites on the enzymes. At higher concentrations of substrate all the active sites on the enzyme molecules are occupied.

�Control of Metabolic Pathways by Enzyme Inhibitors

• Enzymes in metabolic pathways can be controlled by enzyme inhibitors.
• Enzyme inhibitors decrease the rate of enzyme controlled reactions.

​

There are 3 types:

• Competitive inhibitor
• Non-Competitive inhibitor
• Feedback inhibitor

�Competitive Inhibitors�

• Similar in structure to the substrate.

​

• Can attach to active site of enzyme.

• How would this change the reaction rate? Explain your answer.

​

• Draw a diagram to demonstrate this.

​

• What could be increased to overcome competitive inhibition?

Competitive Inhibitors

• Competitive inhibitor molecules are similar to the shape of the substrate and compete for the available active site on the enzyme.

​

• The active sites are now blocked, substrate molecules cannot bind, preventing the substrate from entering - reducing reaction rate.

​

• Inhibition can be overcome by increasing substrate concentration.

�Non-Competitive Inhibitors�

Doesn’t bind to active site, instead they bind to another place on the enzyme (allosteric site).

​

Changes the shape of the active site.

• How would this change the reaction rate? Explain your answer.

​

• Draw a diagram to demonstrate this.

​

• What effect would increasing substrate concentration have on reaction rate?

Non-Competitive Inhibitors

• Non-competitive inhibitors bind to another part of the enzyme (allosteric site) and indirectly affects the shape of the active site, preventing the enzyme from entering.

​

• This cannot be overcome with increasing substrate concentration.

Inhibitors and Enzyme Reactions

Line 1 = no inhibitor

​

• Which line represents competitive inhibitor?

​

• Which line represents non-competitive inhibitor?

2

3

Inhibitors and Enzyme Reactions

• In line 1, why does the rate of reaction become constant rather than continue increasing?

​

• For line 2, explain why there is a continual increase in reaction rate.

​

• For line 3, explain why increasing substrate concentration has no effect on reaction rate.

Inhibitors and Enzyme Reactions

• In line 1, why does the rate of reaction become constant rather than continue increasing?

All the active sites are occupied by substrate

• For line 2, explain why there is a continual increase in reaction rate.

Increasing substrate concentration means it is more likely that the substrate will occupy the active site than the inhibitor.

• For line 3, explain why increasing substrate concentration has no effect on reaction rate.

​

Increasing the substrate concentration in the presence of inhibitors

Because the active site has changed shape, no matter how much we increase the concentration of the substrate, none of them can bind to the newly changed active site. This means that there is no way to reverse the effect of non-competitive inhibitors

Competitive inhibitors’ effect can be reversed by increasing substrate concentration - increasing the reaction rate

Normal enzyme activity levels off after all the substrates have binded with an active site.

1a) What property of a competitive inhibitor enables it to compete with the substrate? (1)

​

Bi) What effect does an increase in concentration of a substrate have on the rate of a reaction with a limited amount of competitive inhibitor and enzyme present? (1)

​

B ii) Explain why? (2)

​

2) The diagram shows a metabolic pathway where the metabolites P, Q and R are present in equal quantities at the start.

​

​

​

​

​

• Name enzyme X’s i) Substrate ii) Product (2)

​

• Name enzyme y’s i) Substrate ii) Product (2)

​

• In which direction will the pathway proceed if more of metabolite P is added to the system.

Answers

• 1a. It’s molecular shape is similar to that of the substrate (1)
• Bi) It brings about an increase in the rate of the reaction. (1)
• Ii) Substrate molecules eventually out number those of the competitive inhibitor causing more site on the enzyme to be occupied with the substrate. (2)
• 2ai) P ii) Q
• B i) Q ii) R
• C) Left to right

​

Give an account of enzyme action and enzyme inhibition. 8