Classification of Enzymes

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Classification of Enzymes
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bind a specific substrate. Some enzymes have broad specificity; glucose, mannose, and fructose are phosphorylated by hexokinase, whereas glucokinase is specific for glucose. The substrate­binding site may contain the active site. In some cases, however, the active site may not be within the substrate­binding site but may be contiguous to it in the primary sequence. In other instances the active­site residues lie in distant regions of the primary sequence but are brought adjacent to the substrate­binding site by folding in the tertiary structure. The active site contains the machinery, in the form of particular amino acid side chains, involved in catalyzing the reaction.
Some enzymes have variants called isoenzymes (isozymes) that catalyze the same chemical reaction. Isoenzymes are electrophoretically distinguishable because of mutations in one or more amino acids in noncritical areas of the protein.
Some enzymes have a region of the molecule, the allosteric site, that is not at the active site or substrate­binding site but is a unique site where small molecules bind and effect a change in the substrate­binding site or the activity occurring in the active site. The binding of a specific small molecule at the allosteric site causes a change in the conformation of the enzyme. This can cause the active site to become either more active or less active by increasing or decreasing the affinity of the binding site for substrate. Such interactions regulate the enzyme's activity and are discussed in detail on page 151.
4.2— Classification of Enzymes
The International Union of Biochemistry and Molecular Biology (IUBMB) has established a system whereby all enzymes are classified into six major classes, each subdivided into subclasses that are further subdivided. In naming an enzyme, the substrates are stated first, followed by the reaction type to which the ending ­ase is affixed. For example, alcohol dehydrogenase is alcohol:NAD+ oxidoreductase because it catalyzes an oxidation–reduction reaction and the electron donor is an alcohol and the acceptor is NAD+. Many common names persist but are not very informative. For example, "aldolase" does not tell much about the substrates, although it does identify the reaction type. We will use trivial names recognized by the IUBMB and that are in common usage. Table 4.1 summarizes the six major classes and subclasses of enzymes.
Figure 4.1 Oxidation of ethanol by alcohol dehydrogenase.
Class 1— Oxidoreductases
These enzymes catalyze oxidation–reduction reactions. For example, alcohol:NAD+ oxidoreductase (alcohol dehydrogenase) catalyzes the oxidation of an alcohol to an aldehyde. It removes two electrons and two hydrogen atoms from the alcohol to yield an aldehyde, and, in the process, the two electrons originally in the carbon–hydrogen bond of the alcohol are transferred to the NAD+, which is reduced (Figure 4.1). NAD+, whose structure is presented in Figure 4.19, is a cofactor that mediates many biological oxidation–reduction reactions. The redox site in NAD+ is shown in Figure 4.20. In addition to the alcohol and aldehyde functional groups, dehydrogenases also act on the following functional groups as electron donors: –CH2–CH2–, –CH2–NH2, and –CH=NH, as well as the cofactors NADH and NADPH.
Figure 4.2 Oxidation of glucose by glucose oxidase.
There are other subclasses of the oxidoreductases. Oxidases transfer two electrons from the donor to oxygen, resulting usually in hydrogen peroxide (H2O2) formation. For example, glucose oxidase catalyzes the reaction shown in Figure 4.2. Cytochrome oxidase produces H2O rather than H2O2. Oxygenases catalyze the incorporation of oxygen into a substrate. With dioxygenases both atoms of O2 are incorporated in a single product, whereas with the monooxygenases a single oxygen atom is incorporated as a hydroxyl group
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TABLE 4.1 Summary of the Enzyme Classes and Major Subclasses
1. Oxidoreductases Dehydrogenases
Oxidases Reductases Peroxidases Catalase Oxygenases Hydroxylases
2. Transferases Transaldolase and transketolase Acyl, methyl, glucosyl, and phosphoryltransferase Kinases Phosphomutases
3. Hydrolases Esterases Glycosidases Peptidases Phosphatases Thiolases Phospholipases
Amidases Deaminases Ribonucleases
4.Lyases Decarboxylases
Aldolases Hydratases Dehydratases Synthases Lyases
5. Isomerases Racemases Epimerases Isomerases Mutases (not all)
6. Ligases Synthetases Carboxylases
Figure 4.3 Oxygenation of catechol by an oxygenase.
and the other oxygen atom is reduced to water by electrons from the substrate or from a second substrate that is not oxygenated. Catechol oxygenase catalyzes the dioxygenase reaction (Figure 4.3); steroid hydroxylase illustrates a monooxygenase (mixed function oxygenase) reaction (Figure 4.4). Peroxidases utilize H2O2 rather than oxygen as the oxidant. NADH peroxidase catalyzes the reaction
Figure 4.4 Hydroxylation of progesterone by a monooxygenase.
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Catalase is unique in that H2O2 serves as both donor and acceptor. Catalase functions in the cell to detoxify H2O2:
Class 2— Transferases
These enzymes transfer functional groups between donors and acceptors. The amino, acyl, phosphate, one­carbon, and glycosyl groups are the major moieties that are transferred. Aminotransferases (transaminases) transfer an amino group from one amino acid to an a ­keto acid acceptor, resulting in the formation of a new amino acid and a new keto acid (Figure 4.5). Kinases are the phosphorylating enzymes that catalyze the transfer of the g phosphoryl group from ATP or another nucleoside triphosphate to alcohol or amino group acceptors. For example, glucokinase catalyzes the phosphorylation of glucose (Figure 4.6).
Figure 4.5 Examples of a reaction catalyzed by an aminotransferase.
Figure 4.6 Phosphorylation of glucose by a kinase.
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Figure 4.7 A transferase reaction—synthesis of glycogen.
Glycogen synthesis depends on glucosyltransferases, which transfer an activated glucosyl residue to a glycogen primer. The phosphoester bond in uridine diphosphoglucose is labile, which allows the glucose to be transferred to the growing end of the glycogen primer as indicated in Figure 4.7.
Although a polymer is synthesized, the reaction is not of the ligase type reaction; see Class 6.
Class 3— Hydrolases
This group of enzymes can be considered as a special class of the transferases in which the donor group is transferred to water. The generalized reaction involves the hydrolytic cleavage of C–O, C–N, O–P, and C–S bonds. The cleavage of a peptide bond is a good example of this reaction:
Proteolytic enzymes are a special class of hydrolases called peptidases.
Class 4— Lyases
Lyases add or remove the elements of water, ammonia, or carbon dioxide. Decarboxylases remove the element of CO2 from a ­ or b ­keto acids or amino acids:
Dehydratases remove H2O in a dehydration reaction. Fumarase converts fumarate to malate (Figure 4.8).
Figure 4.8 The fumarase reaction.
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