Effect of Ascorbic Acid Administration on Serum Concentration of Transferrin Receptors

Since Szent-Gyorgyi first purified ascorbic acid (vitamin C) in 1928 (1), a number of associations between ascorbic acid and iron metabolism have been described. At the molecular level, ascorbic acid mobilizes iron from the crystal core of ferritin in vitro by reducing Fe3 to Fe2 (2). Intracellularly, ascorbic acid enhances iron-induced translation of ferritin (3) by favoring the conversion of the iron regulatory protein (IRP) from the RNA binding form to aconitase (3). Ascorbic acid also retards degradation of ferritin by blocking lysosomal autophagy of ferritin and transformation to hemosiderin (4)(5). In humans, the oral administration of ascorbic acid enhances the absorption of non-heme iron from the diet (6) and leads to increases in serum iron in subjects with iron overload and ascorbic acid deficiency (7). Moreover, iron overload states are associated with reduced ascorbic acid concentrations, possibly because of increased catabolism of ascorbic acid (7)(8).The amount of labile iron in the cytosol influences the stability of transferrin receptor mRNA and the translation of ferritin mRNA (9)(10)(11). Posttranscriptional regulation occurs by means of an interaction between IRPs, proteins that sense changes in the chelatable intracellular iron pool, and iron-responsive elements located on untranslated regions of transferrin receptor mRNA and ferritin mRNA (12)(13)(14). In states of iron abundance, an IRP has aconitase activity and does not bind to iron-responsive elements, producing increased transferrin receptor mRNA degradation and increased ferritin mRNA translation. Conversely, when iron is deficient, an IRP loses aconitase activity and binds to iron-responsive elements, causing increased transferrin receptor mRNA stability and a repression of ferritin mRNA translation (15)(16). Thus, intracellularly, the presence of iron leads to inhibition of transferrin receptor expression and promotion of higher ferritin expression, whereas the deprivation of …