Principles of Enzyme Catalysis

What is a catalyst According to textbooks on physical chemistry, a catalyst is a substance that encourages chemical transformations in other substances without itself being affected. This means that after each act of substrate transformation into a product the catalyst must return to its initial state. The initial and final states of an enzyme molecule do not alter, while the concentrations of substrate and product molecules ( 4, or Bj in (2.1)) will change with the enzyme turnover. 

Before going further in our analysis of the principles of enzyme action, we must say a few words about a widely held opinion among biochemists. Many of them think that there exists a general theory of catalysis in chemistry, and we need only to apply this theory to the more complex enzyme reactions. We think that this opinion is misleading. There is no such thing as a more-or-less self-consistent general theory of catalysis. 

It is rather doubtful, however, if enzyme catalysis can be considered as a kind of homogeneous catalysis. In this case, the catalyst is not just another low-molecular reactant, but a huge protein molecule with a defined surface that plays an essential role in the catalytic process. For this reason, many scientists relate enzyme catalysis to heterogeneous catalysis. 

If we look at the experimental and theoretical aspects of heterogeneous catalysis, we will see that the state of affairs here is even worse than in enzyme catalysis. This is mainly due to the fact that it is easier to perform a reproducible experiment with purified enzymes than in the case of many solid catalysts. To be sure, enzymes are complicated substances, and it is necessary to be extremely careful during their preparatory isolation. However, being synthesized within the cell of a matrix, enzyme molecules represent practically identical copies. Therefore, the reproducibility of their functioning is, as a rule, much better than that of the solid catalysts of abiogenic origin. The identity of enzyme molecules is limited, however, by the possibility of the existence of plural forms of the enzymes, that are determined, in turn, by the chemical composition and the primary chemical structure (the sequence of amino acids residues in the polypeptide chain) of a protein molecule. Most proteins are sufficiently complex, and thus can exist in several conformational modifications. 

The notion of enzyme activity requires certain elucidation. What is the meaning of the statements A chemical reaction is accelerated by the enzyme. With what should we compare the rate of enzyme reaction Is this the rate of the same reaction running without the enzyme As a matter of fact, the same reaction may be impossible without the enzyme. For most enzyme processes, there is a sequence of several reactions with several stable and unstable intermediates. Hence, it is not always possible to realize the same path of the overall reaction without the enzyme. Kosower introduced the concept of a so-called congruent model system, i.e., a chemical system in which the same overall reaction with the same stable intermediates is actualized [1]. The reaction path between stable intermediates can of course be essentially different. We should therefore compare the rate of the enzyme reaction with the rate of a chemical transformation of a corresponding congruent system. 

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Proton transfers are particularly common. This acid-base catalysis by enzymes is much more effective than the exchange of protons between acids and bases in solution. In many cases, chemical groups are temporarily bound covalently to the amino acid residues of the enzyme or to coenzymes during the catalytic cycle. This effect is referred to as covalent catalysis (see the transaminases, for example p. 178). The principles of enzyme catalysis sketched out here are discussed in greater detail on p. 100 using the example of lactate dehydrogenase. 

The principles of enzyme catalysis discussed on p. 90 can be illustrated using the reaction mechanism of lactate dehydrogenase (LDH) as an example. 

Chorismate Mutase Analysing Fundamental Principles of Enzyme Catalysis... 

Apart from technical considerations, it is important to identify what mechanistic questions can be addressed by the calculations. For example, different possible candidates for an active site base could be compared, or perhaps the stability of various proposed intermediates could be studied. There is a wealth of unanswered questions regarding aspects of specific enzyme reaction mechanisms, and also on the general principles of enzyme catalysis (e.g. what factors or interactions are most important in reducing the activation energy, how the enzyme reaction compares to the equivalent reaction in solution, etc.). Different types of calculation, within the QM/MM framework, may be required to address different types of question, as demonstrated by the variety of applications and approaches described in section 6. Consider what... 

Before specific examples are discussed, we want to briefly recall the fundamental principles of enzyme catalysis. The astonishing efficiency of protein-based catalysts is the result of precisely positioned functional groups, which constitute a dynamic binding pocket for the substrate(s) and the transition state of the reaction. For a unimolecular reaction (S P), the simplified energy profile is depicted in Fig. 1. 

Constructing bio.sensors with greater reliability requires a better understanding of the basic principles of enzyme catalysis and immunochemical reactions, protein structures, pathways for receptor-based signal amplification, and the interfacial behavior of biocompounds at the artificial transducer surface. Biosen.sor research must therefore be directed toward the following points ... 

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