The Enzyme Database FAQ

Enzyme Classification

1. How do I submit details of a new enzyme?

Fill in the New Form available at http://www.enzyme-database.org/newform.php. Provide as much detail as you can as this helps when drafting the entry.

2. What do I do if I have found an error in an enzyme entry or know of more recent publications that provide new information about an enzyme?

Fill in the Error/Update form at http://www.enzyme-database.org/updateform.php.

3. What happens once I have submitted the form?

You will receive an e-mail acknowledging receipt of your form and giving an approximate timescale for the draft entry to be at the stage where it is ready for public review. If any problems emerge while the entry is being drafted, we will write to you to ask for help/clarification or to give a reason why the enzyme cannot be included in the Enzyme List. If there are no such problems, you will receive another e-mail when the enzyme starts the public-review process, at which time, you will be asked to review the entry and provide feedback/suggestions for improvement. The time for the drafting and internal-review process is usually 4-6 weeks and the public-review period is 4 weeks.

4. How are enzymes classified?

Enzymes are classified based on the reactions they catalyse. There must be published chemical/biochemical evidence that a particular enzyme is responsible for a particular reaction before classification can be considered. Amino-acid sequence data or the fact that a gap exists in a biochemical pathway are not, in themselves, sufficient for classification purposes.

Before assigning an EC number to a new enzyme, we must first establish that it catalyses a reaction that has not been classified previously. This is easier to determine if the substrate specificity of the enzyme is high, i.e. if the enzyme uses only one compound (or a small number of compounds) as the substrate. Many enzymes have broad substrate specificity, which means that they can use many substrates to give many products, e.g. EC 1.1.1.1, alcohol dehydrogenase. In order to assign a new EC number to an alcohol dehydrogenase, there would need to be published evidence that the substrate(s) that the new enzyme uses differ(s) in some significant way from the substrate specificities of alcohol dehydrogenases already present in the Enzyme List. The same enzyme from different species does not receive a separate EC number.

Rules for the classification and nomenclature of enzymes are available here.

In straightforward cases, an enzyme entry is drafted based on the data submitted in the form (and a review of the literature) and is then sent to other members of the IUBMB Nomenclature Committee (NC-IUBMB) to be checked. If queries arise that cannot be answered by NC-IUBMB members, then other experts will be consulted [e.g. authors of paper(s) on the enzyme, experts in the specific area under consideration or the person who submitted the data].

Once the draft entry has undergone this internal-review process, the entry is made available for public review at http://www.enzyme-database.org/newenz.php and at https://www.qmul.ac.uk/sbcs/iubmb/enzyme/newenz.html for a period of 4 weeks. During the public-review process, the EC number should not be cited in publications, as the EC number occasionally changes at this stage or the entry may be withdrawn. After this time, the entry is made official and is transferred to the Enzyme List.

5. Why are enzyme names changed?

Enzyme entries contain three fields for names. The first of these is now called the Accepted name but was originally called the Recommended name and was known as the Common name between 2001 and May 2006. The other fields for names are the Other name(s) field, which lists synonyms by which an enzyme is known and the Systematic name field, which provides a more chemically explicit name for the enzyme and is usually based on the chemical names used in the reaction field. This question relates to what is now called the Accepted name. The only reason that an enzyme name will be changed is if it is incorrect or misleading. Between 2001 and 2006, the names of some enzymes were changed because the name that had been Recommended was not a name that was in common usage (e.g. could not be found using a PubMed search) so the name was replaced with the name commonly cited for the enzyme. A case where a name change resulted from a name being misleading or incorrect is that of EC 2.3.1.12, which used to be called dihydrolipoamide S-acetyltransferase but was renamed dihydrolipoyllysine-residue acetyltransferase. It is now known that the natural substrate of the enzyme is the dihydrolipoyllysine-residue, and not dihydrolipoamide, which is the reason for this change.

6. What reaction is classified?

When classifying an enzyme, the overall reaction is taken into account and not intermediate products, if they are not released from the active site.

7. What happens if there are lots of reactions associated with a single enzyme?

There are two main cases where multiple reactions are associated with a single enzyme. The first is where several different substrates can be used, leading to different products. These are called alternative reactions. The second is where consecutive reactions are catalysed by the same enzyme, i.e. the product of the first reaction becomes the substrate for the second reaction etc. For alternative reactions, a number of these may be listed in the reaction field and they will be numbered (1), (2), etc. The systematic name will be based on the first of these listed reactions. For consecutive reactions, the overall reaction catalysed is listed first, followed by the individual steps that form the overall reaction, using the numbering system (1a), (1b) etc. to indicate that they are part of the same overall reaction.

8. What is the procedure for error/update reports?

If the changes to the entry do not require complete redrafting of the enzyme entry, then the changes are usually implemented as soon as possible (after the internal-review process) and the entry does not undergo a public-review period.

9. Why is a reaction written in one direction even if the opposite direction is the one observed in vivo?

All reactions within a given sub-subclass are written in the same direction irrespective of the direction in which the reaction normally occurs in vitro/vivo. Many factors can influence the direction in which a reaction occurs so, by using the same direction for all reactions within a sub-subclass, we are not making any assumptions about the equilibrium of the reaction or its direction in vivo.

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