Enzyme action mechanisms

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... 

Kinetics is the branch of science concerned with the rates of chemical reactions. The study of enzyme kinetics addresses the biological roles of enzymatic catalysts and how they accomplish their remarkable feats. In enzyme kinetics, we seek to determine the maximum reaction velocity that the enzyme can attain and its binding affinities for substrates and inhibitors. Coupled with studies on the structure and chemistry of the enzyme, analysis of the enzymatic rate under different reaction conditions yields insights regarding the enzyme s mechanism of catalytic action. Such information is essential to an overall understanding of metabolism. 

Living cells contain thousands of different kinds of catalysts, each of which is necessary to life. Many of these catalysts are proteins called enzymes, large molecules with a slotlike active site, where reaction takes place (Fig. 13.39). The substrate, the molecule on which the enzyme acts, fits into the slot as a key fits into a lock (Fig. 13.40). However, unlike an ordinary lock, a protein molecule distorts slightly as the substrate molecule approaches, and its ability to undergo the correct distortion also determines whether the key will fit. This refinement of the original lock-and-key model is known as the induced-fit mechanism of enzyme action. 

Biotransformation Conversion of a chemical into one or more products by a biological mechanism (predominantly by enzyme action). 

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. 

Inhibition Effects in Enzyme Catalyzed Reactions. Enzyme catalyzed reactions are often retarded or inhibited by the presence of species that do not participate in the reaction in question as well as by the products of the reaction. In some cases the reactants themselves can act as inhibitors. Inhibition usually results from the formation of various enzyme-inhibitor complexes, a situation that decreases the amount of enzyme available for the normal reaction sequence. The study of inhibition is important in the investigation of enzyme action. By determining what compounds behave as inhibitors and what type of kinetic patterns are followed, it may be possible to draw important conclusions about the mechanism of an enzyme s action or the nature of its active site. 

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. 

Electronically excited states of organic molecules, acid-base properties of, 12,131 Energetic tritium and carbon atoms, reactions of, with organic compounds, 2, 201 Enolisation of simple carbonyl compounds and related reactions, 18,1 Entropies of activation and mechanisms of reactions in solution, 1,1 Enzymatic catalysis, physical organic model systems and the problem of, 11, 1 Enzyme action, catalysis of micelles, membranes and other aqueous aggregates as models of, 17. 435... 

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). 

---