Regulation of Iron Entry into Reticulocytes. I. Feedback Inhibitory Effect of Heme on Iron Entry into Reticulocytes and on Heme Synthesis

Abstract

Abstract In the presence of hemin 59Fe incorporation into both heme and reticulocytes decreases. Isonicotinic acid hydrazide which inhibits heme synthesis in vitro is shown to increase reticulocyte radioiron uptake. During inhibition of globin synthesis by cycloheximide, reticulocyte radioiron uptake decreases. This decrease is probably caused by free heme which accumulates in reticulocytes after inhibition of globin synthesis. Simultaneous addition of an inhibitor of heme synthesis—isonicotinic acid hydrazide—to reticulocytes treated by cycloheximide decreases the inhibitory effect of this antibiotic on the iron entry into reticulocytes. The authors suppose the feedback linkage by which heme regulates iron entry into reticulocytes.