PEDIATRICS Vol. 37 No. 1 January 1966, pp. 120-131
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ISOZYMES: BIOLOGICAL AND CLINICAL SIGNIFICANCE

William H. Zinkham M.D.1, Antonio Blanco M.D.1, and Luba Kupchyk A.B.1

1 Department of Pediatrics of The Johns Hopkins University School of Medicine and the Harriet Lane Service of The Johns Hopkins Children's Medical and Surgical Center, Baltimore, Maryland

A RECENT and rather surprising discovery in biochemistry was the finding that a single enzyme can exist in several different forms within a single tissue. This discovery not only led to the development of new information concerning the nature of enzymes and enzyme action, but also has contributed to our knowledge of enzyme changes in disease. The purpose of this brief review is to describe the methodology used to recognize the different forms of an enzyme; to indicate the general biological significance of the phenomenon, and in particular, to focus on those areas which have broadened our understanding of the metabolic changes accompanying growth and development; and finally, to present data obtained from the clinical application of enzyme heterogeneity to medical diagnosis.

DEFINITION OF ISOZYMES

Over the years a major objective of the enzymologists has been to prepare enzymes in pure crystalline form. Once this had been accomplished, it was assumed that all of the molecules in the preparation were alike in regards to size, shape, amino acid composition, and the substances (substrates) on which they acted. Enzymes are proteins, and when newer techniques for separating proteins were applied to some of the crystalline enzyme preparations, a heterogeneous population of molecules with the same substrate specificity was discovered. This and other observations suggested to Markert and Møller that the classification of enzymes based on substrate specificity alone would have to be extended. For this reason they proposed the term isozyme to describe the different molecular forms in which proteins with the same enzymatic specificity may exist" within single organism. The most extensively studied enzyme from the point of view of molecular heterogeneity is lactate dehydrogenase (LDH).