Enzyme chemistry

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An enzyme is characterized by having both a high degree of specificity and a high efficiency of reaction. The factors involved in enzyme-catalyzed reactions are the main subject of this chapter. 

For this, hydrolytic enzymes will be used to present the concept of the active site. However, an introduction to the general concepts of catalysis, which are based on transition state theory is needed first. Proximity and orientation of chemical groups will also be illustrated as factors responsible for the magnitude of enzyme catalysis. This will eventually allow the bridging of nonen-zymatic heterogeneous catalysis and enzymatic catalysis. 

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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. 

Suckling C. J. Molecular Recognition in Applied Enzyme Chemistry Experientia 1991 47 1139-1148... 

Kozarich JW (1988) Enzyme chemistry and evolution in the )S-ketoadipate pathway. In Microbial Metabolism and the Carbon Cycle (Eds SR Hagedorn, RS Hanson, and DA Kunz), pp. 283-302. Harwood Academic Publishers, Chur, Switzerland. 

More comprehensive accounts of enzyme chemistry, behaviour and technology are available [71,73-75]. In addition, general biochemistry textbooks contain more or less detailed accounts of these topics. 

One of the most important metals with regard to its role in enzyme chemistry is zinc. There are several significant enzymes that contain the metal, among which are carboxypeptidase A and B, alkaline phosphatase, alcohol dehydrogenase, aldolase, and carbonic anhydrase. Although most of these enzymes are involved in catalyzing biochemical reactions, carbonic anhydrase is involved in a process that is inorganic in nature. That reaction can be shown as... 

The transition between the two centuries also saw the discovery and development of two concepts essential to the further development of the understanding of soil chemistry. One was the discovery by J. J. Thomson of the electron, a subatomic particle. This work occurred around 1897 and culminated in the determination of the electron charge-to-mass ratio, which made it possible to develop the idea of ions [21], This was basic to the concept of ions discussed and developed by Svante Arrhenius in a series of lectures given at the University of California at Berkeley in 1907 [22], In this series of lectures, he clearly describes ions of hydrogen and chlorine. The basic idea of a hydrogen ion and its application to enzyme chemistry would be further developed by S. Sorenson [13],... 

This chapter describes a number of examples of kinetic isotope effects on chemical reactions of different types. These examples will be used to illustrate many aspects of the measurement, interpretation, and theoretical calculation of KIE s. Many of the examples are chosen from the field of organic chemistry. Chapter 11 deals with biochemistry, more specifically with enzyme chemistry. 

It is reasonable to expect that isotopic substitution on solvent molecules will affect both equilibrium and rate constants. This is especially true for reactions in aqueous media, many of which are acid or base catalyzed and therefore sensitive to pH or pD. Furthermore H/D aqueous solvent isotope effects often display significant nonlinearity when plotted against isotope fraction of the solvent. The analysis of this effect can yield mechanistic information. The study of aqueous solvent isotope effects is particularly important in enzyme chemistry because enzyme reactions universally occur in aqueous media and are generally pH sensitive. 

Multidomain synthetases can include specialized domains to modify the amino acids of peptide intermediates during chain elongation. The chemistry carried out by these domains introduces specific structural motifs, which are often important for biological activity, into the peptide natural product. A summary of additional NRPS enzyme chemistry is described below and illustrated in Figure 9. 

The schemes considered are only a few of the variety of combinations of consecutive first-order and second-order reactions possible including reversible and irreversible steps. Exact integrated rate expressions for systems of linked equilibria may be solved with computer programs. Examples other than those we have considered are rarely encountered however except in specific areas such as oscillating reactions or enzyme chemistry, and such complexity is to be avoided if at all possible. 

An alternative presentation of the mechanisms in (2.82)-(2.84) and (2.86)-(2.88) is shown in (2.91). This depiction is popular in the complex mechanisms encountered in metallo-enzyme chemistry. 

Brown BR, Bocks SM (1963) Some new enzymic reactions of phenols. In Pridham JB (ed) Enzyme chemistry of phenolic compounds. Pergamon Press, Oxford, p 129... 

Enzyme chemistry impact and applications. Chapman and HaU, London, p 50... 

The enzyme chemistry of cyclopropylmethanols has been studied both as inhibitors and mechanistic probes [4, 47]. Thus, a series of alkylcyclopropyl-methanol derivatives have been proved as being inhibitors of horse liver alcohol dehydrogenase. There are two sites in the cyclopropylmethanol inhibitors able of reacting with nucleophiles ... 

To understand the catalytic system under investigation as a whole, we tried to transfer experimental methods and the corresponding/orma/ism from inorganic chemistry (see Chap. 3) and enzyme chemistry to metal catalysis. To get an insight into the... 

The manifold intermediates in homogeneous transition-metal catalysis are certainly metal complexes and therefore show a behaviour like ordinary coordination compounds associations of phosphorus donors open up multifarious additional controls. Both, substrates and P ligands are Lewis bases that we have to consider and that compete at the coordination centers of the metal, leading to competitive, non-competitive or uncompetitive activation or inhibition processes in analogy to the terminology of enzyme chemistry... 

Rittenberg, D., Paper presented at International Conference on Enzyme Chemistry, Tokyo, 1957. 

Another line of evidence that supports this pathway comes from a consideration of stereochemistry. In 1953, D. E. Koshland Jr. pointed out the significance of the fact that the formation of glucose-1-phosphate [5] from sucrose [6] occurs with retention of configuration at C-l of the glucose moiety. He postulated that a single displacement, in enzymic chemistry as in... 

Enzyme chemistry, 291 Enzyme substrate, 291 Epoxides, reaction with sulfur dioxide, 78-79... 

An interesting variation of the latter technique finds application in enzyme chemistry. In this procedure a tissue section is exposed to a relatively colorless derivative of j8-naphthol, such as sodium j8-naphthyl acid phosphate. A phos-photase enzyme reacts with this reagent (often called an enzyme substrate ), leaving free j8-naphthol behind. Subsequent treatment with a solution of a diazonium salt produces highly colored spots in the tissue section. Thus not only can the presence of phosphotase enzyme be demonstrated, but also the location of the enzyme in the tissue can be determined. The intensity and chroma of the color produced and the solubility of the azo dye in the cell materials can be varied by judicious selection of the reagents. 

We present here the mechanisms for four enzymes chymotrypsin, hexoldnase, enolase, and lysozyme. These examples are not intended to cover all possible classes of enzyme chemistry. They are chosen in part because they are among the best understood enzymes, and in part because they clearly illustrate some general principles outlined in this chapter. The discussion concentrates on selected principles, along with some key experiments that have helped to bring these principles into focus. We use the chymotrypsin example to review some of the conventions used to depict enzyme mechanisms. Much mechanistic detail and experimental evidence is necessarily omitted no one book could completely document the rich experimental history of these enzymes. Also absent from these discussions is the special contribution of coenzymes to the catalytic activity of many enzymes. The function of coenzymes is chemically varied, and we describe each as it is encountered in Part II. 

A collection of classic papers on enzyme chemistry, with historical commentaries by the editor. Extremely interesting. 

N-acylimidazoles may be prepared269-271, and because of their relevance to enzyme chemistry (via histidine272) they have been the subject of much... 

An ideal test for measuring milk-clotting activity has never been devised, but numerous methods have been tried. In practice, activity is determined by the speed with which the enzyme clots milk under a set of specified conditions. This differs from the usual procedure in enzyme chemistry where one measures the rate at which the products of an enzyme-catalyzed reaction appear, or conversely, the rate at which the substrate disappears. 

Fukumoto, J., Tsujisaka, Y., Kimoto, K., Symp. Enzyme Chemistry, Fuku-... 

Many enzymes appear to be tailor-made for one specific reaction involving only one reactant, which is called the substrate. Others can function more generally with different reactants (substrates). But there is no such thing as a universal enzyme that does all things for all substrates. However, nothing seems to be left to chance even the equilibration of carbon dioxide with water is achieved with the aid of an enzyme known as carbonic anhydrase.8 Clearly, the scope of enzyme chemistry is enormous, yet the structure and function of relatively few enzymes are understood in any detail. We can give here only a brief discussion of the mechanisms of enzyme action—first some general principles then some specific examples. 

The use of substrate for adsorbent or support is to be discouraged because of its general use in enzyme chemistry to designate a reactant. 

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