Biochemical Foundations of Human Vital Activity - Volkov, N.I., Nesen, E.N. 2000

Biochemical Foundations of Human Vital Activity
Enzymes: Biological Catalysts
Mechanism of Enzyme Action

The primary condition for any chemical reaction is the interaction of reactant molecules. This can only occur if the molecules possess sufficient energy to overcome the energy barrier between them. The energy barrier is determined either by electrostatic repulsive forces between molecules or by cohesive forces between atoms within a molecule (the strength of chemical bonds). The higher the energy barrier, the slower the reaction proceeds. Only "activated" molecules—those with a sufficiently high activation energy capable of overcoming the reaction's energy barrier—enter into chemical reaction. Activation energy is the energy required for molecules to initiate a reaction.

In inanimate nature, molecule activation is achieved through heating (a 10 °C Temperature increase raises the reaction rate by a factor of 2–3), pressure elevation, irradiation, or the Introduction of a catalyst. In living organisms, substance transformation is accomplished by lowering the reaction's energy barrier through catalytic Enzymes. Enzymes interact with the substrate and decrease the activation energy required to trigger the reaction (Fig. 35).

According to modern concepts formulated in the works of V. Henri, L. Michaelis, M. Menten, and other scientists, the METABOLISM/10.html">Mechanism of enzyme-substrate interaction involves The formation of unstable enzyme-substrate complexes (ES). During the Formation of the enzyme-substrate complex, energy redistribution occurs within the substrate, leading to the Cleavage or formation of chemical bonds. For instance, the activation energy for the hydrolytic breakdown of sucrose without an enzyme is 134 kJ ∙ mol^-1 (25.6 kcal ∙ mol^-1), whereas in the presence of an enzyme (sucrase), it is only 39.3 kJ ∙ mol^-1 (8 kcal ∙ mol^-1).

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Fig. 35 Changes in the activation energy of reactants in non-enzymatic (1) and enzymatic (2) reactions

The process of enzyme-substrate interaction proceeds in several stages, as shown in Fig. 36. The primary stages are:

✵ interaction of the substrate (S) with the Active Site of the enzyme (E) and formation of the enzyme-substrate complex (ES);

✵ Conversion of the primary enzyme-substrate complex into other enzyme-substrate complexes (ES* and ES**), during which substances transition into an active state and subsequently dissociate into the enzyme and reaction products (P);

✵ dissociation of the reaction products from the enzyme's active site and their diffusion into the surrounding environment.

The equation representing Enzymatic Catalysis is written as

The enzyme itself remains unchanged during the reaction and can interact with new substrate molecules. For example, the Enzymatic Hydrolysis of ATP involving Ca²⁺-activated ATPase can be schematically represented as

Fig. 36 MAIN STAGES OF the enzyme-substrate interaction process

Enzyme-substrate interaction can occur only when the shape of the enzyme's active site corresponds to The Structure of the substrate molecule, i.e., when they exhibit high affinity. Several models explain The Mechanism of enzyme-substrate interaction. According to E. Fischer’s model, the active site of the enzyme has a rigid structure that precisely matches the STRUCTURE OF THE substrate molecule. The substrate molecule fits the enzyme's active site like a "lock and key" (Fig. 37, a). In accordance with D. Koshland’s "induced fit" (or "glove-hand") model, the enzyme's active site lacks a rigid conformation and is shaped by the substrate at the moment of their interaction, much like a glove that conforms to the shape of a hand (Fig. 37, b).

Fig. 37 Models of enzyme-substrate interaction: a — "rigid template" model by E. Fischer; b — "induced fit" model by D. Koshland