Paraferritin: a protein complex with ferrireductase activity is associated with iron absorption in rats.
Recent studies reported that iron salts were absorbed in the duodenum utilizing a pathway involving membrane-associated integrin and a cytosolic protein named mobilferrin. In addition, a large molecular weight cytoplasmic complex was labeled with radioiron during mucosal uptake of iron in the duodenum. The molecular mass of this protein was 520 000 daltons, slightly larger than ferritin. On denaturing SDS-PAGE, the purified protein complex appeared to consist of at least four polypeptides, closely associated with each other. This complex was called paraferritin because its hydrodynamic volume resembled ferritin. In the present work, antibody studies demonstrate the presence of integrin, mobilferrin, and flavin monooxygenase in the water-soluble complex. Biochemical studies demonstrate the presence of a NADPH-dependent flavin monooxygenase ferrireductase activity that reduces Fe(III) to Fe(II). Antibodies against either integrin or mobilferrin inhibit monooxygenase activity. Inhibition of monooxygenase activity decreases radioiron uptake by tissue culture intestinal cells. Thus, we postulated that paraferritin plays a role in the mucosal uptake and transport of inorganic iron in small intestinal absorptive cells and is a mechanism for both the internalization of integrin from membranes to cellular cytosol and the delivery of iron to cellular constituents in an appropriate redox state.
Umbreit
J N
JN
Division of Hematology/Oncology, University of South Alabama, Mobile 36688, USA.
Conrad
M E
ME
Moore
E G
EG
Desai
M P
MP
Turrens
J
J
D000818:Animals; D000906:Antibodies; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038181:FMN Reductase; D005293:Ferritins / Q000737:chemistry / Q000378:metabolism*; D005415:Flavins / Q000032:analysis; D066298:In Vitro Techniques; D016023:Integrins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010624:Phenelzine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005415:Flavins; D016023:Integrins; D033862:Iron-Binding Proteins; D046911:Macromolecular Substances; C085511:mobilferrin; D005293:Ferritins; D007501:Iron; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase; D010624:Phenelzine