8.1 Metabolism

Metabolic Pathways

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

Metabolic chain example

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

Metabolic cycle example

Krebs cycle (in cell respiration) and the Calvin cycle (in photosynthesis)

Activation Energy

The minimum energy required for a chemical reaction to proceed.

Enzyme binds to a substrate + effect

It stresses and destabilizes 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.

Exergonic reaction

When the reactants contain more energy than the products, the free energy is released into the system.

(usually catabolic reactions)

Endergonic reaction

When the reactants contain less energy than the products, free energy is lost to the system.

(Usually anabolic reactions)

Enzyme inhibitor

A molecule that disrupts the normal reaction pathway between an enzyme and a substrate.

Competitive inhibition

Competitive inhibition involves a molecule, other than the substrate, binding to the enzyme's active site.

The 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.

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.

Example competitive inhibitor

Relenza is a synthetic drug designed to treat individuals infected with the influenza virus.

Virions are released from infected cells when the viral enzyme neuraminidase cleaves a docking protein.

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.

Example non-competitive 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 an electron to the final acceptor (oxygen)

Consequently, the electron transport chain cannot continue to function and ATP is not produced via aerobic respiration.

Feedback inhibition (end-product inhibition)

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

What does end-product inhibition do?

The final product in a series of reactions inhibits an enzyme from an earlier step in the sequence

How does end-product inhibition work?

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

Why is end-product inhibition important?

If products levels build, 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 rate of product formation will increase

Example end-product inhibition

Isoleucine is an essential amino acid, meaning it is not synthesized by the body in humans

What food sources include isoleucine (for humans)

Eggs, seaweed, fish, cheese, chicken and lamb.

Isoleucine in plants and bacteria

Isoleucine may be synthesized from threonine in a five-step reaction pathway.

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.

Isoleucine pathway

The effect of inhibition on enzyme kinetics (graph)

Malaria

A disease caused by parasitic protozoans of the genus Plasmodium falciparum

Life cycle of plasmodium falciparum

Requires both a human and a 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.

Proteome

The entire complement of proteins that is or can be expressed by a cell, tissue, or organism.

How were the enzymes involved in malaria identified?

From the proteome

How were the enzymes found in malaria scanned for potential enzyme inhibitors?

Using a bioinformatic database

rational drug design

Involves using computer modelling techniques to invent a compound that will function as an inhibitor