enzyme inhibition Flashcards
Why should a metabolic pathway not be allowed to continue to run without stopping?
build-up of excess product
inefficient in terms of energy usage
Inhibitors
molecules that prevent enzymes from carrying out their normal function or slow them down.
two types of inhibitors:
competitive and non-competitive.
Competitive inhibition
Competitive inhibitors compete with the
substrate for binding at the enzyme’s active
site and their shape closely resembles the
substrate’s.
binds to the active site to form an
enzyme-inhibitor complex and
physically blocks entry for the
substrate.
When the inhibitor leaves the active site, the
substrate can bind as normal and be converted into product.
Non-competitive inhibition
Non-competitive inhibitors do not compete with the substrate for the active site.
They have a completely different shape to the substrate and bind to a different part of the enzyme called the allosteric site.
The binding causes a change in conformation of the active site so that the substrate cannot bind
If the non-competitive inhibitor is a reversible inhibitor, it can dissociate from the allosteric site which will allow the active site’s shape to revert to normal, allowing the substrate to bind.
Reversible and irreversible inhibition
both competitive and non-competitive inhibition, the binding of inhibitor can be reversible or irreversible.
This depends on the strength of the bonds formed.
Hydrogen bonds and ionic bonds are weak and will break easily, allowing the inhibitor to leave (reversible) the active site so that the substrate can bind as normal.
If strong covalent bonds form, the inhibitor cannot be removed, and inhibition is often irreversible
Uses of inhibitors: drugs
antibiotics penicillin and vancomycin inhibit enzymes involved in the production of
bacterial cell walls.
Extracts from purple foxglove leaves used to treat heart failure.
The effect of competitive inhibitors on the rate of reaction
With a fixed amount of competitive inhibitor, the rate of reaction will increase more slowly because the inhibitor and substrate compete for the active site.
Eventually, the substrate overwhelms the inhibitor, and the same maximum rate is reached.
The effect of non-competitive inhibitors on the rate of
reaction
With a fixed amount of non-competitive
inhibitor, the maximum rate of the reaction is much lower.
Increasing the concentration of substrate has no effect on the inhibitor’s ability to bind to the allosteric site.
Inhibitors: Metabolic Poisons
Inhibitors in toxins/venom can irreversibly block enzymes such as acetylcholinesterase (important at neuromuscular synapses), causing paralysis and death.
Heavy metals such as mercury and cadmium are irreversible non-competitive inhibitors blocking a range of metabolic reactions.
End-product inhibition
end-product of a metabolic pathway acts as a regulator of the pathway
When the amount of end-product is high, it binds non-competitively to an enzyme in the pathway, blocking further production of itself.
When the amount of end-product falls, inhibition ends and the pathway restarts.
