Studies of the Effect of Sulphydryl and Other Inhibitors on Reticulocyte Uptake of Doubly‐labelled Transferrin

S ummary . Inhibition of iron uptake from transferrin by reticulocytes has been further studied using doubly‐labelled 59 Fe‐ 125 I‐transferrin. The inhibition by p ‐hydroxy mercuribenzoate, previously reported, is shown to occur also with the sulphydryl inhibitors p ‐hydroxymercuriphenylsulphonate and N‐ethylmaleimide. The pattern of ‐SH inhibition is compared with and found to differ from that for two other inhibitors, trypsin, which alters membrane binding, and sodium fluoride, a metabolic inhibitor. When assessed by three variables, namely the effect of inhibitor concentration, the time of inhibitor exposure, and the effect on the rate of uptake, sulphydryl inhibitors are shown to act differentially on transferrin binding and on iron uptake. The latter is far more sensitive and is affected at lower concentrations. It is concluded that ‐SH groups are active in the dissociation of iron from its transferrin bond after surface binding has occurred. The effect of‐SH inhibitors on transferrin binding may be secondary to changes in membrane function induced by higher concentrations of these inhibitors.