Nomenclature Committee of the
International Union of Biochemistry and Molecular Biology (NC-IUBMB)
Enzyme Nomenclature
1.
General principles
Because
of their close interdependence, it is convenient to deal with the
classification and nomenclature together.
The
first general principle of these 'Recommendations' is that names
purporting to be names of enzymes, especially those ending in -ase,
should be used only for single enzymes, i.e. single catalytic entities.
They should not be applied to systems containing more than one enzyme. When it
is desired to name such a system on the basis of the overall reaction catalyzed
by it, the word system should be included in the name. For example, the
system catalyzing the oxidation of succinate by molecular oxygen, consisting of
succinate dehydrogenase, cytochrome oxidase, and several intermediate carriers,
should not be named succinate oxidase, but it may be called the succinate
oxidase system. Other examples of systems consisting of several
structurally and functionally linked enzymes (and cofactors) are the pyruvate
dehydrogenase system, the similar 2-oxoglutarate dehydrogenase system,
and the fatty acid synthase system.
In
this context it is appropriate to express disapproval of a loose and misleading
practice that is found in the biological literature. It consists in designation
of a natural substance (or even of an hypothetical active principle),
responsible for a physiological or biophysical phenomenon that cannot be
described in terms of a definite chemical reaction, by the name of the
phenomenon in conjugation with the suffix -ase, which implies an
individual enzyme. Some examples of such phenomenase nomenclature, which
should be discouraged even if there are reasons to suppose that the particular
agent may have enzymic properties, are: permease, translocase, reparase,
joinase, replicase, codase, etc..
The
second general principle is that enzymes are principally classified and
named according to the reaction they catalyze. The chemical reaction catalyzed
is the specific property that distinguishes one enzyme from another, and it is
logical to use it as the basis for the classification and naming of enzymes.
Several
alternative bases for classification and naming had been considered, e.g.
chemical nature of the enzymes (whether it is a flavoprotein, a hemoprotein, a
pyridoxal-phosphate protein, a copper protein, and so on), or chemical nature
of the substrate (nucleotides, carbohydrates, proteins, etc.). The first
cannot serve as a general basis, for only a minority of enzymes has such
identifiable prosthetic groups. The chemical nature of the enzyme has, however,
been used exceptionally in certain cases where classification based on
specificity is difficult, for example, with the peptidases (subclass EC 3.4). The second basis for classification is hardly practicable,
owing to the great variety of substances acted upon and because it is not
sufficiently informative unless the type of reaction is also given. It is the
overall reaction, as expressed by the formal equation that should be taken as
the basis. Thus, the intimate mechanism of the reaction, and the formation of
intermediate complexes of the reactants with the enzyme is not taken into
account, but only the observed chemical change produced by the complete enzyme
reaction. For example, in those cases in which the enzyme contains a prosthetic
group that serves to catalyze transfer from a donor to an acceptor (e.g.
flavin, biotin, or pyridoxal-phosphate enzymes) the name of the prosthetic
group is not normally included in the name of the enzyme. Nevertheless, where
alternative names are possible, the mechanism may be taken into account in
choosing between them.
A
consequence of the adoption of the chemical reaction as the basis for naming
enzymes is that a systematic name cannot be given to an enzyme until it is known
what chemical reaction it catalyzes. This applies, for example, to a few
enzymes that have so far not been shown to catalyze any chemical reaction, but
only isotopic exchanges; the isotopic exchange gives some idea of one step in
the overall chemical reaction, but the reaction as a whole remains unknown.
A
second consequence of this concept is that a certain name designates not a
single enzyme protein but a group of proteins with the same catalytic property.
Enzymes from different sources (various bacterial, plant or animal species) are
classified as one entry. The same applies to isoenzymes (see below). However,
there are exceptions to this general rule. Some are justified because the
mechanism of the reaction or the substrate specificity is so different as to
warrant different entries in the enzyme list. This applies, for example, to the
two cholinesterases, EC 3.1.1.7 and 3.1.1.8, the two citrate hydro-lyases, EC
4.2.1.3 and 4.2.1.4, and the two amine oxidases, EC 1.4.3.4 and 1.4.3.6. Others
are mainly historical, e.g. acid and alkaline phosphatases (EC 3.1.3.1
and EC 3.1.3.2).
A
third general principle adopted is that the enzymes are divided into
groups on the basis of the type of reaction catalyzed, and this, together with
the name(s) of the substrate(s) provides a basis for naming individual enzymes.
It is also the basis for classification and code numbers.
Special
problems attend the classification and naming of enzymes catalyzing complicated
transformations that can be resolved into several sequential or coupled
intermediary reactions of different types, all catalyzed by a single enzyme
(not an enzyme system). Some of the steps may be spontaneous non-catalytic
reactions, while one or more intermediate steps depend on catalysis by the
enzyme. Wherever the nature and sequence of intermediary reactions is known or
can be presumed with confidence, classification and naming of the enzyme should
be based on the first enzyme-catalyzed step that is essential to the subsequent
transformations, which can be indicated by a supplementary term in parentheses,
e.g. acetyl-CoA:glyoxylate C-acetyltransferase (thioester-hydrolysing,
carboxymethyl-forming) (EC 2.3.3.9, cf. section 3).
To
classify an enzyme according to the type of reaction catalyzed, it is occasionally
necessary to choose between alternative ways of regarding a given reaction.
Some considerations of this type are outlined in section 3 of this chapter. In
general, that alternative should be selected which fits in best with the
general system of classification and reduces the number of exceptions.
One
important extension of this principle is the question of the direction in which
the reaction is written for the purposes of classification. To simplify the
classification, the direction chosen should be the same for all enzymes in a
given class, even if this direction has not been demonstrated for all. Thus the
systematic names, on which the classification and code numbers are
based, may be derived from a written reaction, even though only the reverse of this
has been actually demonstrated experimentally. In the list in this volume, the
reaction is written to illustrate the classification, i.e. in the
direction described by the systematic name. However, the common name may
be based on either direction of reaction, and is often based on the presumed
physiological direction.
Many
examples of this usage are found in section 1 of the list. The reaction for EC
1.1.1.9 is written as an oxidation of xylitol by NAD+, in
parallel with all other oxidoreductases in subgroup EC 1.1.1, and the
systematic name is accordingly, xylitol:NAD+
2-oxidoreductase (D-xylulose-forming).
However, the common name, based on the reverse direction of reaction, is D-xylulose reductase.
2.
Common and Systematic Names
The
first Enzyme Commission gave much thought to the question of a systematic and
logical nomenclature for enzymes, and finally recommended that there should be
two nomenclatures for enzymes, one systematic, and one working or trivial. The
systematic name of an enzyme, formed in accordance with definite rules, showed
the action of an enzyme as exactly as possible, thus identifying the enzyme
precisely. The trivial name was sufficiently short for general use, but not
necessarily very systematic; in a great many cases it was a name already in
current use. The introduction of (often cumbersome) systematic names was
strongly criticized. In many cases the reaction catalyzed is not much longer
than the systematic name and can serve just as well for identification,
especially in conjunction with the code number.
The
Commission for Revision of Enzyme Nomenclature discussed this problem at
length, and a change in emphasis was made. It was decided to give the trivial
names more prominence in the Enzyme List; they now follow immediately after the
code number, and are described as Common Name. Also, in the index the common
names are indicated by an asterisk. Nevertheless, it was decided to retain the
systematic names as the basis for classification for the following reasons:
(i)
The code number alone is only useful for identification of an enzyme when a
copy of the Enzyme List is at hand, whereas the systematic name is
self-explanatory;
(ii)
The systematic name stresses the type of reaction; the reaction equation does not;
(iii)
Systematic names can be formed for new enzymes by the discoverer, by
application of the rules, but code numbers should not be assigned by
individuals;
(iv)
Common names for new enzymes are frequently formed as a condensed version of
the systematic name; therefore, the systematic names are helpful in finding
common names that are in accordance with the general pattern.
It
is recommended that for enzymes that are not the main subject of a paper or
abstract, the common names should be used, but they should be identified at
their first mention by their code numbers and source. Where an enzyme is the
main subject of a paper or abstract, its code number, systematic name, or,
alternatively, the reaction equation and source should be given at its first
mention; thereafter the common name should be used. In the light of the fact
that enzyme names and code numbers refer to reactions catalyzed rather than to
discrete proteins, it is of special importance to give also the source of the
enzyme for full identification; in cases where multiple forms are known to
exist, knowledge of this should be included where available.
When
a paper deals with an enzyme that is not yet in the Enzyme List, the author may
introduce a new name and, if desired, a new systematic name, both formed
according to the recommended rules. A number should be assigned only by the
Nomenclature Committee of IUBMB.
The
Enzyme List contains one or more references for each enzyme. It should be
stressed that no attempt has been made to provide a complete bibliography, or
to refer to the first description of an enzyme. The references are intended to
provide sufficient evidence for the existence of an enzyme catalyzing the
reaction as set out. Where there is a major paper describing the purification
and specificity of an enzyme, or a major review article, this has been quoted
to the exclusion of earlier and later papers. In some cases separate references
are given for animal, plant and bacterial enzymes.
3.
Scheme for the classification of enzymes and the generation of EC numbers
The
first Enzyme Commission, in its report in 1961, devised a system for
classification of enzymes that also serves as a basis for assigning code
numbers to them. These code numbers, prefixed by EC, which are now widely in
use, contain four elements separated by points, with the following meaning:
(i)
The first number shows to which of the six main divisions (classes) the enzyme
belongs,
(ii)
The second figure indicates the subclass,
(iii)
The third figure gives the sub-subclass,
(iv)
The fourth figure is the serial number of the enzyme in its sub-subclass.
The
subclasses and sub-subclasses are formed according to principles indicated
below.
The
main divisions and subclasses are:
No.
|
Class
|
Type of reaction
catalyzed
|
1
|
Oxidoreductases
|
Transfer
of electrons (hydride ions or H atoms)
|
2
|
Transferases
|
Group
transfer reactions
|
3
|
Hydrolases
|
Hydrolysis
reactions (transfer of functional groups to water)
|
4
|
Lyases
|
Addition
of groups to double bonds, or formation of double bonds by removal of groups
|
5
|
Isomerases
|
Transfer
of groups within molecules to yield isomeric forms
|
6
|
Ligases
|
Formation
of C-C, C-S, C-O, and C-N bonds
by condensation reactions coupled to ATP cleavage
|
Class
1. Oxidoreductases.
To
this class belong all enzymes catalyzing oxidoreduction reactions. The
substrate that is oxidized is regarded as hydrogen donor. The systematic name
is based on donor:acceptor oxidoreductase. The common name will be dehydrogenase,
wherever this is possible; as an alternative, reductase can be used. Oxidase
is only used in cases where O2 is the acceptor.
The
second figure in the code number of the oxidoreductases, unless it is 11, 13,
14 or 15, indicates the group in the hydrogen (or electron) donor that
undergoes oxidation: 1 denotes a -CHOH- group, 2 a -CHO or -CO-COOH group or
carbon monoxide, and so on, as listed in the key.
The
third figure, except in subclasses EC 1.11, EC 1.13, EC 1.14 and EC 1.15,
indicates the type of acceptor involved: 1 denotes NAD(P)+, 2 a
cytochrome, 3 molecular oxygen, 4 a disulfide, 5 a quinone or similar compound,
6 a nitrogenous group, 7 an iron-sulfur protein and 8 a flavin. In subclasses
EC 1.13 and EC 1.14 a different classification scheme is used and
sub-subclasses are numbered from 11 onwards.
It
should be noted that in reactions with a nicotinamide coenzyme this is always
regarded as acceptor, even if this direction of the reaction is not readily
demonstrated. The only exception is the subclass EC 1.6, in which NAD(P)H is
the donor; some other redox catalyst is the acceptor.
Although
not used as a criterion for classification, the two hydrogen atoms at carbon-4
of the dihydropyridine ring of nicotinamide nucleotides are not equivalent in
that the hydrogen is transferred stereospecifically.
Class
2. Transferases.
Transferases
are enzymes transferring a group, e.g. a methyl group or a glycosyl
group, from one compound (generally regarded as donor) to another compound
(generally regarded as acceptor). The systematic names are formed according to
the scheme donor:acceptor grouptransferase. The common names are
normally formed according to acceptor grouptransferase or donor
grouptransferase. In many cases, the donor is a cofactor (coenzyme) charged
with the group to be transferred. A special case is that of the transaminases
(see below).
Some
transferase reactions can be viewed in different ways. For example, the enzyme-catalyzed
reaction
X-Y + Z = X + Z-Y
may
be regarded either as a transfer of the group Y from X to Z, or as a breaking
of the X-Y bond by the introduction of Z. Where Z represents phosphate or
arsenate, the process is often spoken of as 'phosphorolysis' or 'arsenolysis',
respectively, and a number of enzyme names based on the pattern of phosphorylase
have come into use. These names are not suitable for a systematic nomenclature,
because there is no reason to single out these particular enzymes from the
other transferases, and it is better to regard them simply as Y-transferases.
In
the above reaction, the group transferred is usually exchanged, at least
formally, for hydrogen, so that the equation could more strictly be written as:
X-Y + Z-H = X-H + Z-Y.
Another
problem is posed in enzyme-catalyzed transaminations, where the -NH2 group and
-H are transferred to a compound containing a carbonyl group in exchange for
the =O of that group, according to the general equation:
R1-CH(-NH2)-R2 + R3-CO-R4 ![[arrow right]](file:///C:/DOCUME%7E1/UP/LOCALS%7E1/Temp/msohtmlclip1/01/clip_image001.gif)
R1-CO-R2 + R3-CH(-NH2)-R4.
R1-CO-R2 + R3-CH(-NH2)-R4.
The
reaction can be considered formally as oxidative deamination of the donor (e.g.
amino acid) linked with reductive amination of the acceptor (e.g. oxo
acid), and the transaminating enzymes (pyridoxal-phosphate proteins) might be
classified as oxidoreductases. However, the unique distinctive feature of the
reaction is the transfer of the amino group (by a well-established mechanism
involving covalent substrate-coenzyme intermediates), which justified
allocation of these enzymes among the transferases as a special subclass (EC
2.6.1, transaminases).
The
second figure in the code number of transferases indicates the group
transferred; a one-carbon group in EC 2.1, an aldehydic or ketonic group in EC
2.2, an acyl group in EC 2.3 and so on.
The
third figure gives further information on the group transferred; e.g.
subclass EC 2.1 is subdivided into methyltransferases (EC 2.1.1), hydroxymethyl-
and formyltransferases (EC 2.1.2) and so on; only in subclass EC 2.7,
does the third figure indicate the nature of the acceptor group.
Class
3. Hydrolases.
These
enzymes catalyze the hydrolytic cleavage of C-O, C-N, C-C and some other bonds,
including phosphoric anhydride bonds. Although the systematic name always
includes hydrolase, the common name is, in many cases, formed by the
name of the substrate with the suffix -ase. It is understood that the
name of the substrate with this suffix means a hydrolytic enzyme.
A
number of hydrolases acting on ester, glycosyl, peptide, amide or other bonds
are known to catalyze not only hydrolytic removal of a particular group from
their substrates, but likewise the transfer of this group to suitable acceptor
molecules. In principle, all hydrolytic enzymes might be classified as
transferases, since hydrolysis itself can be regarded as transfer of a specific
group to water as the acceptor. Yet, in most cases, the reaction with water as
the acceptor was discovered earlier and is considered as the main physiological
function of the enzyme. This is why such enzymes are classified as hydrolases
rather than as transferases.
Some
hydrolases (especially some of the esterases and glycosidases) pose problems
because they have a very wide specificity and it is not easy to decide if two
preparations described by different authors (perhaps from different sources)
have the same catalytic properties, or if they should be listed under separate
entries. An example is vitamin A esterase (formerly EC 3.1.1.12, now
believed to be identical with EC 3.1.1.1). To some extent the choice must be
arbitrary; however, separate entries should be given only when the
specificities are sufficiently different.
Another
problem is that proteinases have 'esterolytic' action; they usually hydrolyse
ester bonds in appropriate substrates even more rapidly than natural peptide
bonds. In this case, classification among the peptide hydrolases is based on
historical priority and presumed physiological function.
The
second figure in the code number of the hydrolases indicates the nature of the
bond hydrolysed; EC 3.1 are the esterases; EC 3.2 the glycosylases,
and so on.
The
third figure normally specifies the nature of the substrate, e.g. in the
esterases the carboxylic ester hydrolases (EC 3.1.1), thiolester
hydrolases (EC 3.1.2), phosphoric monoester hydrolases (EC 3.1.3);
in the glycosylases the O-glycosidases (EC 3.2.1), N-glycosylases
(EC 3.2.2), etc. Exceptionally, in the case of the peptidyl-peptide
hydrolases the third figure is based on the catalytic mechanism as shown by
active centre studies or the effect of pH.
Class
4. Lyases.
Lyases
are enzymes cleaving C-C, C-O, C-N, and other bonds by elimination, leaving
double bonds or rings, or conversely adding groups to double bonds. The
systematic name is formed according to the pattern substrate group-lyase.
The hyphen is an important part of the name, and to avoid confusion should not
be omitted, e.g. hydro-lyase not 'hydrolyase'. In the common names,
expressions like decarboxylase, aldolase, dehydratase (in case of
elimination of CO2, aldehyde, or water) are used. In cases where the reverse
reaction is much more important, or the only one demonstrated, synthase
(not synthetase) may be used in the name. Various subclasses of the lyases
include pyridoxal-phosphate enzymes that catalyze the elimination of a β- or
γ-substituent from an α-amino acid followed by a replacement of this
substituent by some other group. In the overall replacement reaction, no
unsaturated end-product is formed; therefore, these enzymes might formally be
classified as alkyl-transferases (EC 2.5.1...). However, there is ample
evidence that the replacement is a two-step reaction involving the transient
formation of enzyme-bound α,β(or β,γ)-unsaturated amino acids. According to the
rule that the first reaction is indicative for classification, these enzymes
are correctly classified as lyases. Examples are tryptophan synthase
(EC 4.2.1.20) and cystathionine β-synthase (EC 4.2.1.22).
The
second figure in the code number indicates the bond broken: EC 4.1 is
carbon-carbon lyases, EC 4.2 carbon-oxygen lyases and so on.
The
third figure gives further information on the group eliminated (e.g. CO2 in EC
4.1.1, H2O in EC 4.2.1).
Class
5. Isomerases.
These
enzymes catalyze geometric or structural changes within one molecule. According
to the type of isomerism, they may be called racemases, epimerases,
cis-trans-isomerases, isomerases, tautomerases, mutases or
cycloisomerases.
In
some cases, the interconversion in the substrate is brought about by an
intramolecular oxidoreduction (EC 5.3); since hydrogen donor and acceptor are
the same molecule, and no oxidized product appears, they are not classified as
oxidoreductases, even though they may contain firmly bound NAD(P)+.
The
subclasses are formed according to the type of isomerism, the sub-subclasses to
the type of substrates.
Class
6. Ligases.
Ligases
are enzymes catalyzing the joining together of two molecules coupled with the
hydrolysis of a diphosphate bond in ATP or a similar triphosphate. The
systematic names are formed on the system X:Y ligase (ADP-forming). In
earlier editions of the list the term synthetase has been used for the
common names. Many authors have been confused by the use of the terms synthetase
(used only for Group 6) and synthase (used throughout the list when it
is desired to emphasis the synthetic nature of the reaction). Consequently
NC-IUB decided in 1983 to abandon the use of synthetase for common names, and
to replace them with names of the type X-Y ligase. In a few cases in
Group 6, where the reaction is more complex or there is a common name for the
product, a synthase name is used (e.g. EC 6.3.2.11 and EC 6.3.5.1).
It
is recommended that if the term synthetase is used by authors, it should
continue to be restricted to the ligase group.
The
second figure in the code number indicates the bond formed: EC 6.1 for C-O
bonds (enzymes acylating tRNA), EC 6.2 for C-S bonds (acyl-CoA derivatives), etc.
Sub-subclasses are only in use in the C-N ligases.
In
a few cases it is necessary to use the word other in the description of
subclasses and sub-subclasses. They have been provisionally given the figure
99, in order to leave space for new subdivisions.
From
time to time, some enzymes have been deleted from the List, while some others
have been renumbered. However, the old numbers have not been
allotted to new enzymes; rather the place has been left vacant and
cross-reference is made according to the following scheme:
[EC
1.2.3.4 Deleted entry: old name]
or
[EC
1.2.3.4 Transferred entry: now EC 5.6.7.8 - common name].
Entries
for reclassified enzymes transferred from one position in the List to another
are followed, for reference, by a comment indicating the former number.
It
is regarded as important that the same policy be followed in future revisions
and extensions of the Enzyme List, which may become necessary from time to
time.
4.
Rules for Classification and Nomenclature
(a)
General Rules for Systematic Names and Guidelines for Common Names
Rule
1.
(Common
Names)
Generally
accepted trivial names of substrates may be used in enzyme names. The prefix D- should be omitted for all D-sugars and L- for individual amino acids, unless
ambiguity would be caused. In general, it is not necessary to indicate
positions of substituents in common names, unless it is necessary to prevent
two different enzymes having the same name. The prefix keto is no longer
used for derivatives of sugars in which -CHOH- has been replaced by -CO-; they
are named throughout as dehydro-sugars.
(Systematic
Names)
To
produce usable systematic names, accepted trivial names of substrates forming
part of the enzyme names should be used. Where no accepted and convenient
trivial names exist, the official IUPAC rules of nomenclature should be applied
to the substrate name. The 1,2,3 system of locating substituents should be used
instead of the α,β,γ system, although group names such as β-aspartyl-,
γ-glutamyl-, and also β-alanine and γ-lactone are permissible; α,β should
normally be used for indicating configuration, as in α-D-glucose. For nucleotide groups, adenylyl
(not adenyl), etc. should be the form used. The name oxo acids (not keto
acids) may be used as a class name, and for individual compounds in which -CH2- has been
replaced by -CO-, oxo should be used.
Rule
2.
Where
the substrate is normally in the form of an anion, its name should end in -ate
rather than -ic; e.g. lactate dehydrogenase, not 'lactic dehydrogenase'
or 'lactic acid dehydrogenase'.
Rule
3.
Commonly
used abbreviations for substrates, e.g. ATP, may be used in names of
enzymes, but the use of new abbreviations (not listed in recommendations of the
IUPAC-IUB Commission on Biochemical Nomenclature) should be discouraged.
Chemical formulae should not normally be used instead of names of substrates.
Abbreviations for names of enzymes, e.g. GDH, should not be used.
Rule
4.
Names
of substrates composed of two nouns, such as glucose phosphate, which are
normally written with a space, should be hyphenated when they form part of the
enzyme names, and thus become adjectives, e.g. glucose-6-phosphate
1-dehydrogenase (EC 1.1.1.49). This follows standard practice in phrases
where two nouns qualify a third; see, for example, Handbook for Chemical
Society Authors, 2nd edn, p. 14 (The Chemical Society, London, 1961).
Rule
5.
The
use as enzyme names of descriptions such as condensing enzyme,
acetate-activating enzyme, pH 5 enzyme should be discontinued as soon as
the catalyzed reaction is known. The word activating should not be used
in the sense of converting the substrate into a substance that reacts further;
all enzymes act by activating their substrates, and the use of the word in this
sense may lead to confusion.
Rule
6.
(Common
Names)
If
it can be avoided, a common name should not be based on a substance that is not
a true substrate, e.g. enzyme EC 4.2.1.17 should not be called
'crotonase', since it does not act on crotonate.
Rule
7.
(Common
Names)
Where
a name in common use gives some indication of the reaction and is not incorrect
or ambiguous, its continued use is recommended. In other cases a common name is
based on the same general principles as the systematic name (see Rule 7 below)
but with a minimum of detail, to produce a name short enough for convenient
use. A few names of proteolytic enzymes ending in -in are retained; all
other enzyme names should end in -ase.
(Systematic
Names)
Systematic
names consist of two parts. The first contains the name of the substrate or, in
the case of a bimolecular reaction, of the two substrates separated by a colon.
The second part, ending in -ase, indicates the nature of the reaction.
Rule
8.
A
number of generic words indicating a type of reaction may be used in either
common or systematic names: oxidoreductase, oxygenase, transferase (with
a prefix indicating the nature of the group transferred), hydrolase, lyase,
racemase, epimerase, isomerase, mutase, ligase.
Rule
9.
(Common
Names)
A
number of additional generic words indicating reaction types are used in common
names, but not in the systematic nomenclature, e.g. dehydrogenase,
reductase, oxidase, peroxidase, kinase, tautomerase, deaminase, dehydratase,
etc..
Rule
10.
Where
additional information is needed to make the reaction clear, a phrase
indicating the reaction or a product should be added in parentheses after the
second part of the name e.g. (ADP-forming), (dimerizing), (CoA-acylating).
Rule
11.
(Common
Names)
The
direct attachment of -ase to the name of the substrate will indicate
that the enzyme brings about hydrolysis.
(Systematic
Names)
The
suffix -ase should never be attached directly to the name of the
substrate.
Rule
12.
(Common
Names)
The
name 'dehydrase' which was at one time used for both dehydrogenating and
dehydrating enzymes, should not be used. Dehydrogenase will be used for
the former and dehydratase for the latter.
Rule
13.
(Common
Names)
Where
possible, common names should normally be based on a reaction direction that
has been demonstrated, e.g. dehydrogenase or reductase, decarboxylase
or carboxylase.
(Systematic
Names)
In
the case of reversible reactions, the direction chosen for naming should be the
same for all the enzymes in a given class, even if this direction has not been
demonstrated for all. Thus, systematic names may be based on a written
reaction, even though only the reverse of this has been actually demonstrated
experimentally.
Rule
14.
(Systematic
Names)
When
the overall reaction includes two different changes, e.g. an oxidative
demethylation, the classification and systematic name should be based, whenever
possible, on the one (or the first one) catalyzed by the enzyme; the other
function(s) should be indicated by adding a suitable participle in parentheses,
as in the case of sarcosine:oxygen oxidoreductase (demethylating) (EC
1.5.3.1); D-aspartate:oxygen
oxidoreductase (deaminating) (EC 1.4.3.1); L-serine hydro-lyase (adding indoleglycerol-phosphate)
(EC 4.2.1.20).
Other
examples of such additions are (decarboxylating), (cyclizing),
(acceptor-acylating), (isomerizing).
Rule
15.
When
an enzyme catalyzes more than one type of reaction, the name should normally
refer to one reaction only. Each case must be considered on its merits, and the
choice must be, to some extent, arbitrary. Other important activities of the
enzyme may be indicated in the List under 'Reaction' or 'Comments'.
Similarly,
when any enzyme acts on more than one substrate (or pair of substrates), the
name should normally refer only to one substrate (or pair of substrates),
although in certain cases it may be possible to use a term that covers a whole
group of substrates, or an alternative substrate may be given in parentheses.
Rule
16.
A
group of enzymes with closely similar specificities should normally be
described by a single entry. However, when the specificity of two enzymes catalyzing
the same reactions is sufficiently different (the degree of difference being a
matter of arbitrary choice) two separate entries may be made, e.g. EC
1.2.1.4 and EC 1.2.1.7. Separate entries are also appropriate for enzymes
having similar catalytic functions, but known to differ basically with regard
to reaction mechanism or to the nature of the catalytic groups, e.g. amine
oxidase (flavin-containing) (EC 1.4.3.4) and amine oxidase
(copper-containing) (EC 1.4.3.6).
(b)
Rules and Guidelines for Particular Classes of Enzymes
Class
1
Rule
17.
(Common
Names)
The
terms dehydrogenase or reductase will be used much as hitherto.
The latter term is appropriate when hydrogen transfer from the substance
mentioned as donor in the systematic name is not readily demonstrated. Transhydrogenase
may be retained for a few well-established cases. Oxidase is used only
for cases there O2 acts as an acceptor, and oxygenase only for those
cases where the O2 molecule (or part of it) is directly incorporated into the
substrate. Peroxidase is used for enzymes using H2O2 as
acceptor. Catalase must be regarded as exceptional. Where no ambiguity
is caused, the second reactant is not usually named; but where required to
prevent ambiguity, it may be given in parentheses, e.g. EC 1.1.1.1, alcohol
dehydrogenase and EC 1.1.1.2, alcohol dehydrogenase (NADP+).
(Systematic
Names)
All
enzymes catalyzing oxidoreductions should be named oxidoreductases in
the systematic nomenclature, and the names formed on the pattern donor:acceptor
oxidoreductase.
Rule
18.
(Systematic
Names)
For
oxidoreductases using NAD+ or NADP+, the coenzyme should always be named as the acceptor except
for the special case of Section 1.6 (enzymes whose normal physiological
function is regarded as reoxidation of the reduced coenzyme). Where the enzyme
can use either coenzyme, this should be indicated by writing NAD(P)+.
Rule
19.
Where
the true acceptor is unknown and the oxidoreductase has only been shown to
react with artificial acceptors, the word acceptor should be written in
parentheses, as in the case of EC 1.3.99.1, succinate:(acceptor)
oxidoreductase.
Rule
20.
(Common
Names)
Oxidoreductases
that bring about the incorporation of molecular oxygen into one donor or into
either or both of a pair of donors are named oxygenase. If only one atom
of oxygen is incorporated the term monooxygenase is used; if both atoms
of O2 are incorporated, the term dioxygenase is used.
(Systematic
Names)
Oxidoreductases
bringing about the incorporation of oxygen into one of paired donors should be
named on the pattern donor,donor:oxygen oxidoreductase (hydroxylating).
Class
2.
Rule
21.
(Common
Names)
Only
one specific substrate or reaction product is generally indicated in the common
names, together with the group donated or accepted.
The
forms transaminase, etc., may be replaced if desired by the
corresponding forms aminotransferase, etc..
A
number of special words are used to indicate reaction types, e.g. kinase
to indicate a phosphate transfer from ATP to the named substrate (not
'phosphokinase'), diphosphokinase for a similar transfer of diphosphate.
(Systematic
Names)
Enzymes
catalyzing group-transfer reactions should be named transferase and the
names formed on the pattern donor:acceptor group-transferred-transferase,
e.g. ATP:acetate phosphotransferase (EC 2.7.2.1). A figure may be prefixed
to show the position to which the group is transferred, e.g. ATP:D-fructose 1-phosphotransferase (EC 2.7.1.3). The spelling 'transphorase' should not be
used. In the case of the phosphotransferases, ATP should always be named as the
donor. In the case of the transaminases involving 2-oxoglutarate, the latter
should always be named as the acceptor.
Rule
22.
(Systematic
Names)
The
prefix denoting the group transferred should, as far as possible, be
non-committal with respect to the mechanism of the transfer, e.g. phospho-,
rather than phosphate-.
Class
3.
Rule
23.
(Common
Names)
The
direct addition of -ase to the name of the substrate generally denotes a
hydrolase. Where this is difficult, e.g. for EC 3.1.2.1, the word hydrolase
may be used. Enzymes should not normally be given separate names merely on the
basis of optimal conditions for activity. The acid and alkaline phosphatases
(EC 3.1.3.1-2) should be regarded as special cases and not as examples to be
followed. The common name lysozyme is also exceptional.
(Systematic
Names)
Hydrolysing
enzymes should be systematically named on the pattern substrate hydrolase.
Where the enzyme is specific for the removal of a particular group, the group
may be named as a prefix, e.g. adenosine aminohydrolase (EC 3.5.4.4). In
a number of cases this group can also be transferred by the enzyme to other
molecules, and the hydrolysis itself might be regarded as a transfer of the
group to water.
Class
4.
Rule
24.
(Common
Names)
The
old names decarboxylase, aldolase, etc., are retained; and dehydratase
(not 'dehydrase') is used for the hydro-lyases. 'Synthetase' should not be used
for any enzymes in this class. The term synthase may be used instead for
any enzyme in this class (or any other class) when it is desired to emphasize
the synthetic aspect of the reaction.
(Systematic
Names)
Enzymes
removing groups from substrates non-hydrolytically, leaving double bonds (or
adding groups to double bonds) should be called lyases in the systematic
nomenclature. Prefixes such as hydro-, ammonia- should be used to denote
the type of reaction, e.g. (S)-malate hydro-lyase (EC 4.2.1.2).
Decarboxylases should be regarded as carboxy-lyases. A hyphen should
always be written before lyase to avoid confusion with hydrolases,
carboxylases, etc.
Rule
25.
(Common
Names)
Where
the equilibrium warrants it, or where the enzyme has long been named after a
particular substrate, the reverse reaction may be taken as the basis of the
name, using hydratase, carboxylase, etc., e.g. fumarate hydratase for EC
4.2.1.2 (in preference to 'fumarase', which suggests an enzyme hydrolysing
fumarate).
(Systematic
Names)
The
complete molecule, not either of the parts into which it is separated, should
be named as the substrate.
The
part indicated as a prefix to -lyase is the more characteristic and
usually, but not always, the smaller of the two reaction products. This may
either be the removed (saturated) fragment of the substrate molecule, as in ammonia-,
hydro-, thiol-lyases, etc. or the remaining unsaturated fragment, e.g.
in the case of carboxy-, aldehyde- or oxo-acid-lyases.
Rule
26.
Various
subclasses of the lyases include a number of strictly specific or
group-specific pyridoxal-5-phosphate enzymes that catalyze elimination
reactions of β- or γ-substituted α-amino acids. Some closely related
pyridoxal-5-phosphate-containing enzymes, e.g. tryptophan synthase (EC
4.2.1.20) and cystathionine β-synthase (EC 4.2.1.22) catalyze replacement
reactions in which a β- or γ-substituent is replaced by a second reactant
without creating a double bond. Formally, these enzymes appear to be
transferases rather than lyases. However, there is evidence that in these cases
the elimination of the β- or γ-substituent and the formation of an unsaturated
intermediate is the first step in the reaction. Thus, applying rule 14, these
enzymes are correctly classified as lyases.
Class
5.
Rule
27.
In
this class, the common names are, in general, similar to the systematic names
which indicate the basis of classification.
Rule
28.
Isomerase will be used as a general name for enzymes in this class.
The types of isomerization will be indicated in systematic names by prefixes, e.g.
maleate cis-trans-isomerase (EC 5.2.1.1), phenylpyruvate
keto-enol-isomerase (EC 5.3.2.1), 3-oxosteroid Δ5-
Δ4-isomerase
(EC 5.3.3.1). Enzymes catalyzing an aldose-ketose interconversion will be known
as aldose-ketose-isomerases, e.g. L-arabinose aldose-ketose-isomerase
(EC 5.3.1.4). When the isomerization consists of an intramolecular transfer of
a group, the enzyme is named a mutase, e.g. EC 5.4.1.1, and the phosphomutases
in sub-subclass 5.4.2; when it consists of an intramolecular lyase-type
reaction, e.g. EC 5.5.1.1, it is systematically named a lyase (decyclizing).
Rule
29.
Isomerases
catalyzing inversions at asymmetric centres should be termed racemases
or epimerases, according to whether the substrate contains one, or more
than one, centre of asymmetry: compare, for example, EC 5.1.1.5 with EC
5.1.1.7. A numerical prefix to the word epimerase should be used to show
the position of the inversion.
Class
6.
Rule
30
(Common
Names)
Common
names for enzymes of this class were previously of the type XY synthetase.
However, as this use has not always been understood and synthetase has been
confused with synthase (see Rule 24), it is now recommended that as far as
possible the common names should be similar in form to the systematic names.
(Systematic
Names)
The
class of enzymes catalyzing the linking together of two molecules, coupled with
the breaking of a diphosphate link in ATP, etc. should be known as ligases.
These enzymes were often previously known as 'synthetases'; however, this
terminology differs from all other systematic enzyme names in that it is based
on the product and not on the substrate. For these reasons, a new systematic
class name was necessary.
Rule
31
(Common
Names)
The
common names should be formed on the pattern X-Y ligase, where X-Y is
the substance formed by linking X and Y. In certain cases, where a trivial name
is commonly used for XY, a name of the type XY synthase may be
recommended (e.g. EC 6.3.2.11, carnosine synthase).
(Systematic
Names)
The
systematic names should be formed on the pattern X:Y ligase (ADP-forming),
where X and Y are the two molecules to be joined together. The phrase shown in
parentheses indicates both that ATP is the triphosphate involved, and also that
the terminal diphosphate link in broken. Thus, the reaction is X + Y + ATP =
X-Y + ADP + Pi.
Rule
32.
(Common
Names)
In
the special case where glutamine acts as an ammonia-donor, this is indicated by
adding in parentheses (glutamine-hydrolysing) to a ligase name.
(Systematic
Names)
In
this case, the name amido-ligase should be used in the systematic
nomenclature.
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