title: The ferrireductase paraferritin contains divalent metal transporter as well as mobilferrin.
abstract: Inorganic iron can be transported into cells in the absence of transferrin. Ferric iron enters cells utilizing an integrin-mobilferrin-paraferritin pathway, whereas ferrous iron uptake is facilitated by divalent metal transporter-1 (DMT-1). Immunoprecipitation studies using antimobilferrin antibody precipitated the previously described large-molecular-weight protein complex named paraferritin. It was previously shown that paraferritin functions as an intracellular ferrireductase, reducing ferric iron to ferrous iron utilizing NADPH as the energy source. It functions in the pathway for the cellular uptake of ferric iron. This multipeptide protein contains a number of active peptides, including the ferric iron binding protein mobilferrin and a flavin monooxygenase. The immunoprecipitates and purified preparations of paraferritin also contained DMT-1. This identifies DMT-1 as one of the peptides constituting the paraferritin complex. Since paraferritin functions to reduce newly transported ferric iron to ferrous iron and DMT-1 can transport ferrous iron, these findings suggest a role for DMT-1 in conveyance of iron from paraferritin to ferrochelatase, the enzyme utilizing ferrous iron for the synthesis of heme in the mitochondrion.
authors.affiliation: University of South Alabama Cancer Center, Mobile, Alabama 36688, USA. jumbreit@usamail.usouthal.edu
authors.forename: Jay N
authors.initials: JN
authors.lastname: Umbreit
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Conrad
authors.forename: Lucille N
authors.initials: LN
authors.lastname: Hainsworth
authors.forename: Marcia
authors.initials: M
authors.lastname: Simovich
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis* / Q000737:chemistry; D027682:Cation Transport Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D038181:FMN Reductase; D005290:Ferric Compounds / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry*; D005296:Ferrous Compounds / Q000378:metabolism; D006801:Humans; D007163:Immunosorbent Techniques; D033862:Iron-Binding Proteins; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D038181:FMN Reductase; D005290:Ferric Compounds; D005293:Ferritins; D005296:Ferrous Compounds; D033862:Iron-Binding Proteins; D009247:NADH, NADPH Oxidoreductases; D009249:NADP; D000099236:Solute Carrier Family 11, Member 2; C085511:mobilferrin; C023903:ferric citrate iron reductase