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History |
1 Department of Standardization in Laboratory Medicine, H:S Frederiksberg Hospital, Copenhagen Hospital Corporation, Nordre Fasanvej 57, DK-2000 Frederiksberg, Denmark. Fax 45-38-16-38-79.
Abstract
Background: The "unit" for "enzymic activity" (U = 1 µmol/min) was recommended by the International Union of Biochemistry and Molecular Biology (IUB) in 1961 and is widely used in medical laboratory reports. The general trend in metrology, however, is toward global standardization through defining units coherent with the International System of Units (SI).
Approach: Several proposals were advanced from the IFCC, International Union of Pure and Applied Chemistry, and IUB regarding the definition for enzymic activity as well as the terms for kind-of-quantity, units, symbol, and dimension. In 1977, international agreement was reached between these bodies and WHO that "catalytic activity" (z), of a catalyst in a given system is defined by the rate of conversion in a measuring system (in mol/s) and expressed in "katal" (symbol, kat; equal to 1 mol/s). The katal is invariant of the measurement procedure, but the numerical quantity value is not. Gaining support for the katal from the final arbiter, the General Conference on Weights and Measures, was slow, but Resolution 12 of 1999 adopted the katal (symbol, kat) as a special name and symbol for the SI-derived unit, mol/s, used in measuring catalytic activity.
Conclusions: Laboratory results for amounts of catalysts, including enzymes, measured by their catalytic activity can now officially be expressed in katals and are traceable to the SI provided that the specified indicator reaction reflects first-order kinetics. The conversion from "unit" is: 1 U = 16.667 x 10-9 kat. Further derived quantities have coherent units such as kat/L, kat/kg, and kat/kat = 1.
Measurements of amounts, concentrations, or fractions of inorganic and organic catalysts are important in science and technology of many fields, not least for enzymes in laboratory medicine.
In principle, the amount of an enzyme can be described by number of entities (unit, 1), amount of substance (unit, mole), or mass (unit, kilogram). For practical reasons, however, the catalytic effect of the enzyme is often chosen instead. The task then is to measure the increase in the rate of conversion of a defined chemical reaction, preferably of the first order, under strictly controlled conditions.
Much ingenuity has gone into selecting suitable, sometimes sequential, reaction mechanisms, indicators, and signals for each enzyme, and this has often been reflected in the measurement units used for expression of results.
A classical example is the "King-Armstrong unit" 1 for alkaline phosphatase (EC 3.1.3.1), defined by these pioneers as the amount of enzyme that, when allowed to act on excess disodium phenylphosphatase at pH 9.0 for 30 min at 37.5°C, will liberate 1 mg of phenol (1). Naturally, a definition of this type restricts the applicability of the unit to the particular enzyme and measurement procedure.
Although the measurement result for a given measurand will always depend on the measurement procedure, comparisons would be easier with a universally agreed unit for catalytic activity. The quest for acceptance of such a unit at the highest metrologic level was more arduous and protracted than anticipated.
Global Units Noncoherent with the SI (from 1955)
The first proposal was created in the bosom of the National Academy of Sciences (US) as formulated 1958 by the Subcommittee on Enzymes of the Committee on Biological Chemistry in the Division of Chemistry and Chemical Technology (2):
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This definition was soon supported by the Commission of Enzymes within the International Union of Biochemistry (IUB)
2
in a report (3) and finally in IUB Recommendations 1964 (4) as:
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The structure and magnitude of this unit were obviously chosen to correspond with the typical duration of enzymatic reactions, which are measured in minutes rather than seconds, and so that numerical values would be of a convenient size. The term, symbol, and conversion (1 U = 16.67 nmol/s) of this unit would clearly be unacceptable to the ultimate arbiter on units and prefixes of the International System of Units (SI), i.e., the intergovernmental diplomatic General Conference on Weights and Measures (CGPM), for several reasons:
On the other hand, the IUB "(enzyme) unit" has been used extensively in biochemistry and clinical chemistry for reporting results.
A half-way alignment with the SI was thus proposed (5) (in translation from Danish):
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Even if the non-SI unit "minute" is ‘accepted for use with the SI’ (6), the size of the proposed unit, 1 EA = 16.67 mmol/s, was noncoherent with the SI; therefore, quite properly this proposal was not furthered.
Global Units Coherent with the SI (from 1962)
A full step toward SI coherency was taken in 1962 when the following definition was proposed (translated from Danish) (7):
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The use of a subscript to indicate the size of the unit, however, is not orthodox and was sagely omitted in subsequent recommendations.
The International Union of Pure and Applied Chemistry (IUPAC) and the IFCC issued two reports in 1966 (8) and 1967 (9), now giving a proper term to the coherent unit, namely:
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A further IUPAC/IFCC Tentative Recommendation in 1972 (10) preferred the etymologically correct spelling of katal (kat) and was in agreement with the IUPAC/IUB Commission on Biochemical Nomenclature. Still, it elicited several individual counterproposals, generally unpublished [detailed in Ref. (11)]. Most were not acceptable to the international recommending bodies.
The kind-of-quantity (also termed ‘quantity in a general sense’) in question is obviously extensive in that double the amount of substance (in moles) changed per time (in seconds) corresponds to double the amount of enzyme, hence the term ‘catalytic amount’. However, the enzymologists of the IUPAC/IUB Commission on Biochemical Nomenclature, in their authoritative Recommendation 1972 (12), although abandoning the "unit of enzyme" (U), for "katal" (kat), 3 preferred the term for the kind-of-quantity ‘enzymic activity’.
‘Catalytic activity’ prevailed (13)(14)(15) in spite of a last stand on ‘catalytic amount’ by the clinical chemists of the IFCC/IUPAC (16). The same group suggested the now accepted symbol, z, for the kind-of-quantity.
The first IUPAC/IFCC reports proposed that the kind-of-quantity should be base, having a unique metrologic dimension, with the catal as the base unit, analogous to length (L) and metre. This idea had to be abandoned because the path to an SI base unit adopted by the CGPM was too narrow, considering that there are only seven base units.
For a time, the IFCC Expert Panel on Enzymes, contrary to the Expert Panel on Quantities and Units, suggested that the special term katal was against the international trend of restricting the number of special terms (17). Notwithstanding the trueness of this opinion, the enzymologists ended the internecine strife by eventually supporting the katal (13).
Thus, the outcome of this period was the general acceptance by the IFCC, IUPAC, and IUB, as well as by the WHO (18)(19) of a special term, katal (symbol, kat) for the SI-coherent derived unit "mole per second" when used with catalytic activity (symbol, z).
The details of the definition of "catalytic activity" continuously varied, but the latest IUPAC/IFCC Recommendation 1995 in "The Silver Book" (20) may serve with slight editorial changes: property of a component measured by its catalyzed amount-of-substance rate of conversion of a specified chemical reaction, in a specified measuring system.
It should be stressed that catalytic activity is defined by the rate of conversion (measured in mol/s), but is not itself a rate of conversion. Catalytic activity is a separate kind-of-quantity pertaining to the catalyst, not the reaction kinetics. In addition, the katal is invariant of the measurement procedure, although the numerical value of a result depends on the procedure. (Analogously, the "metre" is invariant even if the length of a metal strip varies with measuring instrument and temperature.) The measurement procedure is a necessary specification to a quantity if the result is to be meaningful.
The IFCC and the IUPAC are committed to promoting the use of the SI whenever possible, but the ease of using the noncoherent but familiar symbol, U, made routine acceptance of the coherent mol/s or kat difficult.
Approach to the Consultative Committee for Units (1978)
Flushed with the newly achieved international consensus, the IFCC, through the IUPAC, proposed the special term and symbol, katal and kat, to the Consultative Committee for Units (CCU) of the International Committee for Weights and Measures (CIPM). It was hoped that the arguments of reducing the plurality of enzyme units, promoting the SI, and aiding the understanding of medical laboratory results would persuade the CCU. Pertinent analogies were the adopted ‘bequerel’ (Bq = s-1) for activity of a radionuclide rather than ‘curie’ (Ci = 3.7 x 1010 s-1), and ‘gray’ (Gy = J/kg) for absorbed dose or massic energy imparted. The CCU, however, at its meeting in 1978 was not convinced of the need for a special term (21).
This setback did not hinder the adoption of the katal by a few journals, certificates on enzyme reference materials from the European Community Bureau of Reference (BCR), the European Pharmacopoeia (22), the IUPAC/IFCC Compendium of Terminology and Nomenclature of Properties in Clinical Laboratory Sciences (20), and notably the IUPAC/IFCC database of thousands of systematic terms for properties, including those with enzyme analytes (23).
The spread of the katal in routine medical laboratory reporting, however, has been sporadic, and apart from general inertia, the argument was often advanced that the special term lacked adoption by CGPM for use with the SI.
Approach to the CIPM (1998)
Consequently, the IFCC/IUPAC Committee/Commission on Nomenclature, Properties and Units formulated an official IFCC petition, 1998-05, to the CIPM (24), arguing that the term katal (a) suggests a property of a catalyst rather than of a chemical reaction; (b) allows the presentation of values in laboratory medicine of, e.g., enzyme concentration in "katal per litre" rather than "mole per second and litre", which is difficult to transmit and comprehend for most healthcare personnel; and (c) promotes and facilitates the use of SI-coherent units rather than the "unit" symbolized as U (1 µmol·min-1).
The CIPM obviously needed advice and transmitted the petition to the CCU.
Response of the CCU (1998)
At the 13th CCU meeting in September 1998, the author presented the issue on behalf of the IFCC (24). Although there was some concern that a proliferation of special terms should be avoided, it was argued that, whereas the physicists had numerous such terms, the chemists and biologists had been relatively neglected by the SI and that ‘any recommendations coming from those communities should be carefully considered’ [page 99 in Ref. (25)]. In the end, the CCU penned Recommendation U 1 (1998) ‘Special name for the SI unit mole per second, the katal, for the expression of catalytic activity’ [page 54 in Ref. (25)]. The arguments were (a) the importance for human health and safety of promoting and facilitating the use of SI in the field of medicine and biochemistry; (b) avoiding the use of non-SI units, such as "unit" (U); and (c) recommendation by international unions.
Response of the CCQM (1999)
This recommendation was well received by the CIPM, but because the unit was of a chemical nature, a further opinion was sought of the Consultative Committee for Amount of Substance (CCQM), in effect a committee on chemistry. At the group’s fifth meeting in February 1999, the IFCC petition was again presented together with a preceding exchange of letters between two members and the author (26). CCU Recommendation U 1 was supported with the further recommendations (27) that ‘when the katal is used the measurand must be specified by reference to the measurement procedure, which must identify the indicator reaction’.
CGPM Resolution 12 of 1999
Finally, the IFCC petition and the related CCU and CCQM Recommendations were put before the 21st CGPM meeting in October 1999, which adopted the combined recommendations summarized above.
As consequence, the International Bureau of Weights and Measures added to Table 3, SI derived units with special names and symbols, of the authoritative book The International System of Units (28) a new line:
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and to Table 4
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(The unit kat/l or kat/L is also accepted for use with the SI.)
Conclusions
The katal is now adopted under the Convention of the Metre of 1875 by the highest metrologic authority, the intergovernmental diplomatic CGPM, to express quantity values of catalytic activity of enzymes and other catalysts in any field of science and technology. Further derived kinds-of-quantity and derived units may be defined in the conventional manners.
Thus, we now have, for example:
If the measurement procedure has an indicator reaction that can be described by conversion of amount of substances of reactants, the results involving the katal are metrologically traceable to the SI and thereby comparable across time and space. For such results, the conversion from the IUB unit, U, to katal is:
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Journals subscribing to the preferred use of SI units can now with the blessing of the CGPM promote international standardization of units by including the katal in their Information for Authors, thus facilitating the globalization of medicine.
Footnotes
1 In this text double quotation marks are used for concepts, single quotation marks for terms and quotes. 
2 Nonstandard abbreviations: IUB, International Union of Biochemistry and Molecular Biology; SI, International System of Units; CGPM, General Conference on Weights and Measures; IUPAC, International Union of Pure and Applied Chemistry; CCU, Consultative Committee for Units; CIPM, International Committee for Weights and Measures; and CCQM, Consultative Committee for Amount of Substance.
3 The agreement between the IFCC/IUPAC/IUB specialists in the IUPAC/IUB Commission on Biochemical Nomenclature on the special term katal (symbol, kat) was properly celebrated at a commission meal in Menton, France, where the local chef had been inveigled into presenting a large cake with the appropriate term inscribed on the icing. If my memory is correct, there was also a drawing of a feline.
4 The stress is supposed to fall on the last syllable.
References
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