Enzyme inhibitors

Enzyme inhibitors

1. 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 affects the enzyme's turnover number ->some may block the active site & some change the shape of the active site ->both of these will inhibit the formation of ES complexes & therefore of product formation.

2. Competitive inhibitors

   • ~competitive inhibitors are substances whose molecules have a similar shape to an enzyme's substrate molecules
     • *the competitive inhibitor fits into the active site & so a substrate molecule cannot enter
     • *the amount of inhibition depends on the relative conc of substrate & inhibitor moles ->more inhibitors molecules means more inhibitors will collide with active sites & so the effect of inhibition is greater
     • *incr substrate conc effectively 'dilutes' the effect of the inhibitor ->if enough substrate is added =inhibitor is unlikely to collide with the enzyme
       • *they compete directly with substrate moles for a position on the enzyme's active site ->forming an enzyme- inhibitor complex that is catalytically inactive
         • *once on active site, inhibitor isn't changed by enzyme, as the normal substrate molecule would be
           • *the presence of the inhibitor prevents the substrate molecule from joining to the active site ->reduces the rate of formation of ES complexes & of product mole formation
             • *a competitive inhibitor reduces the number of free enzyme active sites available for the substrate moles to bind to & form ES complexes
               • *most enzyme inhibition by competitive inhibitors is reversible ->as collisions between enzyme & substrate or inhibitor moles are random-> incr the conc of substrate would reduce the effect of reversible competitive inhibitions, as there would be more chance of an enzyme mole colliding with a substrate mole that with an inhibitor mole
                 • *if the competitive inhibitor binds irreversibly to the enzyme's active site =inactivator

3. Non- competitive inhibition

   • ~if the inhibitor mole binds to the enzyme somewhere other than at the active site, it's called non- enzyme inhibition
     • *non- competitive inhibitors don't compete with substrate molecules for a place on an enzyme's active site ->they attach to enzyme molecule in a region away from the active site (allosteric) ->in doing so they disrupt the enzyme's tertiary structure & change its shape
     • *this distortion changes the shape of the active site so that it's no longer complementary to the shape of the substrate molecule, & the substrate molecule can no longer bind to the enzyme's active site = ES complexses cannot form
     • *max rate of reaction is reduced by presence of non- competitive inhibitors, ->adding more substrate might allow the reaction to attain the new, lower rate ->but even very high conc of substrate won't allow rate of reaction to return to its uninhibited max
     • *more inhibitor moles are present the greater the degree of inhibition ->as more enzyme moles are distorted & either cannot form ES complexes or cannot complete the catalytic reaction involving Es complexes
     • *some non-competitive inhibitors bind reversibly to allosteric site ->other non- competitive inhibitors bind irreversibly to allosteric site

4. End- product inhibition

   • ~one way in which enzyme- catalysed reactions may be regulated is by end- product inhibition ->after the catalysed reaction has reached completion, product moles may stay tightly bound to the enzyme ->in this way, the enzyme cannot form more product than cell needs = negative feedback

5. Control of metabolic sequences

   • ~many metabolic processes, such as photsynthesis & respiration, involve a series of enzyme -catalysed reactions
     • *product of one enzyme- catalysed reaction becomes the substrate for the next enzyme catalysed reaction in the metabolic pathway
       • *cells don't need to accumulate too much of the end product, so the product of the last enzyme catalysed reaction in the metabolic pathways may attach to a part of the first enzyme in the pathway, but not as its active site
         • *this binding changes shape of enzyme 1's active site, preventing the pathway from running ->this is non- competitive inhibition, but it's reversible
           • *when the conc of this product within the cell falls, those moles will detach from enzyme 1 & allow its active site to resume its normal shape: the metabolic pathway can run again.
   • ~multi- enzyme complexes incr the efficiency of metabolic reactions without incr substrate conc ->as they keep the enzyme & substrate moles in the same vicinity & reduce diffusion time
     • ~many metabolic reactions are carried out in particular regions or organelles in cells, & this also incr efficiency of metabolism ->some of enzymes within organelles are bound into the organelle membrane