2.4.8 Enzyme inhibitors

2.4.8 Enzyme inhibitors

1. Inhibitors

   • Inhibitors are substances that reduce the activity of an enzyme
     • They do this by combining with the enzyme molecule in a way that influences how the substrate binds to the enzyme or the turnover number
     • Some may block the active site and some may change the shape of the active site
       • Both of these will inhibit the formation of enzyme substrate complexes and product formation

2. Competitive inhibitors

   • Competitive inhibitors are substances whose molecules have a similar shape to an enzymes substrate molecule
   • The competitive inhibitor fits into the active site so a substrate molecule cant enter
   • The amt. of inhibition depends on the relative conc. of substrate and inhibitors molecules. More inhibitor molecules means more inhibitors collide with active sites so the effect is greater
   • Increasing substrate conc. effectively 'dilutes' the inhibitor effects. If enough substrate is added, the inhibitor is unlikely to collide with the enzyme
   • Inhibitors compete with the substrate molecules for a position on the active site, forming an enzyme-inhibitor complex that is catalytically inactive
   • Once on the active site, the inhibitor is not changed by the enzyme
   • The presence of the inhibitor prevents the substrate molecules joining to the active sire which reduces the formation of the ES complex and product molecule complex
   • A competitive inhibitor reduces the number of free enzyme active sites available for substrate molecules to bind to and form ES complexes
   • Most enzyme inhibitor by competitive inhibitors is reversible as collisions between enzyme and substrate or inhibitors are random, increasing the conc of substrate would reduce the effect of reversible competitive inhibition as there is more chance of an enzyme colliding with a substrate than inhibitor
   • If the competitive inhibitor binds irreversibly to the active sire, it is called an inactivator

3. Non-competitive inhibition

   • If the inhibitor binds to the enzyme somewhere other than the active site, it is non-competitive inhibition
   • Non-competitive inhibitors dont compete with substrate molecules for a place on the active site. They attach to the enzyme molecule in a region called the allosteric site, away from the active site. In doing so, they disrupt the enzymes tertiary structure and change its shape
   • This distortion changes the active sites shape so it is no longer complementary to the substrate molecule meaning the substrate can no longer bind to the active site and form an ES complex
   • The max. rate of reaction is reduced by the presence of non-competitive inhibitors. Adding more substrate might allow the reaction to attain the new lower rare but won't allow the rate of reaction to return to its inhibited maximum
   • The more inhibitor molecules present, the greater the degree if inhibition as more enzyme molecules are distorted and can't form ES complexes or cant complete the catalytic reaction
   • Some non-competitive inhibitors bind reversible to the allosteric site. Others bind irreversibly

4. End-product inhibition

   • One way enzyme-catalysed reactions may be regulated is by end-product inhibition
   • After the catalysed reaction has reached completion, product molecules may stay tightly bound to the enzyme
   • This way, the enzyme cant form more of the product than the cell needs. This regulation is an example of negative feedback

5. Control of metabolic sequences

   • Many metabolic processes, like photosynthesis and respiration, involve a series of enzyme-catalysed reactions
   • The product of one enzyme-catalysed reaction becomes the substrate for the next catalysed reaction in the metabolic pathway
   • Cells don't need to accumulate too much of end-product so the product of the last catalysed reaction may attach to part of the first enzyme in the pathway but not its active site
   • This binding changes the shape of enzyme 1's active site, preventing the pathway from running. This is non-competitive inhibition but its reversible
   • When the conc. of the product within the cell falls molecules will detach from enzyme 1 allowing its active site to return to. normal shape and the metabolic pathway runs again
   • An example is shown in the figure. The substrate A is converted into product B by enzyme 1. Product B is the substrate for enzyme 2, converted to product C and so on. The end product E can bind to enzyme 1 and act as a non-competitive inhibitor meaning product E won't build up in the cell because as E is made it slows the formation by inhibiting the first enzyme in the sequence
   • Multi-enzmye complexes increase the efficiency of metabolic reactions without increasing substrate conc, as they keep the enzyme and substrate molecules in the same vicinity and reduce diffusion time

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