Of enzymic reactions

Aqvist, J., Warshel, A. Simulation of enzyme reactions using valence bond force fields and other hybrid quantum/classical approaches. Chem. Rev. 93... 

E is the field due to the solute charges alone. The Langevin dipole method has been wide used by Warshel in his studies of enzyme reactions (see Section 11.13.3). 

Aqvist J and A Warshel 1993. Simulation of Enzyme Reactions Using Valence Bond Force Fields a Other Hybrid Quantum/Classical Approaches. Chemical Reviews 93 2523-2544. 

Chelation is a feature of much research on the development and mechanism of action of catalysts. For example, enzyme chemistry is aided by the study of reactions of simpler chelates that are models of enzyme reactions. Certain enzymes, coenzymes, and vitamins possess chelate stmctures that must be involved in the mechanism of their action. The activation of many enzymes by metal ions most likely involves chelation, probably bridging the enzyme and substrate through the metal atom. Enzyme inhibition may often result from the formation by the inhibitor of a chelate with a greater stabiUty constant than that of the substrate or the enzyme for a necessary metal ion. 

The QM-MM study of TIM was the first illustration of the potential of these methods for studying enzyme catalysis and has served as a reference for the protocol needed for subsequent studies of enzyme reactions. 

This study is particularly noteworthy in the evolution of QM-MM studies of enzyme reactions in that a number of technical features have enhanced the accuracy of the technique. First, the authors explicitly optimized the semiempirical parameters for this specific reaction based on extensive studies of model reactions. This approach had also been used with considerable success in QM-MM simultation of the proton transfer between methanol and imidazole in solution. 

A free energy study of malate dehydrogenase [29] using semiempirical QM-MM methods has also been reported, and that shidy also attributes many of the benefits to simulation of enzyme reactions found in the BPTP shidy. 

Enzymes are proteins of high molecular weight and possess exceptionally high catalytic properties. These are important to plant and animal life processes. An enzyme, E, is a protein or protein-like substance with catalytic properties. A substrate, S, is the substance that is chemically transformed at an accelerated rate because of the action of the enzyme on it. Most enzymes are normally named in terms of the reactions they catalyze. In practice, a suffice -ase is added to the substrate on which die enzyme acts. Eor example, die enzyme dial catalyzes die decomposition of urea is urease, the enzyme dial acts on uric acid is uricase, and die enzyme present in die micro-organism dial converts glucose to gluconolactone is glucose oxidase. The diree major types of enzyme reaction are ... 

This chapter solely reviews tlie kinetics of enzyme reactions, modeling, and simulation of biochemical reactions and scale-up of bioreactors. More comprehensive treatments of biochemical reactions, modeling, and simulation are provided by Bailey and Ollis [2], Bungay [3], Sinclair and Kristiansen [4], Volesky and Votruba [5], and Ingham et al. [6]. 

The catalytic action is specific and may be affected by the presence of other substances both as inhibitors and as coenzymes. Most enzymes are named in terms of the reactions they catalyze (see Chapter 1). There are three major types of enzyme reactions, namely ... 

In Chapter 16, we explore in greater detail the factors that contribute to the remarkable catalytic power of enzymes and examine specific examples of enzyme reaction mechanisms. Here we focus on another essential feature of enzymes the regulation of their aetimty. 

Theoretical Studies of Enzymic Reactions Dielectric, Electrostatic and Steric Stabilizations of the Carbonium Ion in the Reaction of Lysozyme A. Warshel and M. Levitt Journal of Molecular Biology 103 (1976) 227-249... 

Each of the processes shown in Figure 2.8 can be described by a Michaelis-Menten type of biochemical reaction, a standard generalized mathematical equation describing the interaction of a substrate with an enzyme. Michaelis and Men ten realized in 1913 that the kinetics of enzyme reactions differed from the kinetics of conventional... 

Despite the large size of an enzyme molecule, there is reason to believe that there are only one or a few spots on its surface at which reaction can occur. These are usually referred to as active centers. The evidence for this view of enzyme reactions comes from many kinds of observations. One of these is that we can often stop or slow down enzyme reactions by adding only a small amount of a false substrate. A false substrate is a molecule that is so similar to the real substrate that it can attach itself to the active center, but sufficiently different that no reaction and consequently no release occurs. Thus, the active center is blocked by the false substrate. 

The specificity of enzyme reactions can be altered by varying the solvent system. For example, the addition of water-miscible organic co-solvents may improve the selectivity of hydrolase enzymes. Medium engineering is also important for synthetic reactions performed in pure organic solvents. In such cases, the selectivity of the reaction may depend on the organic solvent used. In non-aqueous solvents, hydrolytic enzymes catalyse the reverse reaction, ie the synthesis of esters and amides. The problem here is the low activity (catalytic power) of many hydrolases in organic solvents, and the unpredictable effects of the amount of water and type of solvent on the rate and selectivity. 

The kinetics of enzyme reactions were first studied by the German chemists Leonor Michaelis and Maud Menten in the early part of the twentieth century. They found that, when the concentration of substrate is low, the rate of an enzyme-catalyzed reaction increases with the concentration of the substrate, as shown in the plot in Fig. 13.41. However, when the concentration of substrate is high, the reaction rate depends only on the concentration of the enzyme. In the Michaelis-Menten mechanism of enzyme reaction, the enzyme, E, and substrate, S, reach a rapid preequilibrium with the bound enzyme-substrate complex, ES ... 

Note. In Enzyme Nomenclature [23] dehydro names are used in the context of enzymic reactions. The substrate is regarded as the parent compound, but the name of the product is chosen according to the priority given in 2-Carb-2.2. 

Non-linearity during progession of enzyme reaction or an initial lag phase which is undetected and may result in significant error. 

The fluidity of blood is a result of the inhibition of a complex series of enzymic reactions in the coagulation cascade (see Fig. 10). When triggered either intrinsically (by contact with foreign surfaces ), or extrinsically (by tissue factors from damaged cells), inactive proenzymes (factors XII, XI, IX, and X) are transformed into activated pro-teinases (XHa, XIa, IXa, and Xa, respectively). Each proteinase catalyzes the activation of the following proenzyme in the sequence, up to formation of thrombin (Factor Ha), another proteinase that catalyzes partial... 

The discussion above of enzyme reactions treated the formation of the initial ES complex as an isolated equilibrium that is followed by slower chemical steps of catalysis. This rapid equilibrium model was first proposed by Henri (1903) and independently by Michaelis and Menten (1913). However, in most laboratory studies of enzyme reactions the rapid equilibrium model does not hold instead, enzyme... 

Equations (2.10) and (2.12) are identical except for the substitution of the equilibrium dissociation constant Ks in Equation (2.10) by the kinetic constant Ku in Equation (2.12). This substitution is necessary because in the steady state treatment, rapid equilibrium assumptions no longer holds. A detailed description of the meaning of Ku, in terms of specific rate constants can be found in the texts by Copeland (2000) and Fersht (1999) and elsewhere. For our purposes it suffices to say that while Ku is not a true equilibrium constant, it can nevertheless be viewed as a measure of the relative affinity of the ES encounter complex under steady state conditions. Thus in all of the equations presented in this chapter we must substitute Ku for Ks when dealing with steady state measurements of enzyme reactions. 

Let us consider an enzymatic reaction in which two substrates are utilized to from two products (in the nomenclature of enzyme reaction mechanisms this situation is referred to as a bi-bi mechanism). A reaction in which one substrate yields two products is referred to as a uni-bi mechanism, and one in which two substrates combine to form a single product is referred to as a bi-uni mechanism (see Copeland, 2000, for further details). For the purposes of illustration let us use the example of a group transfer reaction, in which a chemical species, X, is transferred from one substrate to the other in forming the products of the reaction ... 

Warshel A, Levitt M (1976) Theoretic studies of enzymic reactions dielectric electrostatic and steric stabilization if the carboniumion in the reaction of lysozyme. J Mol Bio 103 227... 

Zhang Y, Liu H, Yang W (2002) Ab initio QM/MM and free energy calculations of enzyme reactions. In Schlick T., Gan H. H., (ed) Methods for Macromolecular Modeling. Springer-Verlag Berlin, pp 332-354... 

Lack of perfect specificity in carrier-solute recognition provides for the possibility that structurally similar solutes may compete for carrier availability. Analysis of competitive [Eq. (18)] and noncompetitive [Eq. (19)] inhibition as well as cooperativity effects (allosteric modulation by structurally dissimilar solutes) on carrier-mediated solute flux is equivalent to assessment of the velocity of enzyme reactions. 

Methylcobalamin acts as the functional molecule for methyl-transfer in a second group of enzyme reactions. Theoretically methyl-transfer... 

During the second step, mevalonic acid is implicated in a number of enzymic reactions involving ATP, and is converted to isopentyl pyrophosphate and to its isomer 3,3-dimethylallyl pyrophosphate. Actually, the two compounds constitute the active isoprene , which... 

Cummins, P.L. Gready, J.E., Computational methods for the study of enzymic reaction mechanisms III a perturbation plus QM/MM approach for calculating relative free energies of protonation, J. Comp. Chem. 2005, 26, 561-568. 

Volume 354. Enzyme Kinetics and Mechanisms (Part F Detection and Characterization of Enzyme Reaction Intermediates)... 

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