Enzymes & Regulation of Enzymes Catalysts speed up reactions by lowering the activation energy associated with reactions. In the following exergonic reaction, the overall free energy change of the reaction with the catalyst is unchanged but the energy of activation(E A ) is greatly reduced. – products have less energy than reactants – enzymes are not used in the reactions but free to couple with new reactants – What is the coupled metabolic reaction?

Biological Enzymes Biological enzyme are specific for the substrate (reactant) that they couple with. – substrates bind to the enzyme's active site(groove or fold) the conformation (3D shape) of the enzyme and reactant must be an exact fit (lock & key) – the reaction takes place while bound – The product is released once the reaction is completed

Mechanisms of Enzyme Interactions Binding orients molecules so that their active sites (pocket or groove) are in the correct position for the reaction to take place – Once bound the enzyme may undergo a slight conformation change to make the fit more snug… called an induced fit – Reaction is fast with typical enzymes operating at around 1000rxns/sec – Enzymes may also catalyze the reverse rxn in order to maintain equilibrium

Mechanisms of Enzyme Interactions 1 st … maintains proper substrate orientation for bonding 2 nd … The enzyme may stretch or bend bonds in the substrate weakening them for bonds that must be broken 3 rd … It may create a micro environment different than in the cytosol with acidic side chains 4 th … the enzyme may actively participate forming brief covalent bonds with the substrate in order to complete the reaction and return side chains to original state

Enzyme Regulation Most enzymes require activation (cofactors & coenzymes) and regulation (inhibitors) in order to operate properly in the body. – Vitamins are common cofactors for metabolic pathways – Most enzyme catalyzed reactions require activation and regulation to properly function Without regulation all the metabolic pathways would operates simultaneously leading to chaos. Regulation strategies include: Inhibitors inactivate enzymes until needed – Competitive inhibition … inhibitor weekly binds to the active site – Non-competitive inhibitor binds to another site to change the conformation of the active site » Many metabolic toxins work in this fashion

Allosteric Regulation allosteric regulation - the change of conformation of the active site due to the binding of a molecule at another site most allosterically active enzymes are made of 2 or more subunits with 2 or more active sites – allosteric activator - stabilizes the active site to better fit the substrate – allosteric inhibitor - changes the active site so that it doesn't fit the substrate – allosteric cooperativity -the binding of the substrates activates additional active sites on the enzyme

Feedback Inhibition – the product binds to an enzyme to inactivate it once it is abundant in the cytosol – used in multiple step processes to inhibit further formation of product