title: Acquisition of iron from transferrin regulates reticulocyte heme synthesis.
abstract: Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up 59Fe from [59Fe]SIH and incorporate it into heme to a much greater extent than from saturating concentrations of [59Fe]transferrin. Also, Fe-SIH stimulates [2-14C]glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate 59Fe incorporation into heme from either [59Fe]transferrin or [59Fe]SIH but does reverse the inhibition of 59Fe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes.
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D005998:Glycine / Q000097:blood; D006418:Heme / Q000096:biosynthesis*; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000097:blood; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D007502:Iron Chelating Agents; D014168:Transferrin; C049137:salinazid; D006418:Heme; D000622:Aminolevulinic Acid; D007501:Iron; D005998:Glycine; D007538:Isoniazid