Enzymatic Catalysis—Lessons from Biochemistry

To really understand the basics of catalysis, we can try to understand how some of the best catalysts work. Enzymes are biochemical catalysts with exceptional abilities to speed up reactions. There are enzymes in your body that are highly selective and work in water and at mild temperatures, and some are so fast that they can produce their products as fast as the reactants can diffuse to them. 

Molecules have to colUde to react. Most reactions are run in solution, so as a solution gets more concentrated, collisions increase and so does the rate. But there is an upper limit, often determined by solubility, on how concentrated the solution can get. A concentration landmark is that pure water is 55.5 mol/liter pure benzene, QH, is 11.1 mol/liter. Often chemists must run reactions at 1 mol/liter or less. In addition, not all collisions are effective because usually certain parts of the reactant molecules must hit to react otherwise they just bounce off each other. This orientation requirement is part of the AS portion of the barrier, AG = iStfi — TAS. If the reactive partners are part of the same molecule (intramolecular reactions), they collide as the molecule twists and turns much more frequently than if they were separate. In fact, intramolecular reactions can get effective concentrations of well over a milhon mol/liter  

It is believed that proximity and orientation are critical to the way enzymes accelerate reactions. The key is to increase the number of effective collisions between reactive partners. Not only are the reactive partners undergoing a huge number of collisions within the active site of the enzyme, but the active site is also orienting them correctly. The slow step for some enzymes is just getting the reactants into the active site, the diffusion-controlled limit. 

An enzyme active site often has a unique shape only molecules that have the right shape will fit. This allows the enzyme to select for the correct reactants among all those swimming in the cell soup. Even better, the correct reactant usually has to fit in the active site in the proper orientation to react. This first step takes care of theA5 component of the A G barrier by binding the reactant in the proper orientation for reaction. What is left of the barrier is the Afff component, which can be lowered by stabilization of the transition state(s) or intermediate(s). 

The enzyme active site can also twist the reactant into a more reactive conformation, and can provide the perfect microenvironment for reaction proper solvation, nearby acid or base catalysts, needed electrophiles and nucleophiles. 

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Section 2.8 Enzymatic Catalysis - Lessons from Biochemistry... 

Narlikar GJ and Daniel Herschlag D (1997) Mechanistic aspects of enzymatic catalysis Lessons from comparison of RNA and protein enzymes. Annual Reviews in Biochemistry 66 19-59. 

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