Energy enzyme-substrate complex

Figure 1.1 Energy diagram for an enzyme-catalyzed enantioselective reaction. E = enzyme A and B = enantiomeric substrates P and Q = enantiomeric products [EA] and [EB] = enzyme-substrate complexes AAC = difference in free energy denotes a transition state.

Later on12, Koshland proposed the induced fit model of the active site action that considers that during the formation of the enzyme-substrate complex, the enzyme can change its conformation so as to wrap the substrate like it happens when a hand (substrate) fits in a globe (enzyme). This flexing puts the active site and bonds in the substrate under strain, which weakens the bonds and helps to lower the activation energy for the catalyzed reaction. 

CoA, the coenzyme A derivative of acetoacetate, reduces its reactivity as a substrate for /3-ketoacyl-CoA transferase (an enzyme of lipid metabolism) by a factor of 106. Although this requirement for adenosine has not been investigated in detail, it must involve the binding energy between enzyme and substrate (or cofactor) that is used both in catalysis and in stabilizing the initial enzyme-substrate complex (Chapter 6). In the case of /3-ketoacyl-CoA transferase, the nucleotide moiety of coenzyme A appears to be a binding handle that helps to pull the substrate (acetoacetyl-CoA) into the active site. Similar roles may be found for the nucleoside portion of other nucleotide cofactors. 

Schematic representation of energy changes accompanying formation of enzyme-substrate complex and subsequent formation of a transition-state complex.

Here the full binding energy AGb is realized only in the transition state. The adverse energy term AGR in the initial enzyme-substrate complex will increase Km, but the gain in binding energy as the reaction reaches the transition state will increase kcat. Thus,... 

The rate of reaction at low substrate concentration is proportional to the saturation rate, kB, and concentration of the array of enzyme-substrate complexes, which is proportional to l/Km thus, the rate is proportional to ks/Km. Since stabilization of the complex by changing pH, for example, increases the concentration of the complex at the same time as it decreases the probability of activation to a transition state, the net result is that k /Km is related to the free energy of the activated complex relative to the unbound enzyme, an unbound substrate. The pH profile of ke/Km thus potentially reveals the pK values of groups on the free enzyme and free substrate that are involved significantly in rate limiting processes. This well-known relationship has been used to establish the pIC values of 5.4 and 6.4 for groups on the enzyme in 0.2 M KC1 for both... 

Concentration of A Arrhenius constants Arrhenius constant Constant in equation 5.82 Surface area per unit volume Parameter in equation 5.218 Cross-sectional area Concentration of B Stoichiometric constants Parameter in equation 5.218 Concentration of gas in liquid phase Saturation concentration of gas in liquid Concentration of G-mass Concentration of D-mass Dilution rate DamkOhler number Critical dilution rate for wash-out Effective diffusion coefficient Dilution rate for maximum biomass production Dilution rate for CSTF 1 Dilution rate for CSTF 2 Activation energy Enzyme concentration Concentration of active enzyme Active enzyme concentration at time t Initial active enzyme concentration Concentration of inactive enzyme Total enzyme concentration Concentration of enzyme-substrate complex with substance A... 

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