Regulation of Histidine Uptake by Specific Feedback Inhibition of Two Histidine Permeases in Saccharomyces cerevisiae

Although a large fraction of the histidine accumulated from the medium remains free and intact in Saccharomyces cerevisiae, it is not exchangeable with external histidine. Hence, the steady state concentration level of histidine is not determined by a balance between rates of inflow and outflow. Preloading the cells with histidine results in a rapid inhibition of histidine uptake, whereas preloading with other amino acids has no effect on histidine uptake. The inhibition by internal histidine affects the activity, and not the synthesis, of two specific histidine permeases. The histidine permease with high affinity for histidine is much more sensitive to this inhibition than the second histidine permease. A mutant (his‐p1) specifically affected in histidine uptake was isolated. Criteria for demonstrating that a mutation or a feedback control directly affect an uptake system are discussed. It is concluded that the his‐p1 mutant is histidine‐permease‐less, and that the activity of the histidine permeases are regulated by specific feedback inhibition.