Isoenzymes, concepts

The impact of the isoenzyme concept is first beginning to be felt in... 

This concept has led to market isoenzyme selective inhibitors, that is, monoamine oxidase (MAO) inhibitors (moclobemide for MAO-A as an antidepressive drug, selegiline for MAO-B in Parkinson disease), selective inhibitors for various cyclic nucleotide phosphodiesterases (sildenafil for PDE5), and selective cyclooxygenase inhibitors (celecoxib for cox2). 

Finasteride and dutasteride are both mechanism-based inhibitors of type 1 and type 2 5a-reductase isoenzymes that inactivate 5a-reductase by an apparent irreversible modification of 5o-reductase (105,106). The inhibition constants (median inhibitory concentrations [ICsos]) in Table 45.5 suggest that finasteride is 30 times more selective for type 2 5a-reductase, whereas dutasteride appears to be approximately 10 times more potent as an inhibitor of type 2 5a-reductase than as a inhibitor of type 1 5a-reductase. The reduction of finasteride to dihydrofinasteride proceeds through an enzyme-bound, NADP-dihydrofinasteride adduct (see Chapter 5) (105). The mechanism- based inhibition explains the exceptional potency and specificity of finasteride and dutasteride in the treatment of BPH. This concept of mechanism-based inhibition may have application to the development of other inhibitors of pyridine nucleotide-linked enzymes. 

Chapter I. Introduction, historical, general concepts, isoenzymes by E. C. Webb (Brisbane, Queensland)... 

Initially, the concept of isoenzymes had only an operational character (Markert, 1968). Isoenzymes (isozymes) were considered to be any multiple fraction of the same enzyme (Shaw, 1969 Serov, 1968). But later, with the collection of various experimental data, this concept acquired a genetic meaning, and after this the concept of isozymes was given to the genetically determined variants of the same enzyme in the same organisms, as characterized by their similar substrate specificity. The Nomenclature of Multiple Forms of Enzymes, 1971) Enzyme fractions which were not genetically determined were termed multiple forms of enzymes. 

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