In view of this state of affairs, the General Assembly of the International Union of Biochemistry (IUB) decided, during the third International Congress of Biochemistry in Brussels in August, 1955, to set up an International Commission on Enzymes. This step was taken in consultation with the International Union of Pure and Applied Chemistry (IUPAC).
The International Commission on Enzymes was established in 1956 by the President of the International Union of Biochemistry, Professor M. Florkin, with the advice of an ad hoc Committee. The following members were appointed by the Bureau of the International Union of Biochemistry:
A.E. Braunstein, U.S.S.R.; S.P. Colowick, U.S.A.; P.A.E. Desnuelle, France; M. Dixon, U.K. (President); V.A. Engelhardt, U.S.S.R.; E.F. Gale, U.K.; O. Hoffmann-Ostenhof, Austria; A.L. Lehninger, U.S.A.; K. Linderstrom-Lang, Denmark; F. Lynen, Germany.Of these members, O. Hoffmann-Ostenhof had already published a review on the problem (Advances in Enzymology (1953) 14, 219-260) with considerable progress towards a classification, and M. Dixon and E.C. Webb had drafted a list for their book, Enzymes, which was to appear in 1958. The Commission brought together these efforts to list enzymes systematically.Corresponding Members: F. Egami, Japan; L.F. Leloir, Argentina.
In 1959, on the death of K. Linderstrom-Lang, E.C. Webb (United Kingdom, later Australia) joined the Commission.
The terms of reference of the Enzyme Commission, as laid down by the ad hoc Committee, were as follows:
'To consider the classification and nomenclature of enzymes and coenzymes, their units of activity and standard methods of assay, together with the symbols used in the description of enzyme kinetics.'The Enzyme Commission faced many difficulties arising from the uncontrolled naming of the rapidly increasing number of known enzymes. Some of the names in use were definitely misleading; others conveyed little or nothing about the nature of the reaction catalysed, as for example, diaphorase, Zwischenferment, catalase. Enzymes catalysing essentially similar reactions had sometimes names implying that they belong to different groups, while some enzymes of different types had been placed in the same group, for example, the pyrophosphorylases had included both glycosyltransferases and phosphotransferases. In some cases a name which had been well established for many years with a definite meaning, such as the term synthetase, had been later employed with different meanings, thus causing confusion.
One of the main tasks given to the Commission was therefore to see how the nomenclature of enzymes could best be brought into a satisfactory state, and whether a code of systematic rules could be devised that would serve as a guide for the consistent naming of new enzymes in the future. At the same time, the Commission realized the difficulties that would be caused by a large number of changes of well-known enzyme names, and the desirability of retaining the existing names wherever there was no good reason for making an alteration. Nevertheless, the overriding consideration was to reduce the confusion and prevent further confusion from arising. Its task could not have been accomplished without causing some inconvenience, for this was the inevitable result of having allowed the problem to drift for a considerable time.
Throughout its work, the Enzyme Commission was in close touch with the Biological Chemistry Nomenclature Commission of IUPAC. In addition, it considered many comments and suggestions from various experts in the field; 52 formal documents were circulated and discussed in several meetings. Finally, the Commission prepared a report, which was presented to the General Assembly of the International Union of Biochemistry at their meeting in Moscow in 1961, and was adopted for publication by Pergamon Press of Oxford. The nomenclature set out in that report has been widely used in scientific journals, textbooks, etc. since 1961.
Subsequently, the Council of IUB dissolved the Commission on Enzymes and set up a Standing Committee on Enzymes consisting of S.P. Colowick, O. Hoffmann-Ostenhof, A.L. Lehninger and E.C. Webb (Secretary). This Standing Committee discussed the comments and criticisms received on the published report of the Enzyme Commission and prepared in 1964 a second version, the Recommendations (1964) of the International Union of Biochemistry on the Nomenclature and Classification of Enzymes. This edition was published by Elsevier Publishing Company of Amsterdam; it also became Volume 13 of Comprehensive Biochemistry (Florkin, M. & Stotz, E.H., ed.), published by Elsevier.
The function of the Standing Committee on Enzymes was then taken over by the IUPAC/IUB Commission on Biochemical Nomenclature (CBN). This Commission was originally set up to deal with the nomenclature of various compounds of biochemical interest. At a meeting in September, 1969, it was decided that the Recommendations on Enzyme Nomenclature should be revised, mainly to include the many enzymes discovered in recent years, and an Expert Committee on Enzymes was formed, consisting of A.E. Braunstein, J.S. Fruton, O. Hoffmann-Ostenhof, B.L. Horecker, W.B. Jakoby, P. Karlson, B. Keil, E.C. Slater, E.C. Webb (convener) and W.J. Whelan. With the help of a number of expert subcommittees, and comments and suggestions solicited from authors and editors, a completely revised version of Enzyme Nomenclature was prepared and published by Elsevier Publishing Company as Recommendations (1972) of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry. Once again it was also published as Volume 13 of Comprehensive Biochemistry.
After the publication of the third version of the complete report and enzyme list, the Commission on Biochemical Nomenclature decided that it would be appropriate to publish from time to time a Supplement to the Enzyme List, containing new entries, deletions and corrections. The first supplement was prepared during 1974-5 and published in Biochimica et Biophysica Acta (1976) 429, 1-45.
In 1977 the Nomenclature Committee of IUB (NC-IUB) was set up and responsibility for enzyme nomenclature passed to it. In this task it has worked closely with the IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The 1978 recommendations, published by Academic Press in 1979, were prepared with considerable help from the Division of Computor Research and Technology of the U.S. National Institutes of Health, under the direction of Richard J. Feldmann.
Following the publication of the 1978 edition, the work of updating the enzyme list continued steadily, and NC-IUB published four supplements in the European Journal of Biochemistry: (1980) 104, 1-4; (1981) 116, 423-435; (1982) 125, 1-13; (1983) 131, 461-472. It was agreed in 1982 that the number of changes to existing entries, together with a substantial number of new entries, justified a completely new edition and this was published by Academic Press towards the end of 1984.
Since 1984 three further supplements have been published in the European Journal of Biochemistry: ((1986) 157, 1-26; (1989) 179, 489-533; (1990) 187, 263-281). The additional entries to the enzyme list in these supplements, together with improvements to older entries proposed by individual authors or small groups of workers, were incorporated into a draft of the present volume by Edwin Webb. The final version was approved at a meeting of NC-IUB in May, 1991.
The Enzyme List in the sixth edition contains 3540 entries, of which 178 record enzymes which are now transferred elsewhere in the list, and 166 have been deleted completely. Thus the number of enzymes actually listed is 3196, an increase of 29% on the 1984 edition.
The size of the list has increased steadily since the publication of the Report of the Enzyme Commission, as shown in the following figures for 'live' entries:
| Report of the Enzyme Commision (1961) | 712 |
| Enzyme Nomenclature (1964) | 875 |
| Enzyme Nomenclature (1972) | 1770 |
| Enzyme Nomenclature (1978) | 2122 |
| Enzyme Nomenclature (1984) | 2477 |
| Enzyme Nomenclature (1992) | 3196 |
In recent years Kurt Loening has arranged the compilation by John Wittorf of an annual list of enzyme names from Chemical Abstracts which do not appear to be listed in Enzyme Nomenclature. These lists have proved to be a valuable base for further searches of the literature.
Not all sections of the enzyme list have received the same attention at each revision. For the present edition, subclass EC 3.4, the peptidases, has undergone the most thorough revision, based on the recommendations of an expert panel appointed by NC-IUB in 1989. The panel, consisting of A.J. Barrett (convener), J.S. Bond, F. Fiedler, J.K. McDonald, L. Polgár, S. Wilk and J.F. Woessner, Jr, revised the preamble to subclass 3.4, and recommended the deletion of 51 of the previous entries, the transfer of 50 enzymes to other numbers, and the inclusion of 56 entirely new entries.
It is the intention of NC-IUBMB to commission similar 'in depth' revision of sections of the enzyme list from time to time. A number of expert panels are being set up now to review some sections before the next edition of Enzyme Nomenclature is due. These include transaminases (EC 2.6.1), kinases (EC 2.7.1), nucleases (EC 3.1.11-31), lipases, ribozymes, and protein kinases and protein phosphatases. Biochemists who feel able to contribute in these areas are invited to write to Professor K.F. Tipton, Department of Biochemistry, Trinity College, Dublin 2, Republic of Ireland, who will be co-ordinating the activities of NC-IUB in the field of enzyme nomenclature.