A variety of different enzymes and proteins are synthesized in the human body, and the primary amino acid sequence of each of their distinctive polypeptide chains is coded in the DNA of a separate gene locus. Thus there must be large number of so-called "structural" gene loci in the genetic make-up of every individual. In addition, as a result of mutational events there may occur at any given gene locus a series of different alleles each of which determines a structurally distinct form of the particular polypeptide chain. Therefore, the extent to which individual members of a population differ from one another in the structural characteristics of the enzymes and proteins they synthesize will depend on the number of different alleles which are present at these different loci, and on the alternative frequencies with which they occur.

Studies on a variety of different enzymes and proteins have led to the discovery of a large number of structurally variant forms, which are genetically controlled. The inherited variants of different enzymes and proteins, which we find among human populations today, must be attributed to specific gene mutations which occurred in single individuals among our ancestors in earlier generations. Thus, it appears that at almost all loci coding for enzymes and proteins, a large number of different mutant alleles, which may be generated by separate mutations, actually exist between living members of our species.

Although the incidence of the majority of such mutant alleles is low in different human populations, occasionally some occur with an appreciable (≥1%) frequency giving rise to well-known phenomenon of genetic polymorphism - a situation where the individual members of a population are sharply classified into two or more relatively common genetically determined phenotypes due to the occurrence of two or more alleles at a particular locus.

Enzyme Polymorphisms
The concept of enzyme polymorphism is based on the occurrence of variant forms of an enzyme controlled by two or more alleles in frequencies exceeding 1%. Enzyme variants may originate from duplications and deletions of the genetic material, but most mutations leading to amino acid substitutions, which depend upon the type of substitution, may cause alterations in the electric charge, kinetic properties, and rate of synthesis or stability of the enzyme. Markert and Moller (1959) coined the term isozyme or isoenzyme to describe the existence of different molecular forms of an enzyme, which catalyzed the same biochemical reaction, but differ in their electrophoretic properties.

The technique most commonly used to detect enzyme polymorphisms is electrophoresis in starch gels, although agarose and polyacrylamide are also suitable gel media. The amount of material (usually blood) required is small and technique is convenient for screening a large number of samples in a relatively short time period.

The electrophoretic enzyme pattern in homozygous individuals usually show one major zone of enzyme activity, which may be accompanied by minor zones of secondary isozymes. Such patterns in heterozygous individuals may, however, show different degrees of complexity i.e., it shows one or more components which are not present in either homozygote. These extra enzyme components found only in heterozygous are referred to as "hybrid enzymes" and show an electrophoretic mobility intermediate to those of the parental homozygote enzymes. In the case of a dimer, trimer and tetramer enzyme, there will be a triple, four and five banded pattern, respectively. In each case the outermost bands correspond to the two parental homozygotes, and the band with intermediate motilities represent the "hybrid enzymes".

Since most of the enzyme polymorphisms were discovered by electrophoresis, it is important to mention that although an electrophoretic difference indicates a difference in structure between the polymorphic forms of an enzyme, it does not in general provide information about possible functional differences, if any.

During the last three decades, a large number of different human enzymes have been investigated for electrophoretic variants in a variety of different populations. To obtain an overview of the incidence of the phenomenon, Harris et al. 1977 observed that of the 104 different loci coding for enzymes that had been screened, 33 had been found to exhibit an electrophoretically detectable polymorphism. In other words, one out of every three human loci coding for enzymes is polymorphic.

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