The Inhibitory Effect of Heme on Heme Formation In Vivo: Possible Mechanism for the Regulation of Hemoglobin Synthesis

摘要

1) The effect of hemin on heme synthesis was studied in vivo. Heme synthesis was measured by determining red cell ⁵⁹Fe uptake and glycine-2-¹⁴C incorporation into red cell hemin in normal CF1 female mice.2) Both bovine and human hemin significantly decreased red cell ⁵⁹Fe uptake 48, 72, and 96 hours after hemin injection.3) Glycine-2-¹⁴C incorporation into red cell hemin was decreased to 50% of control values after the administration of hemin (90 μmoles 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 ⁵⁹Fe uptake by 64%.6) There was no measurable effect of δ-aminolevulinic acid on hemin inhibition of red cell ⁵⁹Fe 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.