Enzyme theory application

Leger C, Lederer F, Guigliarelli B, Bertrand P. Electron flow in multicenter enzymes theory, applications, and consequences on the natural design of redox chains. J Am Chem... 

Magnetic moment, 153, 155, 160 Magnetic quantum number, 153 Magnetization, 160 Magnetogyric ratio, 153, 160 Main reaction, 237 Marcus equation, 227, 238, 314 Marcus plot, slope of, 227, 354 Marcus theory, applicability of, 358 reactivity-selectivity principle and, 375 Mass, reduced, 189, 294 Mass action law, 11, 60, 125, 428 Mass balance relationships, 19, 21, 34, 60, 64, 67, 89, 103, 140, 147 Maximum velocity, enzyme-catalyzed, 103 Mean, harmonic, 370 Mechanism classification of. 8 definition of, 3 study of, 6, 115 Medium effects, 385, 418, 420 physical theories of, 405 Meisenheimer eomplex, 129 Menschutkin reaction, 404, 407, 422 Mesomerism, 323 Method of residuals, 73 Michaelis constant, 103 Michaelis—Menten equation, 103 Microscopic reversibility, 125... 

In the enzyme design approach, as discussed in the first part of this chapter, one attempts to utilize the mechanistic understanding of chemical reactions and enzyme structure to create a new catalyst. This approach represents a largely academic research field aiming at fundamental understanding of biocatalysis. Indeed, the invention of functional artificial enzymes can be considered to be the ultimate test for any theory on enzyme mechanisms. Most artificial enzymes, to date, do not fulfill the conditions of catalytic efficiency and price per unit necessary for industrial applications. 

C.J. Mcneil, D. Athey, M. Ball, W.O. Ho, S. Krause, R.D. Armstrong, J.D. Wright, and K. Rawson, Electrochemical sensors based on impedance measurement of enzyme-catalyzed polymer dissolution theory and applications. Anal. Chem. 67, 3928-3935 (1995). 

Several copper enzymes will be discussed in detail in subsequent sections of this chapter. Information about major classes of copper enzymes, most of which will not be discussed, is collected in Table 5.1 as adapted from Chapter 14 of reference 49. Table 1 of reference 4 describes additional copper proteins such as the blue copper electron transfer proteins stellacyanin, amicyanin, auracyanin, rusticyanin, and so on. Nitrite reductase contains both normal and blue copper enzymes and facilitates the important biological reaction NO) — NO. Solomon s Chemical Reviews article4 contains extensive information on ligand field theory in relation to ground-state electronic properties of copper complexes and the application of... 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

Tapia, O., Paulino, M. and Stamato, F. M. L. G. Computer assisted simulations and molecular graphics methods in molecular design. 1.Theory and applications to enzyme active-site directed drug design,... 

For the time being, our basic understanding of pressure effects is far from complete. However, some new developments concerning theory and application have occurred over the years. A short theoretical treatment of pressure effects was presented almost 30 years ago (Laidler, 1951). In this article we will present an extensive treatment of the present theoretical basis for pressure effects, incorporating contemporary knowledge of enzyme kinetics, physical biochemistry, and high-pressure theory. The theoretical level in this field is still not very sophisticated, but it is important enough so that theoretical considerations should be applied when future experiments are planned. 

Easterby proposed a generalized theory of the transition time for sequential enzyme reactions where the steady-state production of product is preceded by a lag period or transition time during which the intermediates of the sequence are accumulating. He found that if a steady state is eventually reached, the magnitude of this lag may be calculated, even when the differentiation equations describing the process have no analytical solution. The calculation may be made for simple systems in which the enzymes obey Michaehs-Menten kinetics or for more complex pathways in which intermediates act as modifiers of the enzymes. The transition time associated with each intermediate in the sequence is given by the ratio of the appropriate steady-state intermediate concentration to the steady-state flux. The theory is also applicable to the transition between steady states produced by flux changes. Apphcation of the theory to coupled enzyme assays makes it possible to define the minimum requirements for successful operation of a coupled assay. The theory can be extended to deal with sequences in which the enzyme concentration exceeds substrate concentration. 

After a long initial period of about a hundred years, with mysterious theories and several technical applications, where one (diastase) even achieved economic importance, research on enzymes obtained a chemically scientific status. 

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. 

Alberty, R. A., and Hammes, G. G. (1958). Application of the theory of diffusion-con-trolled reactions to enzyme kinetics. J. Phys. Chem. 62, 154-159. 

Jaenicke, R. (1987). Folding and association of proteins. Prog. Biophys. Mol. Biol. 49,117-237. Koshland, D.E. (1958). Application of a theory of enzyme specificity to protein synthesis. Proc. Natl. Acad. Sci. USA 44, 98-104. 

The key equation resulting from the application of two known theories, the Bom-Haber cycle and the transition-state theory, was formulated for any catalyst and without reference to enzymes (Kurz, 1963) a good derivation can be found in the article by Kraut (1988). 

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