Bioorganic chemistry and enzyme reactions

Finally, enzymes have the special ability of stabilizing the transition state of the reaction. There are multiple ways for this mechanism to operate, depending on the nature of electronic density accumulation and dissipation in the activated complex. It is important to note that this approach, albeit powerful, has its limitations for multistep reactions where several transition states are encountered on route from the substrate to the product. 

Lowering the barrier for the rate-limiting step will only accelerate the reaction to a point where the other elementary step becomes rate limiting. In this situation, the enzyme must confront the problan by finding a path that lowers the barrier to each of the elanentary steps. Evolutionary pressure can lead to an enzyme-catalyzed reaction where all of the barriers are similar in height and no one step is rate limiting. 

In the above situation, a perfect enzyme should function by organizing all kinetically important species, including the substrate and the possible intermediates, in a stereoelectronically favorable conformation. This scenario would require a conformationally flexible enzyme active site with the multiplicity of conformational states, each suited for a different intermediate/tiansition state combination. 

The mechanistic studies of enzyme catalysis constitute a very large field where rapid progress has been fueled by the recent advances in X-ray crystallography techniques and new spectroscopic methods. We will restrict ourselves to a small number of illustrative examples and refer the reader to an earher thorough discussion of stereoelectronic effects in biomolecules by Gorenstein.  

The mechanistic work on the hydrolysis of acetals provides a stereoelectronic rationale for the earlier suggestions that this essential conformational change shonld be involved in the enzyme-catalyzed p-glycosyl transfer reactions either as a part of the initial binding process or in one of the subsequent isomerization steps. The lone pair-a overlap gradually increases as the ring flattens into the half-chair conformation and an alternative mode of stereoelectronic assistance becomes possible. 

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