The Affinity of Human Erythrocyte Porphobilinogen Synthase for Zn2+ and Pb2+

Abstract

Porphobilinogen synthase activity has been measured in human erythrocyte lysates supplemented with metal‐ion buffers to control free Zn2+ and Pb2+ concentrations. The enzyme is activated by Zn2+ with a Km, of 1.6 pM and inhibited by Pb2+ with a K1 of 0.07 pM. Pb2+ and Zn2+ appear to compete for a single metal‐binding site. The half‐time for loss of Zn2+ from the active site, or replacement of Pb2+ by Zn2+, were in the 10–20‐min range at 37°C. Zn2+ did not affect the affinity for the substrate 5‐aminolevulinate, but Pb2+ reduced it non‐competitively. All the experiments were conducted with a blood sample of the common 1–1 phenotype [Astrin, K. H., Bishop, D. P., Wetmur, J. G., Kaul, B., Davidow, B. & Desnick, R. J. (1987) Ann. NY Acad. Sci. 514, 23–29] Copyright © 1995, Wiley Blackwell. All rights reserved