Studies on the quantitative variation of human red cell peptidase A activity

SUMMARY 1. A new method for the assay of peptidase A activity in human red cells and leucocytes is described. 2. Wide variation in the level of red cell peptidase A activity between different individuals with the common electrophoretic phenotype Pep A1 has been demonstrated. 3. Family studies show highly significant parent‐child and sib‐sib correlations, but no significant parent‐parent correlation. The findings indicate that the differences in level of activity between individuals are to a large extent genetically determined. 4. Peptidase A activities in leucocytes show much less variation than in red cells. Only a small correlation, which was not statistically significant was found between red cell and leucocyte activity. In particular the levels of leucocyte peptidase A activity in individuals with very weak red cell activities were found to be very similar to those seen in individuals with strong red cell activity. 5. Weak peptidase A activity in red cells was not found to be associated with weak activity of other red cell peptidases. 6. No evidence for the differential occurrence of inhibitors or activators of peptidase A in red cells of individuals with different levels of activity was obtained in various experiments designed to test this possibility. 7. The electrophoretic patterns seen in individuals heterozygous for certain rare alleles ( Pep A 5 and Pep A 6 ) which determine electrophoretic variants of peptidase A suggest that two different alleles (provisionally called Pep A 1S and Pep A 1W ) determining different forms of the enzyme with the usual electrophoretic mobility (Pep Al), but with different activities in red cells occur. Individuals presumed to be heterozygous for Pep A 5 (or Pep A 6 ) and for Pep A 1S show a symmetrical triple‐banded electrophoretic pattern, which suggests that the activity attributable to Pep A 5 or Pep A 6 is about the same as that attributable to Pep A. 1S . Individuals presumed to be heterozygous for the rare allele Pep A 5 or Pep A 6 and for Pep A 1W show in red cells an asymmetrical electrophoretic pattern with a marked deficiency of activity attributable to Pep A 1W . In leucocytes, however, they show a symmetrical electrophoretic pattern indistinguishable from the patterns observed in individuals with the same rare allele in heterozygous combination with the common allele Pep A S . 8. It is suggested that the wide variation in activity seen in red cells of individuals with the common electrophoretic phenotype Pep A1, is at least in part attributable to alleles ( Pep A 1S and Pep A 1W ) occurring at the same locus as the alleles which determine previously described electrophoretic variants. However, it remains possible that allelic differences at other gene loci and producing their effects in different ways may also contribute to the genetically determined variation in activity.