The inhibitory effect of heme on heme formation in vivo: possible mechanism for the regulation of hemoglobin synthesis.

1. The effect of hemin on heme synthesis was studied in vivo. Heme synthesis was measured by determining red cell (59)Fe uptake and glycine-2-(14)C incorporation into red cell hemin in normal CF(1) female mice.2) Both bovine and human hemin significantly decreased red cell (59)Fe uptake 48, 72, and 96 hours after hemin injection.3) Glycine-2-(14)C incorporation into red cell hemin was decreased to 50% of control values after the administration of hemin (90 mumoles per kg).4) There was no significant difference between the plasma iron of mice injected with hemin and the values in control groups.5) Protoporphyrin decreased the inhibitory effect of hemin on red cell (59)Fe uptake by 64%.6) There was no measurable effect of delta-aminolevulinic acid on hemin inhibition of red cell (59)Fe uptake.7) Data are presented to show that the effect of hemin is not by a dilution mechanism nor by a decrease in red cell maturation and subsequent release of reticulocytes into the peripheral blood. The findings are discussed in regard to the possible site of a negative feedback control of heme synthesis by heme.