The regulatory role of exogenous hemin in the heme synthetic pathway was studied in fetal mouse liver erythroblasts in culture. Hemin added to culture medium of 13th day embryo liver cells inhibited, dose dependently, the incorporation of the porphyrin precursors, 59Fe, 14C-2-glycine and 14C-5-aminolevulinic acid (ALA) by 85%, 70% and 4%, respectively. This suggests a multiple effect o hemin on the prophyrin biosynthetic enzymes. Exogenous ALA competed with 14C-2-glycine as a prophyrin precursor, but the rate of heme synthesis, measured by 59Fe incorporation, remained unaltered. Protoporphyrin mimicked the hemin effect on the inhibition of glycine incorporation into heme, but reduced iron incorporation by only 20%. Erythroblasts, with an inhibited prophyrin biosynthesis, utilized exogenous 59Fe-hemin for hemoglobin assembly and maintained an undecreased level of hemoglobin synthesis. The results indicate that hemin inhibits the porphyrin biosynthesis in fetal mouse liver erythroblasts mainly at the iron incorporation stage.
|Number of pages||6|
|State||Published - 1979|