6.2: Enzyme Commission Number
Introduction
Enzymes are biological catalysts that speed up chemical reactions in living organisms. Scientists needed a way to organize the growing list of enzymes, leading to the creation of the Enzyme Commission (EC) number system . This system works like the Dewey Decimal System or the Library of Congress classification , but for enzymes. Each enzyme is assigned a unique four-part EC number based on the type of reaction it catalyzes.
The system, developed by the International Union of Biochemistry and Molecular Biology (IUBMB) , provides a standardized way to classify and study enzymes.
The Seven Major Classes of the Enzyme Commission
| EC Number | Class Name | Reaction Catalyzed | Example Reaction | Enzyme Examples (Trivial Names) | Enzyme Count (as of March 2025) |
|---|---|---|---|---|---|
| EC 1 | Oxidoreductases | Catalyze oxidation-reduction (redox) reactions by transferring electrons or hydrogen atoms. |
\( \text{AH} + \text{B} \rightarrow \text{A} + \text{BH} \) (reduced)
\( 2\text{A} + \text{O}_2 \rightarrow 2\text{AO} \) (oxidized) |
dehydrogenase, oxidase | 2,010 |
| EC 2 | Transferases | Transfer functional groups (methyl, acyl, amino, phosphate, etc.) between molecules. | \( \text{AB} + \text{C} \rightarrow \text{A} + \text{BC} \) | transaminase, kinase | 2,069 |
| EC 3 | Hydrolases | Break chemical bonds by adding water (hydrolysis). | \( \text{AB} + \text{H}_2\text{O} \rightarrow \text{AOH} + \text{BH} \) | lipase, amylase, peptidase, phosphatase | 1,357 |
| EC 4 | Lyases | Break bonds without hydrolysis or oxidation, often forming double bonds. |
\( \text{X-A} + \text{B-Y} \rightarrow \text{A=B} + \text{X-Y} \) |
decarboxylase | 773 |
| EC 5 | Isomerases | Rearrange atoms within a molecule without changing its molecular formula. | \( \text{ABC} \rightarrow \text{BCA} \) | isomerase, mutase | 320 |
| EC 6 | Ligases | Join two molecules by forming new bonds (C-O, C-S, C-N, or C-C) with ATP hydrolysis. | \( \text{X} + \text{Y} + \text{ATP} \rightarrow \text{XY} + \text{ADP} + \text{P}_i \) | synthetase | 249 |
| EC 7 | Translocases | Move ions or molecules across membranes. | — | transporter | 98 |
The Six Major Classes of Enzyme Reactions
EC 1: Oxidoreductases
Oxidoreductases catalyze oxidation-reduction ( redox ) reactions by transferring electrons or hydrogen atoms from one molecule to another. In these reactions, at least one substrate is oxidized while another is reduced. These enzymes are crucial in metabolic pathways such as cellular respiration.
Common oxidoreductases include dehydrogenases, reductases, and oxidases . A well-known example is lactate dehydrogenase , which plays a key role in glycolysis by converting pyruvate into lactate.
Example Reaction: Lactate Dehydrogenase
Pyruvate is reduced to lactate while NADH is oxidized to NAD⁺:
\[ \text{Pyruvate} + \text{NADH} + H^+ \rightleftharpoons \text{Lactate} + \text{NAD}^+ \]
EC 2: Transferases
Transferases move functional groups, such as methyl, acyl, amino, or phosphate groups, from one molecule to another. These enzymes often require cofactors that act as donors.
One important subclass of transferases is the kinases , which transfer phosphate groups. For example, hexokinase phosphorylates glucose, enabling it to enter metabolic pathways like glycolysis.
Example Reaction: Hexokinase
Glucose is phosphorylated using ATP:
\[ \text{Glucose} + \text{ATP} \rightarrow \text{Glucose-6-phosphate} + \text{ADP} \]
EC 3: Hydrolases
Hydrolases break chemical bonds by adding water in a process called hydrolysis . They typically act on C-O, C-N, and C-S bonds, breaking down larger molecules into smaller components.
Hydrolases are widely involved in digestion and metabolism. A key example is trypsin , a proteolytic enzyme that breaks down proteins in the digestive system.
Example Reaction: Dipeptide Hydrolysis
Alanine dipeptide hydrolysis into two alanine molecules:
\[ \text{Ala-Ala} + H_2O \rightarrow \text{Ala} + \text{Ala} \]
EC 4: Lyases
Lyases catalyze the removal or addition of functional groups to form or break double bonds, without using hydrolysis or oxidation. These enzymes can break bonds such as C=C, C=O, C=N, and C=S.
An example of a lyase is aldolase , which is essential in glycolysis for breaking down fructose-1,6-bisphosphate into smaller sugar molecules.
Example Reaction: Aldolase
Cleavage of fructose-1,6-bisphosphate into two three-carbon sugars:
\[ \text{Fructose-1,6-bisphosphate} \rightarrow \text{Glyceraldehyde-3-phosphate} + \text{Dihydroxyacetone phosphate} \]
EC 5: Isomerases
Isomerases rearrange atoms within a molecule to form an isomer. The chemical formula remains unchanged, but the structure is altered, allowing for different biochemical functions.
A common example is glucose-6-phosphate isomerase , which converts glucose-6-phosphate into fructose-6-phosphate in the second step of glycolysis.
Example Reaction: Glucose-6-Phosphate Isomerase
Conversion of glucose-6-phosphate to fructose-6-phosphate:
\[ \text{Glucose-6-phosphate} \rightleftharpoons \text{Fructose-6-phosphate} \]
EC 6: Ligases
Ligases catalyze the joining of two molecules by forming new chemical bonds, often powered by ATP hydrolysis. They are responsible for the formation of carbon-carbon, carbon-nitrogen, carbon-oxygen, and carbon-sulfur bonds.
An essential ligase is DNA ligase , which is crucial in DNA replication and repair, joining broken DNA strands together.
Example Reaction: Pyruvate Carboxylase
Formation of oxaloacetate from pyruvate:
\[ \text{Pyruvate} + \text{CO}_2 + \text{ATP} \rightarrow \text{Oxaloacetate} + \text{ADP} + \text{P}_i \]
EC 7: Translocases – An Extension to the System
In 2018, the Enzyme Commission introduced EC 7: Translocases, a new category for enzymes that facilitate the movement of molecules, ions, or macromolecules across membranes or within cellular compartments. Unlike other enzyme classes, translocases do not chemically modify their substrates. Instead, they catalyze translocation, often utilizing energy sources like ATP hydrolysis or ion gradients to drive transport.
The classification of translocases follows the general principles of enzyme nomenclature set by the Enzyme Commission:
- Only single catalytic entities should be classified as enzymes. Multi-enzyme systems that participate in transport should include “system” in their names (e.g., proton pump system).
- Translocases should not be confused with enzymes that modify their substrates. Unlike oxidoreductases (EC 1) or transferases (EC 2), translocases move substances without altering their chemical structure.
- Systematic names should reflect the molecule transported and the driving energy source. Examples include ATP-driven ion pumps and symporters using electrochemical gradients.
As research progresses, new translocases continue to be discovered and classified. Major enzyme databases, including Expasy , now recognize EC 7 translocases as an established extension to enzyme classification.
Understanding the EC Numbering System
The Enzyme Commission (EC) numbering system organizes enzymes into a hierarchy based on the reactions they catalyze. Each enzyme is assigned a unique four-part EC number (e.g., EC 3.4.11.4 ), where each level provides more specificity. Let’s explore how this system is structured.
Four Parts of the EC Number
Each enzyme’s EC number consists of four parts, separated by periods:
| EC Number Component | Meaning | Description |
|---|---|---|
| First digit | Main enzyme class (EC X) | Indicates the broad category of reaction catalyzed (e.g., oxidation-reduction, transfer, hydrolysis). |
| Second digit | Subclass (EC X.Y) | Specifies the type of reaction within the main class, often based on the type of bond or chemical group involved. |
| Third digit | Sub-subclass (EC X.Y.Z) | Further defines the reaction mechanism or the specific type of chemical transformation. |
| Fourth digit | Enzyme identifier (EC X.Y.Z.W) | Uniquely identifies the specific enzyme that catalyzes a reaction within the given subclass. |
Let's examine the classification of a specific enzyme, EC 3.4.11.4, to see how it fits into the system:
- EC 3 - Hydrolases (enzymes that use water to break bonds)
- EC 3.4 - Hydrolases that act on peptide bonds
- EC 3.4.11 - Peptidases that cleave the first amino acid from a polypeptide
- EC 3.4.11.4 - An enzyme that removes the first amino acid from a tripeptide
Example 1: Exploring an Entire Class (EC 2 - Transferases)
Now, let’s look at an entire enzyme class, EC 2 (Transferases), which move functional groups between molecules. This class includes many subclasses, each defined by the type of group being transferred:
| EC Number | Subclass Name | Description |
|---|---|---|
| EC 2.1 | Transferring One-Carbon Groups | Transfers single-carbon units such as methyl groups |
| EC 2.2 | Transferring Aldehyde or Ketone Groups | Transfers aldehyde or ketone groups between molecules |
| EC 2.3 | Acyltransferases | Transfers acyl groups (e.g., acetyl, fatty acyl) |
| EC 2.4 | Glycosyltransferases | Transfers sugar (glycosyl) groups |
| EC 2.5 | Transferring Alkyl or Aryl Groups | Transfers alkyl or aryl groups (except methyl groups) |
| EC 2.6 | Transferring Nitrogenous Groups | Transfers amino or related nitrogen-containing groups |
| EC 2.7 | Transferring Phosphorus-Containing Groups | Transfers phosphate groups (e.g., kinases) |
| EC 2.8 | Transferring Sulfur-Containing Groups | Transfers sulfur-based functional groups |
| EC 2.9 | Transferring Selenium-Containing Groups | Transfers selenium-based functional groups |
Example 2: A Deep Dive into a Subclass (EC 6.3 - Carbon-Nitrogen Bond Formation)
Finally, let’s zoom into a specific subclass, EC 6.3 (Ligases that form carbon-nitrogen bonds). This subclass includes several enzyme sub-subclasses:
| EC Number | Sub-subclass Name | Description |
|---|---|---|
| EC 6.3.1 | Acid-Ammonia (or Amine) Ligases (Amide Synthases) | Form amide bonds using ammonia or amines |
| EC 6.3.2 | Acid-Amino-Acid Ligases (Peptide Synthases) | Form peptide bonds between amino acids |
| EC 6.3.3 | Cyclo-Ligases | Form cyclic molecules via carbon-nitrogen bonds |
| EC 6.3.4 | Other Carbon-Nitrogen Ligases | Form C-N bonds but don’t fit into other categories |
| EC 6.3.5 | Carbon-Nitrogen Ligases with Glutamine as Amido-N-Donor | Use glutamine as a nitrogen donor for C-N bond formation |
History of the EC Number System
The Road to Systematic Naming
- Early enzyme names were inconsistent, often based on the substrate or reaction type (e.g., urease, maltase).
- By the 1950s, biochemists realized the need for a standardized classification system.
- In 1956, the International Commission on Enzymes was formed, and in 1961, the first edition of the EC system was published.
Growth of the EC System Over Time
| Year | Publication |
Number of
Enzymes Classified |
|---|---|---|
| 1961 | Report of the Enzyme Commission | 712 |
| 1964 | Enzyme Nomenclature | 875 |
| 1972 | Enzyme Nomenclature | 1,770 |
| 1978 | Enzyme Nomenclature | 2,122 |
| 1984 | Enzyme Nomenclature | 2,477 |
| 1992 | Enzyme Nomenclature | 3,196 |
| 2013 | — | 5,212 |
| 2020 | — | 6,520 |
| 2023 | — | 6,754 |
| 2025 | — | 6,876 |
As research expands, new enzymes continue to be classified, with the list regularly updated by the IUBMB .
Additional Resources
For up-to-date enzyme classifications, visit:
- IUBMB Enzyme Database – Official classification list.
- Expasy Enzyme Database – Searchable enzyme database.
- The Enzyme Database – Comprehensive enzyme classification and nomenclature.
- Wikipedia - EC Number – General overview.