Enzyme Inhibitors
Control of metabolic activity within cells
Controlling enzyme activity is essential because it allows cells to regulate the rate and quantity of product being produced.
Enzymes can be activated with cofactors or inactivated with inhibitors. Inhibitors = molecules that prevent enzymes from carrying out their normal function of catalysis (or slowing them down). There are 2 types of enzyme inhibition - competitive and non-competitive
Competitive Inhibition
A molecule or part of a molecule that has a similar shape to the substrate of an enzyme can fit into the active site of the enzyme, blocking substrate from entering the active site, preventing the enzyme from catalysing the reaction.
Therefore enzyme is inhibited as it cant carry out its function
The non substrate molecule that binds to the enzyme = inhibitor.
Substrate and Inhibitor molecules present in solution will compete with each other to bind to the active sites of enzymes. Reducing number of substrate molecules binding to active sites and slow rate of reaction
Therefore called ‘Competitive Inhibitors’. Most only bind temporarily However, some bind permanent such as ‘Aspirin’.
Effects on rates of reaction
Reduces rate of reaction but not Vmax if substrate concentration is increased enough (ratio is too large therefore Vmax still achievable).
Examples of competitive Inhibition
‘Statins’ are competitive inhibitors of an enzyme used in synthesis of Cholesterol - used to reduce high blood cholesterol levels (which = heart disease).
Aspirin irreversibly inhibits active site of COX enzymes, preventing synthesis of prostaglandins and thromboxane - chemicals responsible for producing pain and fever
Non - competitive inhibition
Inhibitors bind to the enzyme at a location other than the active site. This alternative site is called the ‘ allosteric site ‘.
The binding of this inhibitor leads the enzyme’s tertiary structure to change - meaning the active site changes.
This results in active site no longer having a complementary shape to the substrate therefore unable to bind and carry out its function.
It doesn’t compete therefore a ‘Non-Competitive Inhibitor’.
Effects on rates of reaction
Increasing concentration of Inhibitor - decreased rate of reaction as more active sites are unavailable
Examples of Non-competitive Inhibitors
Non-Competitive Inhibitors can be irreversible or reversible. Irreversible inhibitors usually very toxic.
Organophosphates used as insecticides and herbicides irreversibly inhibit the enzyme ‘acetyl cholinesterase’ - enzyme necessary for nerve impulse transmission. This leads to muscle cramps, paralysis or even death
Proton pump Inhibitors (PPI) are used to treat long term indigestion. They irreversibly block an enzyme system responsible for secreting H ions into the stomach - making them very effective in reducing excess production of acid (could lead to ulcers).
End product Inhibition
This is the term used for enzyme inhibition that occurs when the product of a reaction acts as an inhibitor to the enzyme that produces it. This serves as a ‘negative feedback’ control mechanism for the reaction. This means excess products aren’t made
Respiration = metabolic pathway resulting in production of ATP. Glucose is broken down in a number of steps.
2 phosphate groups added to the glucose molecule. The addition of the 2nd phosphate group (which results in the initial breakdown of the glucose molecule) is catalysed by the enzyme ‘phosphofructokinase’ (PFK).
When cells have a lot of ATP, ATP competitively inhibits PFK (ATP is competing against the actual substrate that PFK normally binds to the active site) and therefore less ATP production. So ATP regulates its own production.