Levels of delta-aminolevulinate dehydratase, uroporphyrinogen-I synthase, and protoporphyrin IX in erythrocytes from anemic mutant mice.

Levels of erythrocyte delta-aminolevulinate dehydratase [ALA-dehydratase; porphobilinogen synthase; 5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2.1.24], UROPORPHYRINOGEN-I synthase [Uro-synthase; porphobilinogen ammonia-lyase (polymerizing), EC 4.3;1.8], AND PROTOPORPHYRIN IX (Proto) were measured by sensitive semimicroassays using 2-5 mul of whole blood obtained from normal and anemic mutant mice. The levels of erythrocyte ALA-dehydratase and Uro-synthase showed marked developmental changes and ALA-dehydratase was influenced by the Lv gene. Mice with overt hemolytic diseases (ja/ja, sph/sph, nb/nb, ha/ha) had 10- to 20-fold increases in ALA-dehydratase, Uro-synthase, and Proto compared with their normal controls. Mice with an iron deficiency (mk/mk) and mice with hypoplastic anemias (W/Wv, Sl/Sld, an/an) had mild to moderate increases in these parameters. Elevated enzyme activities and Proto correlated well with the number of reticulocytes. Because all mice with anemias possessed elevated levels of ALA-dehydratase, Uro-synthase, and Proto independent of differences in their genotypes, the increase in these parameters is not likely to be the result of a specific gene defect. The increased enzyme activities and Proto concentration probably reflect increased frequency of young red cells that are still active in heme biosynthesis.