The human glutathione S-transferases: a study of the tissue distribution, genetic variation and development of the GST1, GST2 and GST3 isoenzymes

The glutathione S-transferases are a group of detoxicating enzymes found in all human tissues studied. They are believed to be the products of at least three autosomal gene loci (GST1, GST2 and GST3). The expression of these loci was examined using starch-gel electrophoresis and chromatofocusing and shown to demonstrate tissuespecific patterns. Genetic variation was observed at the GST1 locus and data from hybridisation studies supported the suggestion that this locus is polymorphic in humans. The expression of the GST2 isoenzymes was more complex and data from starch-gel electrophoresis and chromatofocusing was harder to interpret. The expression of the GST2 isoenzymes, unlike that of the GST1, was not a constant characteristic in different tissues from the same individual and a previous proposal that this locus is also polymorphic was not supported since the population data failed to achieve Hardy-Weinberg equilibrium. Since further hybridisation studies of GST2 isoenzymes demonstrated that some of the forms were interconvertable I believe that the various basic isoenzymes arise by a process of post-translational modification. The GST3 isoenzymes were less intensely investigated and the data revealed no evidence of genetic variability at this locus. Differential expression of the three loci throughout development was studied in four tissues and compared with the expression in corresponding adult tissues. Chromatofocusing was used to quantify the products of the three loci at different developmental ages so that the relative expressions of the loci could be determined. At least one of the loci demonstrated developmental changes in expression in each of the tissues studied. Tissues of the same embryological origin showed similar developmental expression of GST whereas tissues of different embryological origins revealed marked differences in the ontogeny of the enzyme. No specifically fetal forms of GST were demonstrated. In some tissues GST loci were not fully expressed until about one year post-natal age and these observations are believed to provide biochemical evidence for the theory of neoteny in humans