Mechanism, reaction Briggs-Haldane

A mathematical equation indicating how the equilibrium constant of an enzyme-catalyzed reaction (or half-reaction in the case of so-called ping pong reaction mechanisms) is related to the various kinetic parameters for the reaction mechanism. In the Briggs-Haldane steady-state treatment of a Uni Uni reaction mechanism, the Haldane relation can be written as follows ... 

Figure 8.1 Model energy diagrams for non-enzymic reactions (A), enzymic reaction following the rapid equilibrium mechanism (see Table 8.1) (B) and enzymic reaction following Briggs-Haldane kinetics (C). E represents the activation energy of transition and the positive and...

The result of equation 3.39 for nonproductive binding is quite general. It applies to cases in which intermediates occur on the reaction pathway as well as in the nonproductive modes. For example, in equation 3.19 for the action of chy-motrypsin on esters with accumulation of an acylenzyme, it is seen from the ratios of equations 3.21 and 3.22 that kQJKM = k2IKs. This relationship clearly breaks down for the Briggs-Haldane mechanism in which the enzyme-substrate complex is not in thermodynamic equilibrium with the free enzyme and substrates. It should be borne in mind that KM might be a complex function when there are several enzyme-bound intermediates in rapid equilibrium, as in equation 3.16. Here kcJKM is a function of all the bound species. 

The Michaelis- Menten (Briggs- Haldane) mechanism in enzyme kinetics is based upon the following reaction scheme between the reactant (substrate S), and the catalyst (enzyme ) to give the product, P ... 

The earher recommendation of the Enz5nne Commission of the International Union of Biochemistry was that the Ks should be apphed for the Michaelis-Menten mechanism and Ku for the Briggs-Haldane mechanism (Enzyme Nomenclature, 1973) in this case, /Cm = Jfs + k /kf This practice must be discouraged because it leads to cumbersome and ambiguous expressions in multisubstrate reactions. 

AH enz5nnatic reactions are in principle reversible, in a sense that significant amounts of both substrates and products exist in the equilibrium mixture (Albeity, 1959 Cleland, 1970 Plowman, 1972). Therefore, it is evident that both Michaehs-Menten and Briggs-Haldane mechanisms are incomplete, and that allowance must be made for the reverse reaction ... 

At low substrate concentrations, the enzyme is largely unbound and E Eo therefore, fccat/ A is an apparent second-order rate constant, which is not a tme microscopic rate constant except in the extreme case in which the rate-limiting step in the reaction is the encounter of enzyme and substrate. Only in the Briggs-Haldane mechanism, when is much greater than fc, fccat/JSC is equal to ku the rate constant for the association of enzyme and substrate. Recently, Northrop (1999) raised a serious objection to this classical definition of the specificity constant, and pointed out that fcc t/ 0 actually provides a measure of the rate of capture of substrate by free enzyme into a productive complex or complexes destined to go on to form products and complete a turnover at some later time. 

The kinetics of the general enzyme-catalyzed reaction (equation 10.1-1) may be simple or complex, depending upon the enzyme and substrate concentrations, the presence/absence of inhibitors and/or cofactors, and upon temperature, shear, ionic strength, and pH. The simplest form of the rate law for enzyme reactions was proposed by Henri (1902), and a mechanism was proposed by Michaelis and Menten (1913), which was later extended by Briggs and Haldane (1925). The mechanism is usually referred to as the Michaelis-Menten mechanism or model. It is a two-step mechanism, the first step being a rapid, reversible formation of an enzyme-substrate complex, ES, followed by a slow, rate-determining decomposition step to form the product and reproduce the enzyme ... 

A reactant in an enzyme catalysed reaction is known as substrate. According to the mechanism of enzyme catalysis, the enzyme combines with the substrate to form a complex, as suggested by Henri (1903). He also suggested that this complex remains in equilibrium with the enzyme and the substrate. Later on in 1925, Briggs and Haldane showed that a steady state treatment could be easily applied to the kinetics of enzymes. Some photochemical reactions and some enzymic reactions are reactions of the zero order. 

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