Enzymes: Molecularity of Chemical Reaction and Reaction Kinetics

The metabolism of a cell is characterized by a myriad of simultaneously occurring chemical reactions.

Nearly all these reactions are catalyzed by a special class of proteins called enzymes. It has been esti­mated that the typical eukaryotic cell contains about 3000 different enzymes. In the absence of these en­zymes, most of the cellular reactions would proceed at much slower rates.

Enzymes integrate the cellular chemical reactions and provide the order without which the complex processes of life would not be possi­ble.

Most enzymes are characterized by a high degree of specificity; that is, they will catalyze one particular chemical reaction but not another. Enzyme molecules themselves are not consumed in the chemical reac­tions that they catalyze; instead, they become avail­able over and over again to repeatedly catalyze their reactions. More than a thousand different enzymes have been specifically identified, and of these, several hundred have already been isolated.

Most of the enzymes re­sponsible for such diverse functions as alimentary di­gestion, blood coagulation, muscle contraction, carbo­hydrate and lipid metabolism, and nucleic acid and protein biosynthesis are known. Before considering the properties of enzymes and the mechanisms of en­zymatic catalysis, some general features of chemical reactions will be reviewed.

Molecularity of Chemical Reactions:

Chemical reactions may be classified according to their level of molecularity; for example, monomolecular reactions, bimolecular reactions, tri-molecular re­actions, and so on. A monomolecular reaction may be written;

A ↔ P (8-1)

and involves the conversion of one molecular species (i.e., A) to another (i.e., P) without the addition or re­moval of atoms. Instead, an intra-molecular reorgani­zation of the molecule occurs. The inter-conversion of the α and β isomers of glucose via the open-chain in­termediate is an example of this type of reaction.

In the case just cited, the intra-molecular changes are spontaneous and do not require catalysis by an enzyme. In contrast, the conversion of glucose- 6-phosphate to fructose-6-phosphate during glycolysis (Fig. 8-1) is an example of an enzyme-catalyzed mono- molecular reaction. Enzymes catalyzing intra-molecu­lar reorganizations are called isomerases.

Monomolecular reactions are relatively uncommon in cells. Much more numerous are bimolecular reac­tions and reactions of higher order, involving two or more reactants and/or two or more products; for ex­ample,

Among the major classes of enzymes catalyzing bimolecular and higher-order reactions are the hydrolases, dehydrogenases, decarboxylases, and transferases. Hydrolases catalyze reactions in which water is either added to or removed from the reac­tants).

Dehydrogenases oxidize compounds by cata­lyzing the removal of hydrogen atoms. Decarboxy­lases remove carbon dioxide from carboxylic acids, and transferases remove reactive groups from one compound and transfer them to another. Numerous examples of these and other enzyme-catalyzed cellular reactions will be encountered in subsequent reading.

Reaction Kinetics:

To begin our consideration of the kinetics of chemical reactions, consider the reaction described by equation 8-2 in which A and B are the reactants and P is the single product of the reaction. One prerequisite for the reaction to occur is the “collision” of molecules A and B.

However, a collision alone is not sufficient to guarantee the formation of molecule P. In addition, molecules A and B must possess some minimal amount of kinetic energy at the instant of collision and must be oriented with respect to one another at that instant such that the chemical bonds strained by the collision allow the shifts of orbital electrons necessary for the formation of the product.

The probability of a reaction occurring between A and B is determined in part by the probability of find­ing molecules A and B in the same region of space at the same time (i.e., this would constitute a collision). The probability of finding molecule A in a specific re­gion of space is directly proportional to its concentra­tion, and the same is true for molecule B. Therefore, the probability of finding both molecules A and B in the same region of space at the same instant in time is equal to the product of the probabilities of each being there, that is,

Probability of collision ~ [A][B] (8-6)

Where [A] is the concentration of molecule A and [B] is the concentration of molecule B in the solution. The same line of reasoning leads us to conclude that the rate of the chemical reaction, that is, the change in the concentration of A and B with time as they are con­verted to P (i.e., d[A]/dt or d[B]/dt), would be directly proportional to the product of [A] and [B]. In a solution of any molecular species, not all the molecules will have the same kinetic energy. Instead, the energies are distributed as shown in Figure 8-2. This distribution, known as a Maxwell-Boltzmann dis­tribution, means that different molecules in the solu­tion have different kinetic energies.

This variation results from random collisions of the molecules with one another during which some molecules gain kinetic energy while others lose kinetic energy. For each chemical reaction, there is a minimum kinetic energy that the participating molecules must have for the chemical reaction to occur. As Figure 8-2 shows, only a small percentage of the molecules in solution have this energy at any instant in time (those to the right of E₁).

Even though a collision might involve two molecules with the required kinetic energies, it is still necessary that they be oriented with respect to one another in a specific manner at the instant of collision for the reac­tion to proceed. Thus, only a small percentage of the collisions involving molecules with the required ki­netic energy will result in the appropriate chemical reaction. Consequently, the actual rate at which the reaction takes place is equal to some constant, k₁ times the probability of a collision. This constant, called a rate constant, accounts for both molecular orientation and kinetic energy considerations. Thus,

Once a reversible reaction has reached equilibrium, no net change in the concentrations of the reactants or the produces) occurs. Therefore, at this time

Where K is the equilibrium constant for the reaction and describes the relative concentrations of all reacting molecular species at equilibrium.