Nomenclature Committee of theInternational Union of Biochemistry and Molecular Biology (NC-IUBMB)
Becauseof their close interdependence, it is convenient to deal with theclassification and nomenclature together.
Thefirst general principle of these 'Recommendations' is that namespurporting 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 itis desired to name such a system on the basis of the overall reaction catalyzedby it, the word system should be included in the name. For example, thesystem catalyzing the oxidation of succinate by molecular oxygen, consisting ofsuccinate dehydrogenase, cytochrome oxidase, and several intermediate carriers,should not be named succinate oxidase, but it may be called the succinateoxidase system. Other examples of systems consisting of severalstructurally and functionally linked enzymes (and cofactors) are the pyruvatedehydrogenase system, the similar 2-oxoglutarate dehydrogenase system,and the fatty acid synthase system.
Inthis context it is appropriate to express disapproval of a loose and misleadingpractice that is found in the biological literature. It consists in designationof a natural substance (or even of an hypothetical active principle),responsible for a physiological or biophysical phenomenon that cannot bedescribed in terms of a definite chemical reaction, by the name of thephenomenon in conjugation with the suffix -ase, which implies anindividual enzyme. Some examples of such phenomenase nomenclature, whichshould be discouraged even if there are reasons to suppose that the particularagent may have enzymic properties, are: permease, translocase, reparase,joinase, replicase, codase, etc..
Thesecond general principle is that enzymes are principally classified andnamed according to the reaction they catalyze. The chemical reaction catalyzedis the specific property that distinguishes one enzyme from another, and it islogical to use it as the basis for the classification and naming of enzymes.
Severalalternative bases for classification and naming had been considered, e.g.chemical nature of the enzymes (whether it is a flavoprotein, a hemoprotein, apyridoxal-phosphate protein, a copper protein, and so on), or chemical natureof the substrate (nucleotides, carbohydrates, proteins, etc.). The firstcannot serve as a general basis, for only a minority of enzymes has suchidentifiable prosthetic groups. The chemical nature of the enzyme has, however,been used exceptionally in certain cases where classification based onspecificity 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 notsufficiently informative unless the type of reaction is also given. It is theoverall reaction, as expressed by the formal equation that should be taken asthe basis. Thus, the intimate mechanism of the reaction, and the formation ofintermediate complexes of the reactants with the enzyme is not taken intoaccount, but only the observed chemical change produced by the complete enzymereaction. For example, in those cases in which the enzyme contains a prostheticgroup that serves to catalyze transfer from a donor to an acceptor (e.g.flavin, biotin, or pyridoxal-phosphate enzymes) the name of the prostheticgroup is not normally included in the name of the enzyme. Nevertheless, wherealternative names are possible, the mechanism may be taken into account inchoosing between them.
Aconsequence of the adoption of the chemical reaction as the basis for namingenzymes is that a systematic name cannot be given to an enzyme until it is knownwhat chemical reaction it catalyzes. This applies, for example, to a fewenzymes that have so far not been shown to catalyze any chemical reaction, butonly isotopic exchanges; the isotopic exchange gives some idea of one step inthe overall chemical reaction, but the reaction as a whole remains unknown.
Asecond consequence of this concept is that a certain name designates not asingle enzyme protein but a group of proteins with the same catalytic property.Enzymes from different sources (various bacterial, plant or animal species) areclassified as one entry. The same applies to isoenzymes (see below). However,there are exceptions to this general rule. Some are justified because themechanism of the reaction or the substrate specificity is so different as towarrant different entries in the enzyme list. This applies, for example, to thetwo cholinesterases, EC 126.96.36.199 and 188.8.131.52, the two citrate hydro-lyases, EC184.108.40.206 and 220.127.116.11, and the two amine oxidases, EC 18.104.22.168 and 22.214.171.124. Othersare mainly historical, e.g. acid and alkaline phosphatases (EC 126.96.36.199and EC 188.8.131.52).
Athird general principle adopted is that the enzymes are divided intogroups on the basis of the type of reaction catalyzed, and this, together withthe name(s) of the substrate(s) provides a basis for naming individual enzymes.It is also the basis for classification and code numbers.
Specialproblems attend the classification and naming of enzymes catalyzing complicatedtransformations that can be resolved into several sequential or coupledintermediary reactions of different types, all catalyzed by a single enzyme(not an enzyme system). Some of the steps may be spontaneous non-catalyticreactions, while one or more intermediate steps depend on catalysis by theenzyme. Wherever the nature and sequence of intermediary reactions is known orcan be presumed with confidence, classification and naming of the enzyme shouldbe based on the first enzyme-catalyzed step that is essential to the subsequenttransformations, which can be indicated by a supplementary term in parentheses,e.g. acetyl-CoA:glyoxylate C-acetyltransferase (thioester-hydrolysing,carboxymethyl-forming) (EC 184.108.40.206, cf. section 3).
Toclassify an enzyme according to the type of reaction catalyzed, it is occasionallynecessary to choose between alternative ways of regarding a given reaction.Some considerations of this type are outlined in section 3 of this chapter. Ingeneral, that alternative should be selected which fits in best with thegeneral system of classification and reduces the number of exceptions.
Oneimportant extension of this principle is the question of the direction in whichthe reaction is written for the purposes of classification. To simplify theclassification, the direction chosen should be the same for all enzymes in agiven class, even if this direction has not been demonstrated for all. Thus thesystematic names, on which the classification and code numbers arebased, may be derived from a written reaction, even though only the reverse of thishas been actually demonstrated experimentally. In the list in this volume, thereaction is written to illustrate the classification, i.e. in thedirection described by the systematic name. However, the common name maybe based on either direction of reaction, and is often based on the presumedphysiological direction.
Manyexamples of this usage are found in section 1 of the list. The reaction for EC220.127.116.11 is written as an oxidation of xylitol by NAD+, inparallel with all other oxidoreductases in subgroup EC 1.1.1, and thesystematic 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
Thefirst Enzyme Commission gave much thought to the question of a systematic andlogical nomenclature for enzymes, and finally recommended that there should betwo nomenclatures for enzymes, one systematic, and one working or trivial. Thesystematic name of an enzyme, formed in accordance with definite rules, showedthe action of an enzyme as exactly as possible, thus identifying the enzymeprecisely. The trivial name was sufficiently short for general use, but notnecessarily very systematic; in a great many cases it was a name already incurrent use. The introduction of (often cumbersome) systematic names wasstrongly criticized. In many cases the reaction catalyzed is not much longerthan the systematic name and can serve just as well for identification,especially in conjunction with the code number.
TheCommission for Revision of Enzyme Nomenclature discussed this problem atlength, and a change in emphasis was made. It was decided to give the trivialnames more prominence in the Enzyme List; they now follow immediately after thecode number, and are described as Common Name. Also, in the index the commonnames are indicated by an asterisk. Nevertheless, it was decided to retain thesystematic names as the basis for classification for the following reasons:
(i)The code number alone is only useful for identification of an enzyme when acopy of the Enzyme List is at hand, whereas the systematic name isself-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, byapplication of the rules, but code numbers should not be assigned byindividuals;
(iv)Common names for new enzymes are frequently formed as a condensed version ofthe systematic name; therefore, the systematic names are helpful in findingcommon names that are in accordance with the general pattern.
Itis recommended that for enzymes that are not the main subject of a paper orabstract, the common names should be used, but they should be identified attheir first mention by their code numbers and source. Where an enzyme is themain subject of a paper or abstract, its code number, systematic name, or,alternatively, the reaction equation and source should be given at its firstmention; thereafter the common name should be used. In the light of the factthat enzyme names and code numbers refer to reactions catalyzed rather than todiscrete proteins, it is of special importance to give also the source of theenzyme for full identification; in cases where multiple forms are known toexist, knowledge of this should be included where available.
Whena paper deals with an enzyme that is not yet in the Enzyme List, the author mayintroduce a new name and, if desired, a new systematic name, both formedaccording to the recommended rules. A number should be assigned only by theNomenclature Committee of IUBMB.
TheEnzyme List contains one or more references for each enzyme. It should bestressed that no attempt has been made to provide a complete bibliography, orto refer to the first description of an enzyme. The references are intended toprovide sufficient evidence for the existence of an enzyme catalyzing thereaction as set out. Where there is a major paper describing the purificationand specificity of an enzyme, or a major review article, this has been quotedto the exclusion of earlier and later papers. In some cases separate referencesare given for animal, plant and bacterial enzymes.
3.Scheme for the classification of enzymes and the generation of EC numbers
Thefirst Enzyme Commission, in its report in 1961, devised a system forclassification of enzymes that also serves as a basis for assigning codenumbers to them. These code numbers, prefixed by EC, which are now widely inuse, contain four elements separated by points, with the following meaning:
(i)The first number shows to which of the six main divisions (classes) the enzymebelongs,
(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.
Thesubclasses and sub-subclasses are formed according to principles indicatedbelow.
Themain divisions and subclasses are:
Type of reaction catalyzed
Transfer of electrons (hydride ions or H atoms)
Group transfer reactions
Hydrolysis reactions (transfer of functional groups to water)
Addition of groups to double bonds, or formation of double bonds by removal of groups
Transfer of groups within molecules to yield isomeric forms
Formation of C-C, C-S, C-O, and C-N bonds by condensation reactions coupled to ATP cleavage
Tothis class belong all enzymes catalyzing oxidoreduction reactions. Thesubstrate that is oxidized is regarded as hydrogen donor. The systematic nameis based on donor:acceptor oxidoreductase. The common name will be dehydrogenase,wherever this is possible; as an alternative, reductase can be used. Oxidaseis only used in cases where O2 is the acceptor.
Thesecond 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 thatundergoes oxidation: 1 denotes a -CHOH- group, 2 a -CHO or -CO-COOH group orcarbon monoxide, and so on, as listed in the key.
Thethird 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 acytochrome, 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 subclassesEC 1.13 and EC 1.14 a different classification scheme is used andsub-subclasses are numbered from 11 onwards.
Itshould be noted that in reactions with a nicotinamide coenzyme this is alwaysregarded as acceptor, even if this direction of the reaction is not readilydemonstrated. The only exception is the subclass EC 1.6, in which NAD(P)H isthe donor; some other redox catalyst is the acceptor.
Althoughnot used as a criterion for classification, the two hydrogen atoms at carbon-4of the dihydropyridine ring of nicotinamide nucleotides are not equivalent inthat the hydrogen is transferred stereospecifically.
Transferasesare enzymes transferring a group, e.g. a methyl group or a glycosylgroup, from one compound (generally regarded as donor) to another compound(generally regarded as acceptor). The systematic names are formed according tothe scheme donor:acceptor grouptransferase. The common names arenormally formed according to acceptor grouptransferase or donorgrouptransferase. In many cases, the donor is a cofactor (coenzyme) chargedwith the group to be transferred. A special case is that of the transaminases(see below).
Sometransferase reactions can be viewed in different ways. For example, the enzyme-catalyzedreaction
X-Y + Z = X + Z-Y
maybe regarded either as a transfer of the group Y from X to Z, or as a breakingof the X-Y bond by the introduction of Z. Where Z represents phosphate orarsenate, the process is often spoken of as 'phosphorolysis' or 'arsenolysis',respectively, and a number of enzyme names based on the pattern of phosphorylasehave come into use. These names are not suitable for a systematic nomenclature,because there is no reason to single out these particular enzymes from theother transferases, and it is better to regard them simply as Y-transferases.
Inthe above reaction, the group transferred is usually exchanged, at leastformally, for hydrogen, so that the equation could more strictly be written as:
X-Y + Z-H = X-H + Z-Y.
Anotherproblem is posed in enzyme-catalyzed transaminations, where the -NH2 group and-H are transferred to a compound containing a carbonyl group in exchange forthe =O of that group, according to the general equation:
R1-CH(-NH2)-R2 + R3-CO-R4 R1-CO-R2 + R3-CH(-NH2)-R4.
Thereaction can be considered formally as oxidative deamination of the donor (e.g.amino acid) linked with reductive amination of the acceptor (e.g. oxoacid), and the transaminating enzymes (pyridoxal-phosphate proteins) might beclassified as oxidoreductases. However, the unique distinctive feature of thereaction is the transfer of the amino group (by a well-established mechanisminvolving covalent substrate-coenzyme intermediates), which justifiedallocation of these enzymes among the transferases as a special subclass (EC2.6.1, transaminases).
Thesecond figure in the code number of transferases indicates the grouptransferred; a one-carbon group in EC 2.1, an aldehydic or ketonic group in EC2.2, an acyl group in EC 2.3 and so on.
Thethird 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.
Theseenzymes catalyze the hydrolytic cleavage of C-O, C-N, C-C and some other bonds,including phosphoric anhydride bonds. Although the systematic name alwaysincludes hydrolase, the common name is, in many cases, formed by thename of the substrate with the suffix -ase. It is understood that thename of the substrate with this suffix means a hydrolytic enzyme.
Anumber of hydrolases acting on ester, glycosyl, peptide, amide or other bondsare known to catalyze not only hydrolytic removal of a particular group fromtheir substrates, but likewise the transfer of this group to suitable acceptormolecules. In principle, all hydrolytic enzymes might be classified astransferases, since hydrolysis itself can be regarded as transfer of a specificgroup to water as the acceptor. Yet, in most cases, the reaction with water asthe acceptor was discovered earlier and is considered as the main physiologicalfunction of the enzyme. This is why such enzymes are classified as hydrolasesrather than as transferases.
Somehydrolases (especially some of the esterases and glycosidases) pose problemsbecause they have a very wide specificity and it is not easy to decide if twopreparations described by different authors (perhaps from different sources)have the same catalytic properties, or if they should be listed under separateentries. An example is vitamin A esterase (formerly EC 18.104.22.168, nowbelieved to be identical with EC 22.214.171.124). To some extent the choice must bearbitrary; however, separate entries should be given only when thespecificities are sufficiently different.
Anotherproblem is that proteinases have 'esterolytic' action; they usually hydrolyseester bonds in appropriate substrates even more rapidly than natural peptidebonds. In this case, classification among the peptide hydrolases is based onhistorical priority and presumed physiological function.
Thesecond figure in the code number of the hydrolases indicates the nature of thebond hydrolysed; EC 3.1 are the esterases; EC 3.2 the glycosylases,and so on.
Thethird figure normally specifies the nature of the substrate, e.g. in theesterases the carboxylic ester hydrolases (EC 3.1.1), thiolesterhydrolases (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-peptidehydrolases the third figure is based on the catalytic mechanism as shown byactive centre studies or the effect of pH.
Lyasesare enzymes cleaving C-C, C-O, C-N, and other bonds by elimination, leavingdouble bonds or rings, or conversely adding groups to double bonds. Thesystematic name is formed according to the pattern substrate group-lyase.The hyphen is an important part of the name, and to avoid confusion should notbe omitted, e.g. hydro-lyase not 'hydrolyase'. In the common names,expressions like decarboxylase, aldolase, dehydratase (in case ofelimination of CO2, aldehyde, or water) are used. In cases where the reversereaction is much more important, or the only one demonstrated, synthase(not synthetase) may be used in the name. Various subclasses of the lyasesinclude pyridoxal-phosphate enzymes that catalyze the elimination of a β- orγ-substituent from an α-amino acid followed by a replacement of thissubstituent by some other group. In the overall replacement reaction, nounsaturated end-product is formed; therefore, these enzymes might formally beclassified as alkyl-transferases (EC 2.5.1...). However, there is ampleevidence that the replacement is a two-step reaction involving the transientformation of enzyme-bound α,β(or β,γ)-unsaturated amino acids. According to therule that the first reaction is indicative for classification, these enzymesare correctly classified as lyases. Examples are tryptophan synthase(EC 126.96.36.199) and cystathionine β-synthase (EC 188.8.131.52).
Thesecond figure in the code number indicates the bond broken: EC 4.1 iscarbon-carbon lyases, EC 4.2 carbon-oxygen lyases and so on.
Thethird figure gives further information on the group eliminated (e.g. CO2 in EC4.1.1, H2O in EC 4.2.1).
Theseenzymes catalyze geometric or structural changes within one molecule. Accordingto the type of isomerism, they may be called racemases, epimerases,cis-trans-isomerases, isomerases, tautomerases, mutases orcycloisomerases.
Insome cases, the interconversion in the substrate is brought about by anintramolecular oxidoreduction (EC 5.3); since hydrogen donor and acceptor arethe same molecule, and no oxidized product appears, they are not classified asoxidoreductases, even though they may contain firmly bound NAD(P)+.
Thesubclasses are formed according to the type of isomerism, the sub-subclasses tothe type of substrates.
Ligasesare enzymes catalyzing the joining together of two molecules coupled with thehydrolysis of a diphosphate bond in ATP or a similar triphosphate. Thesystematic names are formed on the system X:Y ligase (ADP-forming). Inearlier editions of the list the term synthetase has been used for thecommon 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 itis desired to emphasis the synthetic nature of the reaction). ConsequentlyNC-IUB decided in 1983 to abandon the use of synthetase for common names, andto replace them with names of the type X-Y ligase. In a few cases inGroup 6, where the reaction is more complex or there is a common name for theproduct, a synthase name is used (e.g. EC 184.108.40.206 and EC 220.127.116.11).
Itis recommended that if the term synthetase is used by authors, it shouldcontinue to be restricted to the ligase group.
Thesecond figure in the code number indicates the bond formed: EC 6.1 for C-Obonds (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.
Ina few cases it is necessary to use the word other in the description ofsubclasses and sub-subclasses. They have been provisionally given the figure99, in order to leave space for new subdivisions.
Fromtime to time, some enzymes have been deleted from the List, while some othershave been renumbered. However, the old numbers have not beenallotted to new enzymes; rather the place has been left vacant andcross-reference is made according to the following scheme:
[EC18.104.22.168 Deleted entry: old name]
[EC22.214.171.124 Transferred entry: now EC 126.96.36.199 - common name].
Entriesfor reclassified enzymes transferred from one position in the List to anotherare followed, for reference, by a comment indicating the former number.
Itis regarded as important that the same policy be followed in future revisionsand extensions of the Enzyme List, which may become necessary from time totime.
4.Rules for Classification and Nomenclature
(a)General Rules for Systematic Names and Guidelines for Common Names
Generallyaccepted 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, unlessambiguity would be caused. In general, it is not necessary to indicatepositions of substituents in common names, unless it is necessary to preventtwo different enzymes having the same name. The prefix keto is no longerused for derivatives of sugars in which -CHOH- has been replaced by -CO-; theyare named throughout as dehydro-sugars.
Toproduce usable systematic names, accepted trivial names of substrates formingpart of the enzyme names should be used. Where no accepted and convenienttrivial names exist, the official IUPAC rules of nomenclature should be appliedto the substrate name. The 1,2,3 system of locating substituents should be usedinstead 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 shouldnormally 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 ketoacids) may be used as a class name, and for individual compounds in which -CH2- has beenreplaced by -CO-, oxo should be used.
Wherethe substrate is normally in the form of an anion, its name should end in -aterather than -ic; e.g. lactate dehydrogenase, not 'lactic dehydrogenase'or 'lactic acid dehydrogenase'.
Commonlyused abbreviations for substrates, e.g. ATP, may be used in names ofenzymes, but the use of new abbreviations (not listed in recommendations of theIUPAC-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.
Namesof substrates composed of two nouns, such as glucose phosphate, which arenormally written with a space, should be hyphenated when they form part of theenzyme names, and thus become adjectives, e.g. glucose-6-phosphate1-dehydrogenase (EC 188.8.131.52). This follows standard practice in phraseswhere two nouns qualify a third; see, for example, Handbook for ChemicalSociety Authors, 2nd edn, p. 14 (The Chemical Society, London, 1961).
Theuse as enzyme names of descriptions such as condensing enzyme,acetate-activating enzyme, pH 5 enzyme should be discontinued as soon asthe catalyzed reaction is known. The word activating should not be usedin 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 thissense may lead to confusion.
Ifit can be avoided, a common name should not be based on a substance that is nota true substrate, e.g. enzyme EC 184.108.40.206 should not be called'crotonase', since it does not act on crotonate.
Wherea name in common use gives some indication of the reaction and is not incorrector ambiguous, its continued use is recommended. In other cases a common name isbased 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 convenientuse. A few names of proteolytic enzymes ending in -in are retained; allother enzyme names should end in -ase.
Systematicnames consist of two parts. The first contains the name of the substrate or, inthe 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.
Anumber of generic words indicating a type of reaction may be used in eithercommon or systematic names: oxidoreductase, oxygenase, transferase (witha prefix indicating the nature of the group transferred), hydrolase, lyase,racemase, epimerase, isomerase, mutase, ligase.
Anumber of additional generic words indicating reaction types are used in commonnames, but not in the systematic nomenclature, e.g. dehydrogenase,reductase, oxidase, peroxidase, kinase, tautomerase, deaminase, dehydratase,etc..
Whereadditional information is needed to make the reaction clear, a phraseindicating the reaction or a product should be added in parentheses after thesecond part of the name e.g. (ADP-forming), (dimerizing), (CoA-acylating).
Thedirect attachment of -ase to the name of the substrate will indicatethat the enzyme brings about hydrolysis.
Thesuffix -ase should never be attached directly to the name of thesubstrate.
Thename 'dehydrase' which was at one time used for both dehydrogenating anddehydrating enzymes, should not be used. Dehydrogenase will be used forthe former and dehydratase for the latter.
Wherepossible, common names should normally be based on a reaction direction thathas been demonstrated, e.g. dehydrogenase or reductase, decarboxylaseor carboxylase.
Inthe case of reversible reactions, the direction chosen for naming should be thesame for all the enzymes in a given class, even if this direction has not beendemonstrated for all. Thus, systematic names may be based on a writtenreaction, even though only the reverse of this has been actually demonstratedexperimentally.
Whenthe overall reaction includes two different changes, e.g. an oxidativedemethylation, the classification and systematic name should be based, wheneverpossible, on the one (or the first one) catalyzed by the enzyme; the otherfunction(s) should be indicated by adding a suitable participle in parentheses,as in the case of sarcosine:oxygen oxidoreductase (demethylating) (EC220.127.116.11); D-aspartate:oxygenoxidoreductase (deaminating) (EC 18.104.22.168); L-serine hydro-lyase (adding indoleglycerol-phosphate)(EC 22.214.171.124).
Otherexamples of such additions are (decarboxylating), (cyclizing),(acceptor-acylating), (isomerizing).
Whenan enzyme catalyzes more than one type of reaction, the name should normallyrefer to one reaction only. Each case must be considered on its merits, and thechoice must be, to some extent, arbitrary. Other important activities of theenzyme may be indicated in the List under 'Reaction' or 'Comments'.
Similarly,when any enzyme acts on more than one substrate (or pair of substrates), thename 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 wholegroup of substrates, or an alternative substrate may be given in parentheses.
Agroup of enzymes with closely similar specificities should normally bedescribed by a single entry. However, when the specificity of two enzymes catalyzingthe same reactions is sufficiently different (the degree of difference being amatter of arbitrary choice) two separate entries may be made, e.g. EC126.96.36.199 and EC 188.8.131.52. Separate entries are also appropriate for enzymeshaving similar catalytic functions, but known to differ basically with regardto reaction mechanism or to the nature of the catalytic groups, e.g. amineoxidase (flavin-containing) (EC 184.108.40.206) and amine oxidase(copper-containing) (EC 220.127.116.11).
(b)Rules and Guidelines for Particular Classes of Enzymes
Theterms dehydrogenase or reductase will be used much as hitherto.The latter term is appropriate when hydrogen transfer from the substancementioned as donor in the systematic name is not readily demonstrated. Transhydrogenasemay be retained for a few well-established cases. Oxidase is used onlyfor cases there O2 acts as an acceptor, and oxygenase only for thosecases where the O2 molecule (or part of it) is directly incorporated into thesubstrate. Peroxidase is used for enzymes using H2O2 asacceptor. Catalase must be regarded as exceptional. Where no ambiguityis caused, the second reactant is not usually named; but where required toprevent ambiguity, it may be given in parentheses, e.g. EC 18.104.22.168, alcoholdehydrogenase and EC 22.214.171.124, alcohol dehydrogenase (NADP+).
Allenzymes catalyzing oxidoreductions should be named oxidoreductases inthe systematic nomenclature, and the names formed on the pattern donor:acceptoroxidoreductase.
Foroxidoreductases using NAD+ or NADP+, the coenzyme should always be named as the acceptor exceptfor the special case of Section 1.6 (enzymes whose normal physiologicalfunction is regarded as reoxidation of the reduced coenzyme). Where the enzymecan use either coenzyme, this should be indicated by writing NAD(P)+.
Wherethe true acceptor is unknown and the oxidoreductase has only been shown toreact with artificial acceptors, the word acceptor should be written inparentheses, as in the case of EC 126.96.36.199, succinate:(acceptor)oxidoreductase.
Oxidoreductasesthat bring about the incorporation of molecular oxygen into one donor or intoeither or both of a pair of donors are named oxygenase. If only one atomof oxygen is incorporated the term monooxygenase is used; if both atomsof O2 are incorporated, the term dioxygenase is used.
Oxidoreductasesbringing about the incorporation of oxygen into one of paired donors should benamed on the pattern donor,donor:oxygen oxidoreductase (hydroxylating).
Onlyone specific substrate or reaction product is generally indicated in the commonnames, together with the group donated or accepted.
Theforms transaminase, etc., may be replaced if desired by thecorresponding forms aminotransferase, etc..
Anumber of special words are used to indicate reaction types, e.g. kinaseto indicate a phosphate transfer from ATP to the named substrate (not'phosphokinase'), diphosphokinase for a similar transfer of diphosphate.
Enzymescatalyzing group-transfer reactions should be named transferase and thenames formed on the pattern donor:acceptor group-transferred-transferase,e.g. ATP:acetate phosphotransferase (EC 188.8.131.52). A figure may be prefixedto show the position to which the group is transferred, e.g. ATP:D-fructose 1-phosphotransferase (EC 184.108.40.206). The spelling 'transphorase' should not beused. In the case of the phosphotransferases, ATP should always be named as thedonor. In the case of the transaminases involving 2-oxoglutarate, the lattershould always be named as the acceptor.
Theprefix denoting the group transferred should, as far as possible, benon-committal with respect to the mechanism of the transfer, e.g. phospho-,rather than phosphate-.
Thedirect addition of -ase to the name of the substrate generally denotes ahydrolase. Where this is difficult, e.g. for EC 220.127.116.11, the word hydrolasemay be used. Enzymes should not normally be given separate names merely on thebasis of optimal conditions for activity. The acid and alkaline phosphatases(EC 18.104.22.168-2) should be regarded as special cases and not as examples to befollowed. The common name lysozyme is also exceptional.
Hydrolysingenzymes should be systematically named on the pattern substrate hydrolase.Where the enzyme is specific for the removal of a particular group, the groupmay be named as a prefix, e.g. adenosine aminohydrolase (EC 22.214.171.124). Ina number of cases this group can also be transferred by the enzyme to othermolecules, and the hydrolysis itself might be regarded as a transfer of thegroup to water.
Theold names decarboxylase, aldolase, etc., are retained; and dehydratase(not 'dehydrase') is used for the hydro-lyases. 'Synthetase' should not be usedfor any enzymes in this class. The term synthase may be used instead forany enzyme in this class (or any other class) when it is desired to emphasizethe synthetic aspect of the reaction.
Enzymesremoving groups from substrates non-hydrolytically, leaving double bonds (oradding groups to double bonds) should be called lyases in the systematicnomenclature. Prefixes such as hydro-, ammonia- should be used to denotethe type of reaction, e.g. (S)-malate hydro-lyase (EC 126.96.36.199).Decarboxylases should be regarded as carboxy-lyases. A hyphen shouldalways be written before lyase to avoid confusion with hydrolases,carboxylases, etc.
Wherethe equilibrium warrants it, or where the enzyme has long been named after aparticular substrate, the reverse reaction may be taken as the basis of thename, using hydratase, carboxylase, etc., e.g. fumarate hydratase for EC188.8.131.52 (in preference to 'fumarase', which suggests an enzyme hydrolysingfumarate).
Thecomplete molecule, not either of the parts into which it is separated, shouldbe named as the substrate.
Thepart indicated as a prefix to -lyase is the more characteristic andusually, but not always, the smaller of the two reaction products. This mayeither 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.
Varioussubclasses of the lyases include a number of strictly specific orgroup-specific pyridoxal-5-phosphate enzymes that catalyze eliminationreactions of β- or γ-substituted α-amino acids. Some closely relatedpyridoxal-5-phosphate-containing enzymes, e.g. tryptophan synthase (EC184.108.40.206) and cystathionine β-synthase (EC 220.127.116.11) catalyze replacementreactions in which a β- or γ-substituent is replaced by a second reactantwithout creating a double bond. Formally, these enzymes appear to betransferases rather than lyases. However, there is evidence that in these casesthe elimination of the β- or γ-substituent and the formation of an unsaturatedintermediate is the first step in the reaction. Thus, applying rule 14, theseenzymes are correctly classified as lyases.
Inthis class, the common names are, in general, similar to the systematic nameswhich indicate the basis of classification.
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 18.104.22.168), phenylpyruvateketo-enol-isomerase (EC 22.214.171.124), 3-oxosteroid Δ5-Δ4-isomerase(EC 126.96.36.199). Enzymes catalyzing an aldose-ketose interconversion will be knownas aldose-ketose-isomerases, e.g. L-arabinose aldose-ketose-isomerase(EC 188.8.131.52). When the isomerization consists of an intramolecular transfer ofa group, the enzyme is named a mutase, e.g. EC 184.108.40.206, and the phosphomutasesin sub-subclass 5.4.2; when it consists of an intramolecular lyase-typereaction, e.g. EC 220.127.116.11, it is systematically named a lyase (decyclizing).
Isomerasescatalyzing inversions at asymmetric centres should be termed racemasesor epimerases, according to whether the substrate contains one, or morethan one, centre of asymmetry: compare, for example, EC 18.104.22.168 with EC22.214.171.124. A numerical prefix to the word epimerase should be used to showthe position of the inversion.
Commonnames for enzymes of this class were previously of the type XY synthetase.However, as this use has not always been understood and synthetase has beenconfused with synthase (see Rule 24), it is now recommended that as far aspossible the common names should be similar in form to the systematic names.
Theclass of enzymes catalyzing the linking together of two molecules, coupled withthe breaking of a diphosphate link in ATP, etc. should be known as ligases.These enzymes were often previously known as 'synthetases'; however, thisterminology differs from all other systematic enzyme names in that it is basedon the product and not on the substrate. For these reasons, a new systematicclass name was necessary.
Thecommon names should be formed on the pattern X-Y ligase, where X-Y isthe substance formed by linking X and Y. In certain cases, where a trivial nameis commonly used for XY, a name of the type XY synthase may berecommended (e.g. EC 126.96.36.199, carnosine synthase).
Thesystematic 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 inparentheses indicates both that ATP is the triphosphate involved, and also thatthe terminal diphosphate link in broken. Thus, the reaction is X + Y + ATP =X-Y + ADP + Pi.
Inthe special case where glutamine acts as an ammonia-donor, this is indicated byadding in parentheses (glutamine-hydrolysing) to a ligase name.
Inthis case, the name amido-ligase should be used in the systematicnomenclature.