The major iron-bearing cytosol components of human reticulocytes identified after incubation with 59 Fe-125I-transferrin have been studied further. Component C previously found to behave consistently as an intermediate in the iron transport pathway to haem is shown to consist entirely of ferritin. After a short pulse of labelled transferrin incubation, chase experiments showed a fall of ferritin label with time and a corresponding increase in haemoglobin-iron incorporation. There was no loss of ferritin to the culture medium. Restriction of iron uptake by reticulocytes using both p-hydroxymercuribenzoate inhibition of uptake and incubation with progressively lower saturations of iron-transferrin gave linearly related incorporation of 59Fe into ferritin and haemoglobin at all levels of iron uptake, thus negating the concept of ferritin as an 'overspill' form of reticulocyte iron. The results suggest that cytosol ferritin is an obligatory intermediate in reticulocyte iron transport.
1. A method is described by which substances inhibiting caeruloplasmin oxidase activity directly may be distinguished from those acting on stimulatory contaminant iron or on the product of enzyme action. 2. Many previously reported inhibitors, including saturated aliphatic carboxylates, hydrazines, 1,10-phenanthroline, borate and various psycho-active drugs, are found either not to act on the enzyme or to inhibit it only weakly. 3. A series of inorganic anions are compared as inhibitors. Anions such as azide and cyanide with strong copper-binding properties are the most effective inhibitors. There is a general inverse relationship between anion size and inhibitory power. Iodide is anomalous, the order of effectiveness of halides being F(-)>I(-)[unk]Cl(-)>Br(-). 4. Multidentate copperchelating ligands have little inhibitory effect. 5. A group of substances containing the structural unit [unk]C=[unk].CO(2)H, including fumarate and benzoate, cause inhibition. 6. Relative inhibitions by a series of mono-substituted benzoates are inversely related to molecular size. 7. Results are discussed in relation to earlier work on the disposition and function of the copper atoms of caeruloplasmin.
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