Metabolism: Topic 8.1 Flashcards
Define metabolism
Metabolism describes the sum total of all reactions that occur within an organism in order to maintain life
How does metabolism takes place?
Most chemical changes in a cell result from a series of reactions (pathways), with each step controlled by a specific enzyme
Advantage of metabolic pathway?
Metabolic pathways allow for a greater level of regulation, as the chemical change is controlled by numerous intermediates
Types of metabolic pathways
Metabolic pathways are typically organised into chains or cycles (the end product of one reaction is the reactant that starts the rest of the pathway) of enzyme-catalysed reactions
Examples of chains: Glycolysis (in cell respiration), coagulation cascade (in blood clotting)
Examples of cycles: Krebs cycle (in cell respiration), Calvin cycle (in photosynthesis)
What is activation energy in metabolism?
Every chemical reaction requires a certain amount of energy in order to proceed – this is the activation energy (EA)
What is the main role of enzymes in metabolism? Explain its function in detail (substrates must reach the transition state before it converts into a product)
Enzymes speed up the rate of a biochemical reaction by lowering the activation energy
When an enzyme binds to a substrate it stresses and destabilises the bonds in the substrate
This reduces the overall energy level needed for the substrate to reach its transition state meaning less energy is needed to convert it into a product and the reaction proceeds at a faster rate
What are exergonic enzymatic reactions?
If the reactants contain more energy than the products, the free energy is released into the system (exergonic)
These reactions are usually catabolic (breaking down), as energy is released from broken bonds within a molecule
What are endergonic enzymatic reactions
If the reactants contain less energy than the products, free energy is lost to the system (endergonic)
These reactions are usually anabolic (building up), as energy is required to synthesise bonds between molecules
What is an enzyme inhibitor?
Enzyme inhibitors prevent the formation of an enzyme-substrate complex and hence prevent the formation of product
Types of enzyme inhibitor molecules
Enzyme inhibitors can be either competitive or non-competitive depending on their mechanism of action
Types of enzyme inhibition method
Inhibition of enzymes may be either reversible or irreversible depending on the specific effect of the inhibitor being used. Non-competitive inhibitors lead to an irreversible inhibition to the enzyme and competitive inhibitors lead to a reversible inhibition to the enzyme.
Outline normal enzyme reaction
In a normal reaction, a substrate binds to an enzyme (via the active site) to form an enzyme-substrate complex
The shape and properties of the substrate and active site are complementary, resulting in enzyme-substrate specificity
When binding occurs, the active site undergoes a conformational change to optimally interact with the substrate (induced fit)
This conformational change destabilises chemical bonds within the substrate, lowering the activation energy
As a consequence of enzyme interaction, the substrate is converted into product at an accelerated rate
Outline competitive inhibition
Competitive inhibition involves a molecule, other than the substrate, binding to the enzyme’s active site
The molecule (inhibitor) is structurally and chemically similar to the substrate (hence able to bind to the active site)
The competitive inhibitor blocks the active site and thus prevents substrate binding
As the inhibitor is in competition with the substrate, its effects can be reduced by increasing substrate concentration
Outline non-competitive inhibition
Non-competitive inhibition involves a molecule binding to a site other than the active site (an allosteric site)
The binding of the inhibitor to the allosteric site causes a conformational change to the enzyme’s active site
As a result of this change, the active site and substrate no longer share specificity, meaning the substrate cannot bind
As the inhibitor is not in direct competition with the substrate, increasing substrate levels cannot mitigate the inhibitor’s effect (the rate of reaction will only increase if the enzyme concentration is increased.)
State an example of competitive inhibitor (Relenza)
Relenza is a synthetic drug designed by Australian scientists to treat individuals infected with the influenza virus
Virions are released from infected cells when the viral enzyme neuraminidase cleaves a docking protein (haemagglutinin)(it breaks the binding to the surface receptors of the protein which will then allow it to trigger spread of influenza infection)
Relenza competitively binds to the neuraminidase active site and prevents the cleavage of the docking protein
Consequently, virions are not released from infected cells, preventing the spread of the influenza virus
State example of non-competitive enzyme reaction (cyanide)
Cyanide is a poison which prevents ATP production via aerobic respiration, leading to eventual death
It binds to an allosteric site on cytochrome oxidase – a carrier molecule that forms part of the electron transport chain
By changing the shape of the active site, cytochrome oxidase can no longer pass electrons to the final acceptor (oxygen)
Consequently, the electron transport chain cannot continue to function and ATP is not produced via aerobic respiration
What is end-product inhibition?
End-product inhibition (or feedback inhibition) is a form of negative feedback by which metabolic pathways can be controlled
What happens in end-product inhibition?
In end-product inhibition, the final product in a series of reactions inhibits an enzyme from an earlier step in the sequence
The product binds to an allosteric site and temporarily inactivates the enzyme (via non-competitive inhibition)
As the enzyme can no longer function, the reaction sequence is halted and the rate of product formation is decreased
What condition is required for end-product inhibition to take place and for the reversal of this process to occur?
When present in higher concentrations, the end product binds with the allosteric site of the first enzyme, thus bringing about inhibition.
Lower concentrations of the end product result in fewer bindings with the allosteric site of the first enzyme, and, therefore, activation of the enzyme.
What is the main purpose of end-product inhibition?
End-product inhibition functions to ensure levels of an essential product (which occurs at the intermediates of the metabolic pathway) are always tightly regulated
If end-product levels build up, the product inhibits the reaction pathway and hence decreases the rate of further essential product formation
If end-product levels drop, the reaction pathway will proceed unhindered and the rate of essential product formation will increase
Competitive and non-competitive inhibitors effect the kinetics of an enzyme-catalysed reaction in different ways:
Both reduce the rate of reaction by limiting the amount of uninhibited enzyme available for reaction
How competitive inhibitors affects enzyme kinetics?
Bind directly to the active site and hence exist in direct competition with the substrate
Increasing substrate levels will increase the likelihood of the enzyme colliding with the substrate instead of the inhibitor
The maximum rate of enzyme activity (Vmax) can still be achieved, although it requires a much higher substrate concentration
How non-competitive inhibitors affects enzyme kinetics?
Bind to an allosteric site and hence do not exist in direct competition with the substrate
Increasing substrate concentrations will not effect the level of inhibition caused by the non-competitive inhibitor (because there is a limited amount of enzymes still active)
The maximum rate of enzyme activity (Vmax) is therefore reduced
