The regulation of mineral absorption in the gastrointestinal tract.
The absorption of metal ions in the mammalian single-stomached gut is fortunately highly selective, and both luminal and tissue regulation occur. Initially, assimilation of metal ions in an available form is facilitated by the intestinal secretions, chiefly soluble mucus (mucin) that retards hydrolysis of ions such as Cu, Fe and Zn. Metal ions then bind and traverse the mucosally-adherent mucus layer with an efficiency M+ > M2+ > M3+. At the mucosa Fe3+ is probably uniquely reduced to Fe2+, and all divalent cations (including Fe2+) are transported by a membrane protein (such as divalent cation transporter 1) into the cell. This minimizes absorption of toxic trivalent metals (e.g. Al3+). Intracellular metal-binding molecules (such as mobilferrin) may be present at the intracellular side of the apical membrane, anchored to a transmembrane protein such as an integrin complex. This mobilferrin would receive the metal ion from divalent cation transporter 1 and, with part of the integrin molecule, transport the metal to the cytosol for safe sequestration in a larger complex such as ferritin or 'paraferritin'. beta 2-Microglobulin and HFE (previously termed human leucocyte antigen H) may be involved in stabilizing metal mobilferrin-integrin to form this latter complex. Finally, a systemic metal-binding protein such as transferrin may enter the antiluminal (basolateral) side of the cell for binding of the sequestered metal ion and delivery to the circulation. Regulatory proteins, such as HFE, may determine the degree of ion transport from intestinal cells to the circulation. Gradients in pH and perhaps pCa or even pNa could allow the switching of ions between the different transporters throughout this mechanism.
Powell
J J
JJ
Gastrointestinal Laboratory, Rayne Institute, St Thomas' Hospital, London, UK. jonpowel@ucdavis.edu
Jugdaohsingh
R
R
Thompson
R P
RP
D000535:Aluminum / Q000493:pharmacokinetics; D004064:Digestive System / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000493:pharmacokinetics; D008903:Minerals / Q000493:pharmacokinetics*; D009093:Mucus / Q000378:metabolism; D015032:Zinc / Q000493:pharmacokinetics
D008903:Minerals; D000535:Aluminum; D007501:Iron; D015032:Zinc