Enzymes Study Materials

Enzymes/Drug Targets Learning Objectives 1. Describe enzymes as specialised proteins that catalyse biochemical reactions (catalytic mechanism of chymotrypsin) 2. Explain the kinetics of enzyme reactions and the modes of enzyme inhibition, both reversible and irreversible 3. Describe the chemical interactions between Drug (substrate) and Enzyme 1. Structure and function of enzymes Notes • • • Globular proteins acting as the body’s catalysts. Made up of a series of amino acids, they can vary in size, primary, secondary, tertiary, quaternary. - Without them the body processes would be very slow Speed up time for reaction to reach equilibrium Lower the activation energy of a reaction - Enzymes would do some sort of biochemical change to a substrate molecule or a start up molecule, it needs to modify it somewhere to make it useable by the body. - They body cannot reach 100, because we will die, so we need an enzyme to speed things up. LDH is the enzyme LDH can be both an oxidising agent or reducing agent, depending on what direction it is going. Lowering the activation energy of reaction • • Transition site: the most active site, the highest level of activation energy required by an enzyme to convert a molecule into a product. - It does not last very long - It is quite unstable at this stage - Gibbs energy does not change in an enzyme reaction The pink curve: activation energy lowered Note • Enzymes lower the activation energy of a reaction, but DG remains the same The Active Site • Methods of enzyme catalysis • • • • • • • • • Provides a reaction surface (the active site): this is the region where the substrate can bind to the enzyme, to site for the moment and perform its biochemical reaction. - The rest of the protein it is just there designed but it does not perform any particular function, actually modifying the substrate. Provides a suitable environment (hydrophobic) - Proteins and amino acids are highly water soluble Brings reactants together Positions reactants correctly for reaction - It needs to choose a particular site, it cannot be anywhere random Weakens bonds in the reactants - Bonds need to break so that the final product can be created Provides acid / base catalysis - Weak acids and weak bases Provides nucleophilic groups - Hydroxyl groups, amino groups etc. These have a high density of electrons are willing to donate those electrons to an electrophilic part of the molecule Stabilises the transition state with intermolecular bonds Proteins made up of a series amino acid, they will be prone to degradation or performance, based on their pH. There are acidic, basic and neutral pH. - pH may modify the enzyme of degrade the enzyme • • - Pepsin needs a very acidic pH. There are different classes of enzymes Nucleophiles The Active Site • • • • Hydrophobic hollow or cleft on the enzyme surface Accepts reactants (substrates and cofactors e.g. B12, B6 magnesium, zinc) Contains amino acids which - bind reactants (substrates and cofactors) - participate in the enzyme-catalysed reaction Amino acids get linked up from one amino acid to the other: they can form ultra-helixes like curling up. - They can also form beta sheets Substrate Binding 1. Induced fit • • • • As soon as the substrate gets in close proximated to the active site it causes induced fit. - This means it re-orientates itself in such way that will come and make it comfortable for the substrate to come and bind and expose all of the required bonding that is required for the substrate to come and sit. Active site is nearly the correct shape for the substrate Binding alters the shape of the enzyme (induced fit) The binding process can strain bonds in the substrate: because it has never been bonding before, so after bonding it may weaken some bonds because we want to make some so after binding it will weaken some bonds, biochemical change it, such as • hydrolysing it or break up the amide bonds, so to do this we need to weaken some bonds, so it causes some sort of strain. Binding involves intermolecular bonds between functional groups in the substrate and functional groups in the active site Bonding forces • Ionic (partial charge) - There will be much of a force. - There will NOT be covalent bonding, because this is really strong so it will be really hard to break. - There needs to be weak bonding, because we don’t want something to come and bind to the enzyme and at the same time permanently stick. This is because the process needs to be revisable. It needs to do its’ change, come here, bind, done your chemical reaction and get out, change it to the new product and the leave, so that the enzyme can act on the second substrate.