EFFECT OF METABOLIC INHIBITORS ON TRANSFERRIN AND IRON UPTAKE AND TRANSFERRIN RELEASE FROM RETICULOCYTES

Metabolic inhibitors were broadly classified into three groups on the basis of their effect on the uptake of [125I]transferrin and 59Fe and the release of [125I]transferrin by rabbit reticulocytes in vitro: 1. 1. Inhibitors which had no effect on transferrin or iron uptake (sodium malonate and ouabain). 2. 2. Those which blocked iron uptake more than transferrin uptake (retonone, 2,4-dinitrophenol, oligomycin, NaCN, NaN3, NaF and cycloheximide). The effect of these compounds was attributed to inhibition of the mitochondrial electron transfer chain. 3. 3. Those which inhibited iron and transferrin uptake to approximately the same degree (sodium arsenite, iodoacetamide, N-ethylmaleimide, p-chloromercuribenzoate (PCMB), p-chloromercuribenzenesulfonate (PCMBS) and lead acetate). The onset of inhibition by all the inhibitors studied was immediate, but the effects of iodoacetamide, N-ethylmaleimide, PCMB and PCMBS were largely prevented by prior addition of cysteine in 1-4 times the molar concentration of inhibitor. Sodium arsenite, iodoacetamide and N-ethylmaleimide also inhbited transferrin release. These compounds (all sulfhydryl reagents) may act by altering reticulocyte membrane structure, reducing transferrin and hence iron uptake. © 1969.