Commission on Enzymes of the International

Classification of Enzymes. A systematic classification and nomenclature has been established by the Commission on Enzymes of the International Union of Biochemistry (6), which divides enzymes into six general groups ... 

In accordance with the recommendations of the commission on enzymes of the International Union of Biochemistry (see Nature 188, 464-466, I960 Science 182, 1548-1550, 1960 and Report of the Commission on Enzymes of the International Union of Biochemistry 1961, I.U.B. Symposium Series, Vol. 20, Pergamon Press, London) nicotinamide-adenine dinucleotide (NAD) has been substituted fordiphosphopyridine nucleotide (DPN) nicotinamide-adenine dinuoleotide, reduced form (NADHj), for diphosphopyridiiie nucleotide, reduced form (DPNH) nicotinamide-adenine diuu-cleotide phosphate (NADP), for triphosphopyridine nucleotide (TPN) and nicotinamide-adenine dinucleotide phosphate, reduced form (NADPH2), for triphosphopyridine nucleotide, reduced form (TPNH). 

In many situations, the actual molar amount of the enzyme is not known. However, its amount can be expressed in terms of the activity observed. The International Commission on Enzymes defines One International Unit of enzyme as the amount that catalyzes the formation of one micromole of product in one minute. (Because enzymes are very sensitive to factors such as pH, temperature, and ionic strength, the conditions of assay must be specified.) Another definition for units of enzyme activity is the katal. One katal is that amount of enzyme catalyzing the conversion of one mole of substrate to product in one second. Thus, one katal equals 6X10 international units. 

In this volume, the Editors have compiled a group of articles that they feel represents a continuation of the aims of this publication to provide the clinical chemist with reviews of state-of-the-art methodology, newer areas of medicine and physiology that affect the clinical chemist, and those areas related to the latest information relating ehemistry to disease. Brown, Kalow, Pilz, Whittaker, and Woronick present an article entitled The Plasma Cholinesterases A New Perspective. This is truly an international effort and is presented by the authors on behalf of the Commission on Toxicology of the Clinical Chemistry Division of the International Union of Pure and Applied Chemistry. It provides a superb review of human serum cholinesterase and its variants and a critical assessment of the physical and chemical properties of the enzyme. 

Standard abbreviations used in both the biochemical and chemical literature have been employed in the text and are listed in the Biochemical Journal publication, Policy of the Journal and Instructions to Authors issued by the Biochemical Society, London, 1972. Wherever possible enzymes have been named at the first mention by use of the EC (Enzyme Commission) numbers (Recommendations of the International Union of Biochemistry on the nomenclature and classification of Enzymes, Elsevier, Amsterdam, 1965). 

A system based partly on historical names, partly on the substrate, and partly on the type of reaction catalyzed is far from satisfactory. In 1956, the International Union of Biochemistry set up a Commission on Enzymes to consider the classification and nomenclature of enzymes. The Commission presented a report in 1961 whose recommendations for naming and classifying enzymes were subsequently adopted (12). Enzymes are classified on the basis of the reactions they catalyze. Despite its apparent complexities, the system is precise and very descriptive, accommodating existing enzymes and serving as a systematic basis for the naming of new enzymes. AH enzymes are placed in one of the six principal classes. 

The actual molar concentration of an enzyme in a cell-free extract or purified preparation is seldom known. Only if the enzyme is available in a pure crystalline form, carefully weighed, and dissolved in a solvent can the actual molar concentration be accurately known. It is, however, possible to develop a precise and accurate assay for enzyme activity. Consequently, the amount of a specific enzyme present in solution is most often expressed in units of activity. Three units are in common use, the international unit (IU), the katal, and specific activity. The International Union of Biochemistry Commission on Enzymes has recommended the use of a standard unit, the international unit, or just unit, of enzyme activity. One IU of enzyme corresponds to the amount that catalyzes the transformation of 1 p,mole of substrate to product per minute under specified conditions of pH, temperature, ionic strength, and substrate concentration. If a solution containing... 

The Jhtemationai Union of Biochemistry (TUB) was officially founded in 1953 by an initiative of the British Biochemical Society. At ibis time enzyme standardization was in a chaotic slate, owing to the multiplicity of arbitrarily defined units of enzyme activity and the ilt-dtfned nomenclature. In 1955, the 1UB International Commission on Enzymes was created. This led to an improved enzyme nomoidature, which has been used since 1961, and the definition of the International Unit (LU.) of enzyme activity. 

All enzymes are named according to a classification system designed by the Enzyme Commission (EC) of the International Union of Pure and Applied Chemistry (IUPAC) and based on the type of reaction they catalyze. Each enzyme type has a specific, four-integer EC number and a complex, but unambiguous, name that obviates confusion about enzymes catalyzing similar but not identical reactions. In practice, many enzymes are known by a common name, which is usually derived from the name of its principal, specific reactant, with the suffix -ase added. Some common names do not even have -ase appended, but these tend to be enzymes studied and named before systematic classification of enzymes was undertaken. 

During natural evolution, a broad variety of enzymes has been developed, which are classified according to the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB). Thus, for each type of characterized enzyme an EC (Enzyme Commission) number has been provided (see http // www.expasy.ch/enzyme/). For instance, all hydrolases have EC number 3 and further subdivisions are provided by three additional digits, e.g. all lipases (official name triacylglycerol lipases) have the EC number 3.1.1.3 and are thus distinguished from esterases (official name carboxyl esterases) having the EC number 3.1.1.1. This classification is based on the substrate (and cofactor) specificity of an enzyme only, however often very similar amino acid sequences and also related three-dimensional structures can be observed. 

The International Union of Biochemistry (lUB) established a commission on enzyme nomenclature to adopt a systematic classification and nomenclature of all the existing and yet to be discovered enzymes. This system is based on the substrate and reaction specificity. Although, this International Union of Biochemistry system is complex, it is precise, descriptive and informative. 

In later reports of work using purified enzymes, it was suggested that the erythrocyte enzyme was specific for choline esters and should be called true cholinesterase, while the serum enzyme, which could also hydrolyze noncholine esters, should be called pseudocholinesterase. In fact, both enzymes are to some degree nonspecific, and these names are not recommended by the Commission on Biochemical Nomenclature of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry (12). Instead, the trivial names acetylcholinesterase and cholinesterase should be used for the eiythroe) e and serum enzymes (EC 3.1.1.7 and EC 3.1.1.8, respectively). ... 

International Union of Biochemistry, Report of the Commission on Enzymes (1961), p. 104. Pergamon, Oxford, 1964. 

In 1960, at the general assembly of the International Pharmaceutical Federation (FIP), the obsolescence of various national pharmacopeial methods for assaying pharmaceutical enzymes was demonstrated. An international commission on pharmaceutical enzymes was created to deal with this unsatisfactory situation and develop improved assay methods and guidelines for the preparation of pharmaceutical enzyme reference materials. The Center for Standards has a coordination function in organizing collaborative enzyme assays between academic, industrial, and national pharmaceutical control laboratories and in distributing FIP pharmaceutical enzyme standards. Since 1960, many FIP assay methods and standard preparations have been adopted by national and international pharmacopeias, such as the European Pharmacopoeia. The ultimate goal is to provide official, preferentially nonempirical, standardized assay methods by which comparison of commercially available pharmaceutical enzymes is made possible. The most desirable situation would be an international uniformity of enzyme standards and assay methods, which would allow physicians and clinicians to unambiguously compare the potencies of commercially available enzyme products. 

The last part brings together a completely updated and elaborate description of the methods of assay of pharmaceutical enzymes, reflecting the output of sustained collaborative work between universities and industries in the framework of the Commission on Pharmaceutical Enzymes of the Fdddration International Pharmaceutique during the last two decades. 

Enzyme activity is expressed in units of activity. The Enzyme Commission of the International Union of Biochemistry recommends to express it in international units (lU), defining 1 lU as the amount of an enzyme that catalyzes the transformation of 1 pmol of substrate per minute under standard conditions of temperature, optimal pH, and optimal substrate concentration (International Union of Biochemistry). Later on, in 1972, the Commission on Biochemical Nomenclature recommended that, in order to adhere to SI units, reaction rates should be expressed in moles per second and the katal was proposed as the new unit of enzyme activity, defining it as the catalytic activity that will raise the rate of reaction by 1 mol/second in a specified assay system (Anonymous 1979). This latter definition, although recommended, has some practical drawbacks. The magnitude of the katal is so big that usual enzyme activities expressed in katals are extremely small numbers that are hard to appreciate the definition, on the other hand, is rather vague with respect to the conditions in which the assay should be performed. In practice, even though in some journals the use of the katal is mandatory, there is reluctance to use it and the former lU is still more widely used. 

Enzyme classification is primarily based on the recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (lUBMB)", and it describes each type of characterized enzyme for which an EC (Enzyme Commission) number has been provided. EC classes define enzyme function based on the reaction, which is catalyzed by the enzyme. The classification scheme is hierarchical, with four levels. There are six broad categories of function at the top of this hierarchy and about 3500 specific reaction types at the bottom. EC classes are expressed... 

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