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Scheme 1.3 A generalized enzyme‐catalyzed reaction.

Table 1.1 Turnover numbers for some enzymes.

1.3 Cofactors and Coenzymes

Enzymes have protein nature and molecular weights ranging from about 12 000 to over 1 million. The large molecule of enzymes is flexible for binding natural and unnatural substrates at their active site. The active site contains moieties consisted with amino acid residues. Although the activity of some enzymes requires no chemical groups other than their amino acid residues, others require an additional chemical component called cofactor. A cofactor, also called a coenzyme, is either one or more inorganic ions, such as Fe²⁺, Mg²⁺, Mn²⁺, or Zn²⁺ (Table 1.2) [9], or an organic or metallo‐organic molecule. Coenzyme are often derived from vitamins and organic nutrients required in small amounts in the diet (Table 1.3) [9]. The cofactor binds to the active site, in some cases covalently and in others noncovalently, which serves as transient carriers of redox equivalents, such as NAD(P)H or chemical energy (ATP) and is essential for the catalytic action of those enzymes that require cofactors.

Table 1.2 Some inorganic metal ions as cofactor of enzymes.

      Source: Based on Nelson and Cox [9].

Table 1.3 Some coenzymes as transient carriers of specific atoms or functional groups.

      Source: Based on Nelson and Cox [9].

      For some enzymes, a coenzyme is required for their activity. A coenzyme or metal ion that is bound to the enzyme protein at the active site is called a prosthetic group. The protein part of such an enzyme is called the apoenzyme or apoprotein, and the entire enzyme is called a holoenzyme. Most of these cofactors are relatively unstable molecules. We will consider various coenzymes throughout the text in more detail for those related enzyme‐catalyzed reactions.

1.4 Molecular Recognition and Enzyme Specificity

The science by which molecules interact via geometric orientations of atoms is called molecular recognition. The specific geometry of a molecule controls how it will react with other substances. Nearly, all enzymes are made up of more than 100 amino acid residues. However, an enzyme binds a substrate molecule at the catalytic active site that is just a small pocket or cleft region of the enzyme. The 3D structure of the active site is surrounded by amino acid side chains that come from different parts of the linear amino acid sequence. Water is usually excluded unless it is a reactant. The nonpolar character of much of the cleft enhances the binding of substrate. However, the cleft may also contain some polar residues that create a microenvironment essential for catalysis and extraordinary enzyme specificity. The specificity of binding of atoms in a substrate to the active site leads the proposed lock‐and‐key model of interaction between the substrate and enzyme by Emil Fischer in 1894 that points out the binding of a substrate to an enzyme just like the relationship of a key to a lock. The lock‐and‐key model is now modified to the induced fit model by Daniel Koshland in 1958 with the evident that the enzyme and substrate must adjust to fit one another to take up a configuration to stabilize the transition state [10, 11].

      However, to assure the necessary geometric accuracy of the substrate binding and the orientation of catalytic functional group for enzyme interaction, the number of specific binding sites or points needed between the substrate and the active site of enzyme depends on the size of a molecule. For a large molecule such as glycyl tyrosine, a dipeptide, can bind carboxypeptidase A through total of five points at the active site [10, 12]: the electrostatic force, two hydrogen bonds, the hydrophobic interaction, and

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