Structural Biochemistry/Enzyme Catalytic Mechanism/Catalysis
Introduction[edit | edit source]
The process of catalysis increases the rate of a chemical reaction with the use of a catalyst. A catalyst lowers the activation energy of a reaction, which allows for a different reaction pathway to be followed. This new pathway requires less energy, which as a result, increases the rate of the reaction. A catalyst does not affect the equilibrium of the overall reaction, or make the reaction more favorable by any means. It simply serves to speed up the reaction rate, often exponentially. During the reaction, the catalyst is not consumed and thus the same enzyme may be used to catalyze the same reaction again in the future. This is the reason why catalysts generally affect the kinetic state of a substrate converting into a product, but is not mentioned in terms of thermodynamics of an overall reaction as it plays no role in affecting change in energy. An enzyme lowers the activation energy of a reaction by easing the formation of the transition state between the reactants and the products. When an enzyme binds to its proper substrate, it releases binding energy; that is, the free energy released in forming many weak bonds (hydrophobic, H-bonds, electrostatic interactions). Only an enzyme's intended substrate can release the maximum binding energy, explaining why enzymes demonstrate such a high level of specificity. The substrate in the enzyme-substrate complex must reach its transition state, though, for the most binding energy to released. Once the transition state has been achieved and the binding energy released, its high instability requires it to shift either to the side of the reactants or to the side of products--with more transition-state substrate shifting to whichever state is more thermodynamically favorable. In other words, the equilibrium of a catalyzed reaction depends solely on the free energy of the reacting substrate relative to that of the products: delta-G.
Covalent Catalysis[edit | edit source]
In Covalent Catalysis, the substrate forms a temporary covalent bond with a reactive group, usually a good nucleophile, in the active site, and the complex is then incorporated into the catalysis of the reaction. The covalent complex is more reactive than the substrate itself originally was. This may serve to reduce the energy required for later states of the reaction. The enzyme, of course, is not used up during the reaction and thus must be regenerated at some point by breaking the temporary covalent bond. An example of an enzyme following such a mechanism is chymotrypsin, which is an enzyme that cleaves peptide bonds by a hydrolysis reaction, or a protease. Some examples of good nucleophilic groups in proteins are serine and tyrosine (presence of a hydroxyl group), histidine (imidazole group), lysine (amino group), cystine (thiol group), and aspartate and glutamate (carboxylate group).
Acid-Base Catalysis[edit | edit source]
In Acid-Base Catalysis, an acid or base catalyzes a reaction by being a proton donor or acceptor. The acid is often a donor whereas the base is often an acceptor (e.g. a hydroxyl ion). This is often seen in organic chemistry, when a catalyst donates a proton to a hydroxyl group to create water, a very good leaving group compared to the hydroxyl, which is a poor leaving group. This idea applies for other reactions in organic chemistry as well, even if water is not involved - the catalyst donates or accepts a proton to create a better leaving group in order to jump start the reaction. Again, the catalyst is ultimately formed again at some point in the reaction and is not consumed.
In specific acid-base catalysis, water serves as the catalyst. The hydronium ion (H3O+) serves as the proton donor while the hydroxide ion (OH-) serves as the proton acceptor.
In general acid-base catalysis, molecules other than water take the role of the catalyst. Examples may be cofactors, or residues of protons from amino acid side chains. Histidine, for example, is an effective catalyst since its pKa is very close to physiological pH.
Catalysis by Approximation[edit | edit source]
Catalysis By Approximation is described by two substrates bound to one another so that they are close together near the site of reaction along the enzyme, thus increasing the reaction rate. A substrate may also be brought into contact with a catalytic group rather than with another substrate. The orientation of the two molecules involved here are important to the process.
Metal Ion Catalysis[edit | edit source]
In Metal Ion Catalysis, metal ions function as the catalyst, hence the name. Metal ions may bind to substrates to enhance their interaction with an enzyme by ensuring a proper orientation. The metal ion acts as a bridge between the substrate and the enzyme increasing the binding energy. Alternatively, the metal ion may bridge the substrate to a nucleophilic group. The metal ion may stabilize negative charges on a leaving group to make it a better leaving group, or shield negative charges on the molecule to allow for nucleophilic attack which otherwise may have been repelled. It may also participate in oxidation-reduction reactions by changing their oxidation state.