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Understand EC numbers in 5 minutes Part I: How EC numbers work

As a biologist you will no doubt have seen Enzyme Commission (EC) numbers. An EC number is group of four numbers separated by periods in papers discussing enzymes…something like this: EC 1.1.2.1.

But do you know what these numbers mean? Or where they came from? Or why we use them?

If not, I will aim to fix that over two articles which should take no more than 5 minutes each to read and digest. In this article I will describe how EC numbers work, and in the next article I’ll run through the history of EC numbers. Then you’ll be totally up to speed.

What EC numbers do

EC numbers (and recommended enzyme names, which I will talk about in a moment) are assigned by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology.

More than half a century ago, many new enzymes were being discovered. And scientists took great pleasure in choosing cool names for their new discoveries. But everyone was using different naming conventions so enzymology was in in danger of becoming swamped with in a myriad of names and synonyms that no-one could keep track of.

The field was in desperate need of a rational classification system. And so the EC codes and enzyme naming rules were developed.

The convention used for EC numbers

The EC numerical nomenclature classifies enzymes based on the overall reaction catalyzed: it does not identify individual enzymes but rather classes of enzymes catalyzing similar reactions.

Besides giving very specific information about the general reaction type, mechanism, substrates, products and cofactors, the EC number prevents the confusion that would otherwise result if only enzyme “common” names were used in the literature.

Since most enzymes have more than one (and often many) common names, the use of EC numbers and/or EC-approved names allows us to know exactly which enzyme is actually being referred to.

What exactly does an EC number designate?

The first digit of the EC classification code denotes the general type of reaction catalyzed by the enzyme and ranges from one to six (see Table 1).

The series of three numbers that follow this further define and narrow the details of the reaction type.  The second and third numbers are the enzyme’s sub-class and sub-sub-class, respectively, and describe the reaction with respect to the compound, group, bond or product involved in the reaction.

The final number, or serial identifier, zeros in on specific metabolites and cofactors involved [3].

For example, all type II restriction enzymes (like those used in cloning) have the code EC 3.1.21.4, which breaks down as follows:

3, denotes a hydrolase (see Table 1).

1, indicates that it acts on ester bonds

21 tells us it is a endodeoxyribonuclease producing 5′-phosphomonoesters.

4 shows that it’s a Type II site-specific deoxyribonuclease.

Table 1.  Reaction classes used in the EC nomenclature system.

Reaction Class Name Reaction catalyzed
1 Oxidoreductases Redox (oxidation/reduction) reactions
2 Transferases Transfer of a chemical group from one molecule to another
3 Hydrolases Hydrolysis: cleavage of a bond by insertion of water
4 Lyases Removal of a group with concomitant formation of a double bond, or addition of a group to a double bond
5 Isomerases Isomerization of molecules (e.g., racemases and epimerases)
6 Ligases Joining of two molecules

 

But people want names – not numbers

People are not computers, so simply naming enzymes as a bunch of numbers would not work very well. We like to label things with words. So a second task of the Enzyme Commission was to establish rules by which enzymes would be named.

The system they set up gives each enzyme a “recommended name” and a “systematic name”.

Recommended names for enzymes

The recommended name for an enzyme is normally the one that is in  common, everyday use. (In days gone by this was called the “trivial name”.) Recommended names are usually formed by adding the suffix “-ase” to the name of the enzyme’s substrate or a phrase describing it’s catalytic action.

For example, urease (EC 3.5.1.5) catalyzes the hydrolysis of urea, while alcohol dehydrogenase (EC 1.1.1.1) oxidizes alcohols to their corresponding aldehydes.

Systematic names for enzymes

An enzymes systematic name is used to prevent ambiguity. It is composed of the name of substate(s) followed by a word ending in “-ase” that specifies the type of reaction catalyzed.

For example, Malate dehydrogenase (EC 1.1.1.37) interconverts L-malate and oxaloacetate using nicotinamide adenine dinucleotide (NAD+) as a coenzyme.  It’s systematic name “L-malate: NAD+ oxidoreductase”, provides a brief chemical description of the reaction it catalyzes. It’s not as catchy as the receommended name, but it leaves you in do doubt about which enzyme you are talking about.

Which enzyme identifiers to use, and when to use them 

So, just to recap, each enzyme has three identifiers: an EC number, a recommended name, and a systematic name.

In publications dealing with enzyme studies, many (but not all) journals require that authors provide the trivial name and EC number for the enzymes being considered.  This helps to avoid needless ambiguity caused by enzyme naming differences and helps all of us stay on the same page, enzymatically speaking.

For more information on EC numbers, check out the Enzyme Nomenclature Committee website. It contains an astounding amount of information, giving a breakdown of the EC codes and information on every enzyme classified therein . It also gives a historical introduction to the EC system – and I will talk about that in the next part of this series.

References (both parts of this series)

1.  Dixon, M. and Webb, E. C. 1958. Enzymes. Academic Press, 782 p.

2.  Kohler, R. 1971. The background to Eduard Buchner’s discovery of cell-free fermentation. J. Hist. Biol. 4:35-61.

3.  Moore, J. T. and R. H. Langley. 2011. Biochemistry for Dummies.  Wiley Publishing Inc., Indianapolis, In., 340 p.

4.  Tipton, K. and S. Boyce. 2000. History of the enzyme nomenclature system. Bioinformatics 16:34-40.

2 Comments

  1. Tanya Pienaar on May 16, 2017 at 10:10 am

    I really enjoyed reading this and the simplicity in the explanation. Thank you

  2. Kurt Lager on July 9, 2013 at 5:21 am

    There are a few algorithms to predict EC numbers for unknown sequences. CatFam, Ezypred and EFICAz are among the better ones, and they are a lot better then simply Blasting KEGG.

    Besides EC numbers, there are now also, in the same style, TC numbers for classification of transporters in to different classes of transporters.

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