Fundamentals of Biochemistry - A. A. Anisimov 1986

Enzymes
Classification and Nomenclature of Enzymes

According to the Classification developed by the International Commission on Enzymes and adopted in 1961, all enzymes are divided into six classes based on The Nature of the reactions they catalyze. These classes are subdivided into subclasses¹, and the latter into sub-subclasses or groups, within which enzymes are assigned an ordinal number. Each enzyme has its own unique four-digit code. For example, the code for glucose oxidase is EC 1.1.3.4, meaning it belongs to the first Class, the first subclass within that class, and the third sub-subclass, where it has the ordinal number 4. The classification is structured as follows.

¹ This section discusses the subclasses of the most frequently occurring enzymes.

1. Oxidoreductases. They catalyze oxidation-reduction (redox) reactions.

2. Transferases. They catalyze The transfer of functional groups from one molecule to another: XR + Z ⇄ X + RZ.

3. Hydrolases. They accelerate the hydrolytic Cleavage of chemical bonds: XY + H₂О = XОH + YH.

4. Lyases. They catalyze non-hydrolytic cleavage reactions resulting in The formation of double bonds, or addition reactions across double bonds¹.

5. Isomerases. They catalyze isomerization reactions within compounds.

6. Ligases (synthetases). They accelerate synthesis reactions coupled with the energy of high-energy (macroergic) compounds.

Rational, or systematic, enzyme names proposed by the International Commission include the names of the substrates and the Nature of the catalyzed reactions. Because rational names are quite cumbersome, working (trivial) names are also retained for enzymes. For example, The enzyme catalyzing the reaction ATP + hexose = hexose-6-phosphate + ADP has the working name hexokinase, whereas its rational name is ATP: D-hexose 6-phosphotransferase (in two-substrate reactions, the names of the substrates are separated by a colon). If an enzyme catalyzes a reaction involving two simultaneous transformations, the second transformation is indicated in parentheses in the enzyme's name. The reaction D-aspartate + H₂O + O₂ = oxaloacetate + NH₃ + H₂O is catalyzed by D-aspartate:oxygen oxidoreductase (deaminating)².

Class 1. Oxidoreductases. The systematic name of enzymes in this class is formed according to the scheme: hydrogen donor : acceptor oxidoreductase. Oxidoreductases that catalyze hydrogen transfer are trivially called dehydrogenases: R'Н₂ + R" = R''H₂ + R'. In cases where the exact hydrogen donor is not established, the term reductase is used. If O₂ serves as the hydrogen acceptor, the enzymes catalyzing these reactions are trivially called oxidases. Reactions Involving the direct addition of oxygen to a substrate are catalyzed by oxygenases. The term peroxidase refers to enzymes that use H₂O₂ as a hydrogen acceptor. Oxidoreductases are divided into 17 subclasses, primarily depending on which groups undergo oxidation—that is, the nature of the hydrogen Donors. The classification into subclasses, or groups, is based on the Chemical Nature of the hydrogen acceptor.

¹ Where the reverse reaction is significantly more important (или solely detected), the term synthase (rather than synthetase) may be used in the name. The term synthetase is recommended exclusively for Enzymes of the sixth class.

² In metabolic processes, organic acids and Amino Acids typically participate in the form of salts or in a dissociated state as anions; therefore, descriptions of reactions frequently use the names of anions rather than the acids themselves. For example: acetic acid — acetate, pyruvic acid — Pyruvate, succinic acid — succinate, aspartic acid — aspartate. In some cases, anion names are derived from the Latin or Greek names of the acids (acetate, succinate).

Subclass 1.1 includes enzymes acting on the CH–OH group of donors. An example of an enzyme in this subclass is Alcohol dehydrogenase. This group also includes LDH, MDH, phosphogluconate dehydrogenase (decarboxylating), and others.

Subclass 1.2 contains enzymes that oxidize the aldehyde or ketone group of donors.

Subclass 1.4 includes enzymes acting on the CH–NH₂ group of donors. This subclass comprises enzymes that catalyze the Oxidative Deamination of amino acids.

Subclass 1.6 comprises enzymes that oxidize reduced NAD and NADP, primarily represented by Flavoproteins.

Subclass 1.10 contains enzymes acting on diphenols and related compounds as donors. Ascorbate oxidase is a notable member of this subclass.

Subclass 1.11 includes enzymes that use hydrogen peroxide as an acceptor (catalase, peroxidase).

Subclass 1.13 contains enzymes acting on single donors with the incorporation of molecular oxygen (oxygenases).

Class 2. Transferases. The systematic name of enzymes in this class is formed as follows: donor : acceptor — transferred group — transferase. A numerical prefix is often used to indicate the position to which the transferred group is attached. Classification into subclasses is based on the chemical nature of the transferred groups, totaling eight subclasses.

2.1. Transfer one-carbon residues: methyl, hydroxymethyl, formyl, carboxyl, and others. Example: methyltransferases, which catalyze the transfer of methyl groups.

2.2. Transfer aldehyde and ketone residues. This group includes transketolase (which transfers a 2-carbon fragment) and transaldolase (which transfers a 3-carbon fragment). These enzymes participate in the Pentose Phosphate Pathway of Respiration and the photosynthetic Calvin cycle.

2.3. Acyltransferases — carriers of acid residues. This subclass includes A large number of enzymes that transfer acetyl residues from acetyl-CoA; such enzymes are trivially called acetyltransferases and participate, for example, in the synthesis of acetylglucosamine and acetylcholine.

2.4. Glycosyltransferases — carriers of glycosyl residues, such as enzymes involved in Polysaccharide synthesis that utilize a nucleoside diphosphate sugar (NDPS) as their non-protein moiety. The phosphorolytic cleavage of nucleosides also proceeds with the participation of these enzymes.

2.6. Transfer nitrogen-containing groups. This subclass includes the most important enzymes of Nitrogen METABOLISM — aminotransferases.

2.7. Transfer groups containing phosphorus (phosphotransferases). These enzymes transfer a phosphate group from ATP to various acceptors, a pyrophosphate group (pyrophosphotransferases), as well as more complex groups containing a phosphate group (nucleotidyltransferases, etc.).

2.8. Transfer sulfur-containing groups. This subclass includes, in particular, CoA-transferases.

Class 3. Hydrolases. The systematic name of an enzyme belonging to the class of hydrolases is formed from the substrate name followed by a hyphen and the word "Hydrolysis". The groups being cleaved can be specified after the substrate name, for example, adenosine aminohydrolase. The class of hydrolases is divided into eleven subclasses.

3.1. Hydrolyze ester bonds. Examples: esterases, Phosphatases, Nucleases.

3.2. Hydrolyze glycosidic bonds. Representatives of this subclass include amylases, chitinase, polygalacturonase, neuraminidase, a-glucosidase, ß-glucosidase, ß-fructofuranosidase (invertase).

3.4. Hydrolyze peptide bonds (peptide hydrolases). There is no systematic nomenclature for enzymes of this subclass because their specificities overlap. This subclass is divided into A number of sub-subclasses, specifically those cleaving N-terminal amino acids (aminopeptidases), C-terminal amino acids (Carboxypeptidases), those hydrolyzing dipeptides (dipeptidases), and several sub-subclasses of peptide hydrolases that break down Proteins (peptidyl peptide hydrolases, proteinases).

Proteinases are Endopeptidases that hydrolyze proteins into Peptides of various sizes. Depending on The Structure of the active center, the following subclasses of proteinases are distinguished.

3.4.21. Serine proteinases — contain serine in their active center, which is necessary for catalysis. These include Chymotrypsin, Trypsin (gastrointestinal proteinases), Thrombin, plasmin (Blood proteinases), and subtilisin (a proteolytic enzyme from *Bacillus subtilis*).

3.4.22. Thiol proteinases — contain Cysteine in their active center. These are predominantly plant proteinases, such as Papain from the milky juice of the melon tree. Certain tissue proteinases (cathepsin B, etc.) belong to this same structural type.

3.4.23. Acid proteinases — contain two carboxyl groups in their active center, with an optimal pH range for their activity from 1 to 5. This type includes Pepsin, rennin (chymosin), cathepsin D, and penicillopepsin.

3.4.24. Metalloproteinases.

3.4.99. Proteinases with an unknown catalytic mechanism.

3.5. Hydrolyze C—N bonds other than peptide bonds. In particular, this category includes enzymes that cleave amide bonds: asparaginase, glutaminase, urease.

3.6. Hydrolyze acid-anhydride bonds. This subclass includes inorganic pyrophosphatase and ATPases.

3.7. Hydrolyze C—C bonds. For instance, oxaloacetase, which accelerates the hydrolytic cleavage of oxaloacetate into oxalate and acetate.

Class 4. Lyases. The systematic names of enzymes in this class are formed from the substrate name, followed by the cleaved group, and the word "lyase" separated by a hyphen. The class is divided into seven subclasses.

4.1. C—C Lyases. This subclass includes fructose-bisphosphate aldolase, oxaloacetate decarboxylase, and aspartate 4-decarboxylase.

4.2. C—O Lyases. These include Carbonic anhydrase and fumarate hydratase.

4.3. C—N Lyases. For example, aspartate ammonia-lyase, which catalyzes the cleavage of aspartate into fumarate and ammonia.

5th class. Isomerases. The systematic name of enzymes in this class is formed according to the scheme: substrate-isomerization reaction type-isomerase. When groups are transferred intramolecularly, enzymes are given trivial names such as Mutases, while in reactions involving the inversion of groups at chiral centers, they are called racemases and epimerases.

Class 5 is divided into six subclasses.

5.1. Racemases and epimerases.

5.2. Cis-trans isomerases.

5.3. Intramolecular oxidoreductases. These enzymes catalyze the interconversion of aldoses and ketoses, ketone and enol groups, and shift C = C bonds. For example, in the D-glyceraldehyde-3-phosphate ⇄ dihydroxyacetone phosphate reaction, which is accelerated by D-glyceraldehyde-3-phosphate ketol-isomerase, reduction takes place at the first carbon atom of glyceraldehyde phosphate (GAP), while oxidation occurs at the second.

5.4. Intramolecular transferases. An example of an enzyme from this subclass is D-phosphoglycerate 2,3-phosphomutase, which catalyzes The conversion of 2-phospho-D-glycerate to 3-phospho-D-glycerate.

Grade 6. Ligases (synthetases). The systematic name is formed according to the scheme: A : B ligase (ADP-forming), where A and B are the joining molecules, and the name of the nucleoside triphosphate cleavage product used as an energy source in the reaction is indicated in parentheses. The entire class is divided into five subclasses depending on which atoms form the bonds.

6.1. Formation of C—O bonds. This type of bond is formed by the action of Aminoacyl-tRNA synthetases, which activate Amino Acids and transfer them to tRNA.

6.2. Formation of C—S bonds. Enzymes of this subclass catalyze the attachment of various acid residues to CoA.

6.3. Formation of C—N bonds. These enzymes are involved, for example, in the synthesis of various amides.

6.4. Formation of C—C bonds. This group includes carboxylases, which are biotin-containing enzymes.