Paraferritin:  A Protein Complex with Ferrireductase Activity Is Associated with Iron Absorption in Rats

Abstract

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.

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

“…been shown to be a part of the paraferritin complex [35]. The control of localization of mobilferrin to the membrane and to the mucin carbohydrate chains is a matter of speculation at this time.…”

Cellular location of proteins related to iron absorption and transport

“…onstrated in the cytoplasm by b 3 integrin (CD61). This may be explained by previous demonstration of cytosolic b 3 integrin in association with a large protein complex [8]. Hephaestin showed a rather uniform distribution of cytoplasmic¯uorescent staining.…”

“…Loss of KDEL probably permits mobilferrin to bind the a subunit of integrin on the surface membrane. Both mobilferrin and b 3 integrin can be isolated from cellular cytoplasm as constituents of a large protein complex named paraferritin, which also contains¯avin monooxygenase and b 2 microglobulin [2,8]. The association of mobilferrin/calreticulin with MHC class I molecules, the development of iron overloading in b 2 microglobulin knockout mice, and the occurrence of sideroblastic anemia in patients with¯avin monooxygenase (a ferrireductase) de®-ciency and increased mobilferrin suggest an association with hemochromatosis and the iron-overloading disorders [26À30].…”

Demi̇r Metaboli̇zmasinda, Demi̇r Eksi̇kli̇ği̇nde Ve Demi̇r Fazlaliğinda Yeni̇li̇kler

“…Emilim yeri duedonum ve üst jejunum olan demirin organizmada, farklı fonksiyonlara yönelen farklı formlarının hücrelere giriş için seçtiği yolların ela farklı olduğu gösterilmiştir (9).…”

“…Yüksek konsantrasyonda diferrik transferrin varlı-ğında, TRIP daha önemli hale gelir. Bu yolun önemi henüz tam bilinmektedir (9) Demir ayrıca hücrelere, protopofirin şelatı şeklinde de taşınır (4.yol). Bu yolun substratı hem demiridir.…”