Classification of Enzymes

Based on catalyzed reactions, the nomenclature committee of the International Union of Biochemistry and Molecular Biology (IUBMB) recommended the following classification.

1. Oxidoreductases catalyze a variety of oxidation-reduction reactions.  Common names include dehydrogenase, oxidase, reductase and catalase.

2. Transferases catalyze transfers of groups (acetyl, methyl, phosphate, etc.).  Common names include acetyltransferase, methylase, protein kinase and polymerase. The first three subclasses play major roles in the regulation of cellular processes.  Their chemical reactions are shown in Figure 2-E-1.  The polymerase is essential for the synthesis of DNA and RNA.

3. Hydrolases catalyze hydrolysis reactions where a molecule is split into two or more smaller molecules by the addition of water.  Common examples are given below.

Proteases splits protein molecules.  Examples: HIV protease and caspase.  HIV protease is essential for HIV replication.  Caspase plays a major role in apoptosis.

Nucleases splits nucleic acids (DNA and RNA).  Based on the substrate type, they are divided into RNase and DNase.  RNase catalyzes the hydrolysis of RNA and DNase acts on DNA.  They may also be divided into exonuclease and endonuclease.  The exonuclease progressively splits off single nucleotides from one end of DNA or RNA.  The endonuclease splits DNA or RNA at internal sites.

Phosphatase catalyzes dephosphorylation (removal of phosphate groups).  Example: calcineurin.   The immunosuppressive drugs FK506 and Cyclosporin A are the inhibitors of calcineurin.

4. Lyases catalyze the cleavage of C-C, C-O, C-S and C-N bonds by means other than hydrolysis or oxidation.  Common names include decarboxylase and aldolase.

5. Isomerases catalyze atomic rearrangements within a molecule.  Examples include rotamase, protein disulfide isomerase (PDI), epimerase and racemase.

6. Ligases catalyze the reaction which joins two molecules.  Examples include peptide synthase, aminoacyl-tRNA synthetase, DNA ligase and RNA ligase.

The IUBMB committee also defines subclasses and sub-subclasses.  Each enzyme is assigned an EC (Enzyme Commission) number.  For example, the EC number of catalase is EC1.11.1.6.  The first digit indicates that the enzyme belongs to oxidoreductase (class 1).  Subsequent digits represent subclasses and sub-subclasses. 

Figure 2-E-1.  Three major regulatory chemical reactions.  (a) Acetylation - addition of an acetyl group to lysine's R group by acetyltransferase.  (b) Methylation - addition of a methyl group to DNA's base (e.g. cytosine) by methylase.  (c) Phosphorylation - addition of a phosphate group to the R group of tyrosine, serine or threonine (only tyrosine is shown here) by protein kinase.

Figure 2-E-2. The role of rotamase and protein disulfide isomerase (PDI). The reactions catalyzed by the two enzymes can assist a peptide chain to fold into a correct three-dimensional structure.