8.1 Flashcards by A T

Metabolism describes the…

sum total of all reactions that occur within an organism in order to maintain life

How well did you know this?

Not at all

Perfectly

Most chemical changes in a cell result from a series of …

reactions (pathways), with each step controlled by a specific enzyme
- Metabolic pathways allow for a greater level of regulation, as the chemical change is controlled by numerous intermediates

How well did you know this?

Not at all

Perfectly

Metabolic pathways are typically organised into…

chains or cycles of enzyme-catalysed reactions

How well did you know this?

Not at all

Perfectly

Examples of chains:

Glycolysis (in cell respiration), coagulation cascade (in blood clotting)

How well did you know this?

Not at all

Perfectly

Examples of cycles:

Krebs cycle (in cell respiration), Calvin cycle (in photosynthesis)

How well did you know this?

Not at all

Perfectly

Every chemical reaction requires a certain amount of energy in order to proceed –

this is the activation energy (EA)

How well did you know this?

Not at all

Perfectly

enzymes role with activation energy

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 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

How well did you know this?

Not at all

Perfectly

Types of Enzymatic Reactions

exergonic and endergonic

How well did you know this?

Not at all

Perfectly

exergonic

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

How well did you know this?

Not at all

Perfectly

energonic

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

How well did you know this?

Not at all

Perfectly

An enzyme inhibitor is…

a molecule that disrupts the normal reaction pathway between an enzyme and a substrate
- Enzyme inhibitors can be either competitive or non-competitive depending on their mechanism of action

How well did you know this?

Not at all

Perfectly

enzyme inhabitation prevent the formation of…

Enzyme inhibitors prevent the formation of an enzyme-substrate complex and hence prevent the formation of product

How well did you know this?

Not at all

Perfectly

inhibition of enzymes may be either…

Inhibition of enzymes may be either reversible or irreversible depending on the specific effect of the inhibitor being used

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Noncompetitive 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

Examples of Enzyme Inhibition

Enzyme inhibitors can serve a variety of purposes, including in medicine (to treat disease) and agriculture (as pesticides)

An example of a use for a competitive inhibitor is in the treatment of influenza via the neuraminidase inhibitor, RelenzaTM
An example of a use for a non-competitive inhibitor is in the use of cyanide as a poison (prevents aerobic respiration)

Relenza

(Competitive Inhibitor)

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)
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

Cyanide

(Noncompetitive Inhibitor)

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

End-product inhibition (or feedback inhibition) is…

a form of negative feedback by which metabolic pathways can be controlled

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

End-product inhibition functions to ensure…

levels of an essential product are always tightly regulated

If product levels build up, the product inhibits the reaction pathway and hence decreases the rate of further product formation
If product levels drop, the reaction pathway will proceed unhindered and the rate of product formation will increase

Isoleucine is an essential amino acid…

meaning it is not synthesised by the body in humans (and hence must be ingested)
- Food sources rich in isoleucine include eggs, seaweed, fish, cheese, chicken and lamb

In plants and bacteria, isoleucine may be synthesised from threonine in a five-step reaction pathway

In the first step of this process, threonine is converted into an intermediate compound by an enzyme (threonine deaminase)
Isoleucine can bind to an allosteric site on this enzyme and function as a non-competitive inhibitor
As excess production of isoleucine inhibits further synthesis, it functions as an example of end-product inhibition
This feedback inhibition ensures that isoleucine production does not cannibalise available stocks of threonine

The rate of reaction can be calculated according to the following formula:

Rate of reaction = 1 / time taken (s)

Factors which can influence the rate of an enzyme-catalysed reaction include

temperature, pH and substrate concentration

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

Competitive Inhibitors

- 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 higher substrate concentration

Noncompetitive Inhibitors

- 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 - The maximum rate of enzyme activity (Vmax) is therefore reduce

Malaria is a disease caused by parasitic protozoans of the genus Plasmodium

The life cycle of the parasite requires both a human and mosquito host – hence the disease is transmitted via mosquito bites The maturation and development of the parasite in both human and mosquito host is coordinated by specific enzymes By targeting these enzymes for inhibition, new anti-malarial drugs and medications can be produced

Scientists have sequenced the genome of infectious species of Plasmodium and used it to determine the parasite’s proteome

From the proteome, enzymes involved in parasitic metabolism have been identified as potential targets for inhibition

These enzymes may be screened against a bioinformatic database of chemicals to identify potential enzyme inhibitors

- Once a promising compound is identified, it may be chemically modified to improve its binding affinity and lower its toxicity - In one particular study, over 300,000 chemicals were screened to identify 19 new chemicals that might function as inhibitors

An alternative method by which potential new anti-malarial medications can be synthesised is via rational drug design

- Rational drug design involves using computer modelling techniques to invent a compound that will function as an inhibitor - Using combinatorial chemistry, a compound is synthesised that is complementary to the active site of the target enzyme