Enzymic activity in some cases relies on nonproteins. An active enzyme along with its nonprotein component is known as a holoenzyme, while an inactive enzyme without its nonprotein moiety is called an apoenzyme. If the nonprotein moiety consists of a metal ion, such as zinc (Zn2+) or iron (Fe2+), it is referred to as a cofactor. If it is a small organic molecule, it is termed a coenzyme. Coenzymes that only temporarily associate with the enzyme are called cosubstrates, which dissociate from the enzyme in an altered state (e.g. NAD+). On the other hand, if the coenzyme is permanently associated with the enzyme and returns to its original form, it is called a prosthetic group (e.g. FAD). Coenzymes are often derived from vitamins, for example, NAD+ contains niacin, and FAD contains riboflavin.

Enzyme activity can be regulated, either increased or decreased, to meet the cellular requirements for product formation.

Many enzymes are localized in specific organelles within the cell to isolate the reaction substrate or product from other competing reactions. This localization provides a favorable environment for the reaction and organizes the numerous enzymes present in the cell into purposeful pathways.

The mechanism of enzyme action can be understood from two perspectives. The first perspective focuses on the energy changes that occur during the reaction. Enzymes provide an alternate, energetically favorable reaction pathway different from the uncatalyzed reaction. The second perspective describes how the active site of the enzyme chemically facilitates catalysis.

Chemical reactions typically have an energy barrier known as the activation energy (Ea) that separates the reactants from the products. This energy barrier represents the difference in energy between the reactants and a high-energy intermediate called the transition state (T*). Uncatalyzed chemical reactions are often slow due to the high activation energy. To achieve the transition state and react, molecules need to possess sufficient energy. In the absence of an enzyme, only a small proportion of molecules may have enough energy to reach the transition state. The rate of reaction depends on the number of such energized molecules. A lower activation energy allows more molecules to have sufficient energy to pass through the transition state, resulting in a faster reaction rate.

Enzymes facilitate rapid reactions under cellular conditions by providing an alternate reaction pathway with a lower activation energy. Enzymes do not alter the free energies of the substrates or products, thus not affecting the reaction equilibrium. However, they accelerate the rate at which equilibrium is achieved.

The active site of an enzyme is not merely a passive binding site for the substrate. Instead, it acts as a complex molecular machine utilizing various chemical mechanisms to facilitate the conversion of substrate to product. Several factors contribute to the catalytic efficiency of enzymes.
Some enzymes require nonproteins for enzymic activity. The term holoenzyme refers to the active enzyme with its nonprotein component, whereas the enzyme without its nonprotein moiety is termed an apoenzyme and is inactive. If the nonprotein moiety is a metal ion, such as zinc (Zn2+) or iron (Fe2+), it is called a cofactor (see Chapter 29). If it is a small organic molecule, it is termed a coenzyme. Coenzymes that only transiently associate with the enzyme are called cosubstrates. Cosubstrates dissociate from the enzyme in an altered state (NAD+ is an example; see p. 101). If the coenzyme is permanently associated with the enzyme and returned to its original form, it is called a prosthetic group (FAD is an example; see p. 110). Coenzymes commonly are derived from vitamins. For example, NAD+ contains niacin, and FAD contains riboflavin (see Chapter 28).
E. Regulation
Enzyme activity can be regulated, that is, increased or decreased, so that the rate of product formation responds to cellular need.
F. Location within the cell
Many enzymes are localized in specific organelles within the cell (Fig. 5.3). Such compartmentalization serves to isolate the reaction substrate or product from other competing reactions. This provides a favorable environment for the reaction and organizes the thousands of enzymes present in the cell into purposeful pathways.
IV. MECHANISM OF ENZYME ACTION
The mechanism of enzyme action can be viewed from two different perspectives. The first treats catalysis in terms of energy changes that occur during the reaction. That is, enzymes provide an alternate, energetically favorable reaction pathway different from the uncatalyzed reaction. The second perspective describes how the active site chemically facilitates catalysis.
A. Energy changes occurring during the reaction
Virtually all chemical reactions have an energy barrier separating the reactants and the products. This barrier, called the activation energy (Ea), is the energy difference between that of the reactants and a high-energy intermediate, the transition state (T*), which is formed during the conversion of reactant to product. Figure 5.4 shows the changes in energy during the conversion of a molecule of reactant A to product B as it proceeds through the transition state.
1.
Activation energy: The peak of energy in Figure 5.4 is the difference in free energy between the reactant and T*, in which the high-energy, short-lived intermediate is formed during the conversion of reactant to product. Because of the high Ea, the rates of uncatalyzed chemical reactions are often slow.
2.
Rate of reaction: For molecules to react, they must contain sufficient energy to overcome the energy barrier of the transition state. In the absence of an enzyme, only a small proportion of a population of molecules may possess enough energy to achieve the transition state between reactant and product. The rate of reaction is determined by the number of such energized molecules. In general, the lower the Ea, the more molecules have sufficient energy to pass through the transition state and, therefore, the faster the rate of the reaction.
3.
Alternate reaction pathway: An enzyme allows a reaction to proceed rapidly under conditions prevailing in the cell by providing an alternate reaction pathway with a lower Ea (see Fig. 5.4). The enzyme does not change the free energies of the reactants (substrates) or products and, therefore, does not change the equilibrium of the reaction (see p. 70). It does, however, accelerate the rate by which equilibrium is reached.
B. Active site chemistry
The active site is not a passive receptacle for binding the substrate but, rather, is a complex molecular machine employing a diversity of chemical mechanisms to facilitate the conversion of substrate to product. A number of factors are responsible for the catalytic efficiency of enzymes, including the following examples.
1.