8.1 Metabolism Flashcards
What is metabolism?
Metabolism describes the sum total of all reactions that occur within an organism in order to maintain life
What do most chemical reactions result in?
Most chemical changes in a cell result from a series of reactions (pathways), with each step controlled by a specific enzyme
What is the general role of metabolic pathways?
Metabolic pathways allow for a greater level of regulation, as the chemical change is controlled by numerous intermediates
How are metabolic pathways usually organised?
metabolic pathways are typically organised into chains or cycles of enzyme-catalysed reactions
What are examples of metabolic pathways in the form of chains?
Examples of chains: Glycolysis (in cell respiration), coagulation cascade (in blood clotting)
What are examples of metabolic pathways in the form of cycles?
Examples of cycles: Krebs cycle (in cell respiration), Calvin cycle (in photosynthesis)
What is the activation energy?
Every chemical reaction requires a certain amount of energy in order to proceed – this is the activation energy (EA)
How do enzymes speed up the rate of reaction?
Enzymes speed up the rate of a biochemical reaction by lowering the activation energy
What happens to the substrate when an enzyme binds to it?
When an enzyme binds to a substrate it stresses and destabilises the bonds in the substrate
In specific terms, how is the activation energy of an enzyme-substrate reaction lowered?
This reduces the overall energy level of the substrate’s transitionary state, meaning less energy is needed to convert it into a product and the reaction proceeds at a faster rate
What does it mean if an enzymatic reaction is exergonic?
If the reactants contain more energy than the products, the free energy is released into the system (exergonic)
What are examples of exergonic reactions?
These reactions are usually catabolic (breaking down), as energy is released from broken bonds within a molecule
What does it mean if a reaction is endergonic?
If the reactants contain less energy than the products, free energy is lost to the system (endergonic)
What are examples of endergonic reactions?
These reactions are usually anabolic (building up), as energy is required to synthesise bonds between molecules
What is an enzyme inhibitor? (general definition)
An enzyme inhibitor is a molecule that disrupts the normal reaction pathway between an enzyme and a substrate
What types of enzyme inhibitors can there be?
Enzyme inhibitors can be either competitive or non-competitive depending on their mechanism of action
What do enzyme inhibitors prevent?
Enzyme inhibitors prevent the formation of an enzyme-substrate complex and hence prevent the formation of product
Is enzyme inhibition temporary/permenant?
BOTH
Inhibition of enzymes may be either reversible or irreversible depending on the specific effect of the inhibitor being used
- What is the first step of a normal enzyme reaction?
In a normal reaction, a substrate binds to an enzyme (via the active site) to form an enzyme-substrate complex
- What causes an enzyme to bind to a particular substrate?
The shape and properties of the substrate and active site are complementary, resulting in enzyme-substrate specificity
- How does the active site bind with the substrate? Do any changes need to occur?
When binding occurs, the active site undergoes a conformational change to optimally interact with the substrate (induced fit)
- What is the role of the conformational change of the active site?
This conformational change destabilises chemical bonds within the substrate, lowering the activation energy
- What is the result of enzyme-substrate interaction?
As a consequence of enzyme interaction, the substrate is converted into product at an accelerated rate
What does competitive inhibition involve?
Competitive inhibition involves a molecule, other than the substrate, binding to the enzyme’s active site
What is the competitive inhibitor’s relation to the active site?
The molecule (inhibitor) is structurally and chemically similar to the substrate (hence able to bind to the active site)
How does the competitive inhibitor inhibit enzyme activity?
The competitive inhibitor blocks the active site and thus prevents substrate binding
How can the effects of a competitive inhibitor be reduced?
As the inhibitor is in competition with the substrate, its effects can be reduced by increasing substrate concentration
What does non-competitive inhibition involve?
Non-competitive inhibition involves a molecule binding to a site other than the active site (an allosteric site)
What does the binding of a non-competitive inhibitor cause? Where does it bind?
The binding of the inhibitor to the allosteric site causes a conformational change to the enzyme’s active site
How does a non-competitive inhibitor inhibit enzymatic activity?
As a result of this change, the active site and substrate no longer share specificity, meaning the substrate cannot bind
What can mitigate the effects of a non-competitve inhibitor?
NOTHING
As the inhibitor is not in direct competition with the substrate, increasing substrate levels cannot mitigate the inhibitor’s effect
What are the (general) purposes of enzyme inhibition?
Enzyme inhibitors can serve a variety of purposes, including in medicine (to treat disease) and agriculture (as pesticides)
What is an example of a use of a competitive inhibitor?
An example of a use for a competitive inhibitor is in the treatment of influenza via the neuraminidase inhibitor, RelenzaTM
What is an example of a use of a non-competitive inhibitor?
An example of a use for a non-competitive inhibitor is in the use of cyanide as a poison (prevents aerobic respiration)
What is relenza?
Relenza is a synthetic drug designed by Australian scientists to treat individuals infected with the influenza virus
- What is released from infected cells which is harmful?
relenza
Virions are released from infected cells when the viral enzyme neuraminidase cleaves a docking protein (haemagglutinin)
- How does Relenza prevent infected cells from releasing virions?
Relenza competitively binds to the neuraminidase active site and prevents the cleavage of the docking protein
- What is the final result of reflenza treatment?
Consequently, virions are not released from infected cells, preventing the spread of the influenza virus
What is cyanide? What does it do?
- cyanide
Cyanide is a poison which prevents ATP production via aerobic respiration, leading to eventual death
- What does cyanide bind to?
cyanide
It binds to an allosteric site on cytochrome oxidase – a carrier molecule that forms part of the electron transport chain
- Why is cyanide binding to cytochrome oxidase harmful?
By changing the shape of the active site, cytochrome oxidase can no longer pass electrons to the final acceptor (oxygen)
- What is the final result of cyanide binding?
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 is the inhibitor 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
Where the end-product bind to in end-product inhibition?
The product binds to an allosteric site and temporarily inactivates the enzyme (via non-competitive inhibition)
What is the end result of end-product inhibition?
As the enzyme can no longer function, the reaction sequence is halted and the rate of product formation is decreased
What is the purpose of end-product inhibition?
End-product inhibition functions to ensure levels of an essential product are always tightly regulated
What happens if product levels build up?
end-product inhibition
If product levels build up, the product inhibits the reaction pathway and hence decreases the rate of further product formation
What happens if product levels drop?
end-product inhibition
If product levels drop, the reaction pathway will proceed unhindered and the rate of product formation will increase
What is isoleucine?
Isoleucine is an essential amino acid, meaning it is not synthesised by the body in humans (and hence must be ingested)
What are food sources rich in isoleucine?
Food sources rich in isoleucine include eggs, seaweed, fish, cheese, chicken and lamb
How may isoleucine be synthesised in plants and bacteria?
In plants and bacteria, isoleucine may be synthesised from threonine in a five-step reaction pathway
What is the first step in isoleucine synthesis?
In the first step of this process, threonine is converted into an intermediate compound by an enzyme (threonine deaminase)
What can isoleucine bind to?
Isoleucine can bind to an allosteric site on this enzyme and function as a non-competitive inhibitor
What is isoleucine synthesis an example of?
As excess production of isoleucine inhibits further synthesis, it functions as an example of end-product inhibition
What is the purpose of end-product inhibition for isoleucine?
This feedback inhibition ensures that isoleucine production does not cannibalise available stocks of threonine
How can enzyme-catalysed reactions be calculated?
The rate of an enzyme-catalysed reaction can be calculated and plotted according to the time taken for the reaction to proceed
How can the time taken for an enzyme to catalyse a reaction be measured?
The time taken can be measured according to either the amount of product formed or the amount of substrate consumed
What is reaction rate the inverse of?
reaction rate is the inverse of time taken, meaning that the reaction rate is higher when less time is taken (and vice versa)
What formula can be used to calculate the rate of reaction?
The rate of reaction can be calculated according to the following formula:
Rate of reaction (s–1) = 1 / time taken (s)
What are factors that can influence enzyme reactions/
Factors which can influence the rate of an enzyme-catalysed reaction include temperature, pH and substrate concentration
What type of substance can be used to affect the kinetics of an enzyme reaction?
Competitive and non-competitive inhibitors effect the kinetics of an enzyme-catalysed reaction in different ways:
What do competitive and non-competitive inhibitors have in common?
Both reduce the rate of reaction by limiting the amount of uninhibited enzyme available for reaction
Where do competitive inhibitors bind?
Bind directly to the active site and hence exist in direct competition with the substrate
How do increased substrate levels affect enzyme activity with competitive inhibitors?
Increasing substrate levels will increase the likelihood of the enzyme colliding with the substrate instead of the inhibitor
Can the max rate of enzymatic activity be reached with competitive inhibitors?
The maximum rate of enzyme activity (Vmax) can still be achieved, although it requires a higher substrate concentration
Where do non-competitive inhibitors bind?
Bind to an allosteric site and hence do not exist in direct competition with the substrate
How do increased substrate levels affect enzyme activity with non-competitive inhibitors?
Increasing substrate concentrations will not effect the level of inhibition caused by the non-competitive inhibitor
How is the maximum rate of enzymatic activity affected?
The maximum rate of enzyme activity (Vmax) is therefore reduced
What is malaria?
Malaria is a disease caused by parasitic protozoans of the genus Plasmodium
What does a life cycle of a parasite involve?
The life cycle of the parasite requires both a human and mosquito host – hence the disease is transmitted via mosquito bites
What coordinates the growth and maturation of parasites?
The maturation and development of the parasite in both human and mosquito host is coordinated by specific enzymes
How can anti-malarial drugs be developed?
By targeting these enzymes for inhibition, new anti-malarial drugs and medications can be produced
What have scientists done to the plasmodium?
Scientists have sequenced the genome of infectious species of Plasmodium and used it to determine the parasite’s proteome
What can be done with the proteome of plasmodium?
From the proteome, enzymes involved in parasitic metabolism have been identified as potential targets for inhibition
How can inhibitors be found for the enzymes in plasmodium
These enzymes may be screened against a bioinformatic database of chemicals to identify potential enzyme inhibitors
What is done to a compound that looks promising as an inhibitor for malaria?
Once a promising compound is identified, it may be chemically modified to improve its binding affinity and lower its toxicity
What is a way that malaria drugs can be created?
An alternative method by which potential new anti-malarial medications can be synthesised is via rational drug design
What does rational drug design involve?
Rational drug design involves using computer modelling techniques to invent a compound that will function as an inhibitor
What does rational drug design produce?
Using combinatorial chemistry, a compound is synthesised that is complementary to the active site of the target enzyme
