Enzyme-catalyzed reactions activity

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

Enzymes are basically specialty proteins (qv) and consist of amino acids, the exact sequence of which determines the enzyme stmcture and function. Although enzyme molecules are typically very large, most of the chemistry involving the enzyme takes place in a relatively small region known as the active site. In an enzyme-catalyzed reaction, binding occurs at the active site to one of the molecules involved. This molecule is called the substrate. Enzymes are... 

Inhibition The decrease of the rate of an enzyme-catalyzed reaction by a chemical compound including substrate analogues. Such inhibition may be competitive with the substrate (binding at die active site of die enzyme) or non-competitive (binding at an allosteric site). 

Like most chemical reactions, the rates of enzyme-catalyzed reactions generally increase with increasing temperature. However, at temperatures above 50° to 60°C, enzymes typically show a decline in activity (Figure 14.12). Two effects are operating here (a) the characteristic increase in reaction rate with temperature, and (b) thermal denaturation of protein structure at higher tem-... 

FIGURE 16.1 Enzymes catalyze reactions by lowering the activation energy. Here the free energy of activation for (a) the uncatalyzed reaction, AGu, is larger than that for (b) the enzyme-catalyzed reaction, AG,". 

FIGURE 6-3 Dependence of the velocity of an enzyme-catalyzed reaction upon the substrate concentration (at a constant level of enzyme activity). 

Information relevant to the mechanism of an enzyme-catalyzed reaction can, in general, only be obtained from irreversible inhibitors which react specifically at the active site and thereby inactivate the enzyme. As active-site-directed inhibition is treated in detail in Ref. 142 general aspects will be discussed here only briefly. In order to be suitable as an active-site-directed inhibitor, a compound must fulfil the following requirements. 

Reactions proceed via transition states in which AGp is the activation energy. Temperature, hydrogen ion concentration, enzyme concentration, substrate concentration, and inhibitors all affect the rates of enzyme-catalyzed reactions. 

Figure 15-8. Mechanisms of control of an enzyme-catalyzed reaction. Circled numbers indicate possible sites of action of hormones. .Alteration of membrane permeability conversion of an inactive to an active enzyme, usually in-...

In prokaryotes, each reaction of Figure 34-2 is catalyzed by a different polypeptide. By contrast, in eukaryotes, the enzymes are polypeptides with multiple catalytic activities whose adjacent catalytic sites facilitate channeling of intermediates between sites. Three distinct multifunctional enzymes catalyze reactions 3, 4, and 6, reactions 7 and 8, and reactions 10 and 11 of Figure 34-2. 

Five of the first six enzyme activities of pyrimidine biosynthesis reside on multifunctional polypeptides. One such polypeptide catalyzes the first three reactions of Figure 34-2 and ensures efficient channeling of carbamoyl phosphate to pyrimidine biosynthesis. A second bifunctional enzyme catalyzes reactions 5 and 6. 

Monitoring enzyme catalyzed reactions by voltammetry and amperometry is an extremely active area of bioelectrochemical interest. Whereas liquid chromatography provides selectivity, the use of enzymes to generate electroactive products provides specificity to electroanalytical techniques. In essence, enzymes are used as a derivatiz-ing agent to convert a nonelectroactive species into an electroactive species. Alternatively, electrochemistry has been used as a sensitive method to follow enzymatic reactions and to determine enzyme activity. Enzyme-linked immunoassays with electrochemical detection have been reported to provide even greater specificity and sensitivity than other enzyme linked electrochemical techniques. 

From Equation (2.4) we see that the overall activation energy for the enzyme-catalyzed reaction is related to the second-order rate constant defined by the ratio... 

Figure 2.1 Free energy diagram for the reaction pathway of a chemical reaction, and the same reaction catalyzed by an enzyme. Note the significant reduction in activation energy (the vertical distance between the reactant state and the transition state) achieved by the enzyme-catalyzed reaction.

In this chapter we have seen that enzymatic catalysis is initiated by the reversible interactions of a substrate molecule with the active site of the enzyme to form a non-covalent binary complex. The chemical transformation of the substrate to the product molecule occurs within the context of the enzyme active site subsequent to initial complex formation. We saw that the enormous rate enhancements for enzyme-catalyzed reactions are the result of specific mechanisms that enzymes use to achieve large reductions in the energy of activation associated with attainment of the reaction transition state structure. Stabilization of the reaction transition state in the context of the enzymatic reaction is the key contributor to both enzymatic rate enhancement and substrate specificity. We described several chemical strategies by which enzymes achieve this transition state stabilization. We also saw in this chapter that enzyme reactions are most commonly studied by following the kinetics of these reactions under steady state conditions. We defined three kinetic constants—kai KM, and kcJKM—that can be used to define the efficiency of enzymatic catalysis, and each reports on different portions of the enzymatic reaction pathway. Perturbations... 

Most biological reactions fall into the categories of first-order or second-order reactions, and we will discuss these in more detail below. In certain situations the rate of reaction is independent of reaction concentration hence the rate equation is simply v = k. Such reactions are said to be zero order. Systems for which the reaction rate can reach a maximum value under saturating reactant conditions become zero ordered at high reactant concentrations. Examples of such systems include enzyme-catalyzed reactions, receptor-ligand induced signal transduction, and cellular activated transport systems. Recall from Chapter 2, for example, that when [S] Ku for an enzyme-catalyzed reaction, the velocity is essentially constant and close to the value of Vmax. Under these substrate concentration conditions the enzyme reaction will appear to be zero order in the substrate. 

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. 

Biihler, H., Bayer, A. and Effenberger, F. (2000) Enzyme-catalyzed reactions, part 39. A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4-hydroxy-2(5f/)-furanones from (5)-ketone cyanohydrins. Chemistry - A European Journal, 6, 2564—2571. 

---