The Mechanism of Enzyme Action

Averbukh I Sh, Blumenfeld L A, Kovarsky V A and Perelman N F 1986 A model of the mechanism of enzyme action in terms of protein conformational relaxation Blochim. Blophys. Acta. 873 290-6... 

Site-directed mutagenesis, used to change residues suspected of being important in catalysis or substrate binding, provides insights into the mechanisms of enzyme action. 

Inhibitors of the catalytic activities of enzymes provide both pharmacologic agents and research tools for study of the mechanism of enzyme action. Inhibitors can be classified based upon their site of action on the enzyme, on whether or not they chemically modify the enzyme, or on the kinetic parameters they influence. KineticaUy, we distinguish two classes of inhibitors based upon whether raising the substrate concentration does or does not overcome the inhibition. 

Uraki, Z., Terminiello, L., Bier, M., and Nord, F.F. (1957) On the mechanism of enzyme action. LXIII. Specificity of acetylation of proteins with C14 anhydride. Arch. Biochem. Biophys. 69, 644-652. 

Smith, V. M. On the Mechanism of Enzyme Action. XXXVI. Dehydrogenation Studies on Merulius lacrymans and Marasmius chordalis and the Mechanism of Oxalic Acid Formation. Arch. Biochem. 22, 275 (1949). 

V3. Vennesland, B., and Westheimer, F. H., Hydrogen transport and steric specificity in reactions catalyzed by pyridine nucleotide dehydrogenases. In The Mechanism of Enzyme Action (W. D. McElroy, and B. Glass, eds.), pp. 357-379. Johns Hopkins Press, Baltimore, Maryland, 1954. 

The mechanism of enzyme action can be viewed from two different perspectives. The first treats catalysis in terms of energy changes that occur during the reaction, that is, enzymes provide an alternate, energetically favorable reaction pathway different from the uncatalyzed reaction. The second perspective describes how the active site chemically facilitates catalysis. 

Nonsubstrate molecules may interact with enzymes, leading to a decrease in enzymatic activity. The study of enzyme inhibition is of interest because it often reveals information about the mechanism of enzyme action. Also, many toxic substances, including drugs, express their action by enzyme inhibition. 

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. 

Enzyme kinetics is studied for two reasons (1) it is a practical concern to determine the activity of the enzyme under different conditions (2) frequently the analysis of enzyme kinetics gives information about the mechanism of enzyme action. Chapter 7, Enzyme Kinetics, begins with an introductory section on the discovery of enzymes, basic enzyme terminology and a description of the six main classes of enzymes and the reactions they catalyze. The remainder of the chapter deals with basic aspects of chemical kinetics, enzyme-catalyzed reactions and various factors that affect the kinetics. 

At present, for the creation of completely new chemical systems, chemists adopt the principles of natural chemical reactions from nature. That is why for thriving chemical bionics such as chemical modeling methods for natural chemical processes, as well as the use of structure modeling technique, active sites and the mechanism of enzymes action, the conjugation principles of biochemical processes are used. 

Another of Conant s students was Frank Westheimer (b. 1912), who, after postdoctoral work with Hammett at Columbia, held a post at the University of Chicago (1936-1954) and then returned to Harvard. Westheimer worked in several areas of physical organic chemistry and engaged in other chemistry-based activities, as revealed in an interview conducted in 1995 by Istvan Hargittai.233 For much of his career, Westheimer was essentially a physical organic chemist working in biochemistry and he has himself written reflectively on the discovery of the mechanisms of enzyme action over the period 1947-1963234 and on the application of physical organic chemistry to biochemical problems.235 Westheimer has also contributed, as Tetrahedron Perspective Number 4, an article on Coincidences, decarboxylation, and electrostatic effects , which, he writes, ...allows me to review some of my past .236... 

Extrinsic cotton effects and the mechanism of enzyme action. Advan. 

Directive effects in aromatic substitution, a quantitative treatment of, 1, 35 Directive effects in gas-phase radical addition reactions, 16, 51 Discovery of the mechanisms of enzyme action, 1947-1963, 21, 1 Displacement reactions, gas-phase nucleophilic, 21, 197... 

A quarter of a century has passed since the first contribution on catalase to The Enzymes Enzyme substrate compounds Mechanism of action of hydroperoxidases (I). In this perspective, we can identify a sequence of steps in the development of ideas on the mechanism of enzymic action and the nature of enzyme-substrate compounds. The identification of these compounds and the approach to enzymic reactions at concentrations stoichiometric with the substrate caused a principal transition of viewpoint on hemoprotein catalysis from free radical mechanisms (2) unrelated to an active center toward the acceptance of catalysis occurring at the iron atom of the porphyrin (S-5). The latter concept followed natu-... 

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