Enzyme theory problems

Clearly, proximity and orientation play a role in enzyme catalysis, but there is a problem with each of the above comparisons. In both cases, it is impossible to separate true proximity and orientation effects from the effects of entropy loss when molecules are brought together (described the Section 16.4). The actual rate accelerations afforded by proximity and orientation effects in Figures 16.14 and 16.15, respectively, are much smaller than the values given in these figures. Simple theories based on probability and nearest-neighbor models, for example, predict that proximity effects may actually provide rate increases of only 5- to 10-fold. For any real case of enzymatic catalysis, it is nonetheless important to remember that proximity and orientation effects are significant. 

In terms of the carbanion equivalent, the enolase superfamily has a strong relation with decarboxylation reaction. This family is characteristic in its promiscuity. If one is reminded of the phrase lock and key theory for the relation between the substrate and the enzyme, the word promiscuity of the enzyme may be unbelievable. However, in addition to natural promiscuity, we can change the enzyme to be promiscuous by introducing mutation, especially in the case of the enolase superfamily. This will be one of the challenging problems in future. For that purpose, biotechnology and informatics skill will be essential tool in addition to precise analysis of the reaction mechanism. 

Quantum mechanics is essential for studying enzymatic processes [1-3]. Depending on the specific problem of interest, there are different requirements on the level of theory used and the scale of treatment involved. This ranges from the simplest cluster representation of the active site, modeled by the most accurate quantum chemical methods, to a hybrid description of the biomacromolecular catalyst by quantum mechanics and molecular mechanics (QM/MM) [1], to the full treatment of the entire enzyme-solvent system by a fully quantum-mechanical force field [4-8], In addition, the time-evolution of the macromolecular system can be modeled purely by classical mechanics in molecular dynamicssimulations, whereas the explicit incorporation... 

A hypercycle is a more complex organisation form. Its precondition is the presence of several RNA quasi-species which are able to amalgamate chemically with certain proteins (enzymes or their precursors). If such a protein is linked to a quasi-species, the resulting duo favours the replication of a second quasispecies. According to Dyson, the linked populations get stuck in a stable equilibrium. Problems occur at this level Any theory on the origin of replication has the central problem that the replication process must occur perfectly in order to ensure survival . If there are replication errors, these will increase from generation to generation, until the system collapses the error catastrophe has then occurred ... 

Such considerations raise the concept of the intrinsic kinetic isotope effect—the effect of isotopic substitution on a specific step in an enzyme-catalyzed reaction. The magnitude of an intrinsic isotope effect may not equal the magnitude of an isotope effect on collective rate parameters such as Vmax or Emax/ m, unless the isotopi-cally sensitive step is the rate-limiting or rate-contributing step. To tackle this problem, Northrop extended the kinetic theory for primary isotope effects in enzyme-catalyzed reactions. His approach can be illustrated with the following example of a one-substrate/two-intermedi-ate enzyme-catalyzed reaction ... 

Here the problem of formulating a reaction rate expression is much more difficult because there are many atoms involved, and consequently the statistical mechanics and quantum mechanics are much more complex. We wiU consider the forms of rate expressions for surface- and enzyme-catalyzed processes in Chapter 7, but fundamental theories are usually not obtainable. 

The second aspect refers to the protein nature of enzymes. In 1894 Fischer (Fischer, 1909) stated that amongst the agents which serve the living cell the proteins are the most important. He was convinced that enzymes are proteins. The role of this key problem may be illustrated with a citation from Fruton (1979) ... the peptide theory was indeed only a hypothesis fifty years after Franz Hofmeister and Emil Fischer advanced it... (in 1902). The nature and stracture of proteins remained unknown throughout the 19th century remarkably, technological applications were nevertheless put into practice since the middle of the century (see above), based on their action, eventually recognized as catalysis, only. 

Investigations with the graphs of non-linear mechanisms had been stimulated by an actual problem of chemical kinetics to examine a complex dynamic behaviour. This problem was formulated as follows for what mechanisms or, for a given mechanism, in what region of the parameters can a multiplicity of steady-states and self-oscillations of the reaction rates be observed Neither of the above formalisms (of both enzyme kinetics and the steady-state reaction theory) could answer this question. Hence it was necessary to construct a mainly new formalism using bipartite graphs. It was this formalism that was elaborated in the 1970s. 

Enzymes have improved over the years so that food stains on clothes, and unmentionable stains on undergarments, now present no problem. In the late 1980s, enzymes were engineered that could resist the action of the peroxide bleach and by 2000 it was possible to have a mix of all kinds of enzymes in the same detergent. Because enzymes are themselves protein molecules, a protease enzyme could in theory attack other enzymes and digest them as well, so special varieties have been developed to overcome this. Today, enzyme demand is... 

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