Characteristics of iron(III) uptake by isolated fragments of rat small intestine in the presence of the hydroxypyrones, maltol and ethyl maltol.
Accumulation of radioactive iron (59Fe) into isolated fragments of rat small intestine in the presence of two hydroxypyrones, maltol and ethyl maltol, was compared with that in the presence of another chelator of iron(III), nitrilotriacetic acid (NTA). The characteristics of uptake were similar with all three ligands. Between 10(-6) and 10(-4) M, iron uptake showed saturable kinetics. The uptake was partially inhibited by metabolic inhibitors. Above 10(-4) M a non-saturable uptake, unaffected by metabolic inhibitors became evident in the presence of the pyrones. The distribution of 59Fe after uptake was determined by gel filtration. At low iron concentrations (10(-6) M), 35-40% of absorbed iron was associated with proteins of molecular weights similar to those of ferritin and transferrin. At high concentrations (10(-3) M), the majority of 59Fe was found in a low molecular weight fraction. At each concentration, a small amount of 59Fe was bound to a membrane fraction. 5% Polyethylene glycol, which reduces glycocalyx viscosity enhanced uptake at low iron concentrations (10(-6) M) but did not affect the non-saturable diffusion seen at higher concentrations (10(-3) M). The iron(II) chelator, bathophenanthroline sulphonate (10(-3) M), decreased uptake at low iron concentrations but did not affect the non-saturable uptake. It is suggested that conversion of iron(III) to iron(II) may take place at the mucosal cell surface before uptake via the saturable system. Apparent Km values for iron uptake via the saturable system were higher in the presence of maltol and ethyl maltol than in the presence of NTA, presumably since the iron binds more avidly to the hydroxypyrones and so is less readily donated. Excess ligand, either pyrone or NTA, reduced the rate at which 59Fe was donated to the uptake system. The Vmax value for uptake from the pyrones was greater than from NTA. It is concluded that maltol, ethyl maltol and NTA can hold iron(III) in solution and donate it to an endogenous uptake system. But, the hydroxypyrones may be more suitable ligands for the oral administration of iron since, when complexed with iron, they lack the toxic effects associated with iron(III)-NTA and with iron(II) preparations.
Levey
J A
JA
Department of Chemistry, University of Essex, Colchester, U.K.
Barrand
M A
MA
Callingham
B A
BA
Hider
R C
RC
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D007501:Iron / Q000493:pharmacokinetics*; D008297:Male; D009571:Nitrilotriacetic Acid / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002614:Chelating Agents; D011714:Pyrans; D011753:Pyrones; C008316:maltol; D011092:Polyethylene Glycols; D007501:Iron; D009571:Nitrilotriacetic Acid; C052408:ethyl maltol