Inhibitory characteristics of cadmium, lead, and mercury in human sodium and potassium dependent adenosinetriphosphatase preparations
Nechay, B.R.; Saunders, J.P.
Journal of Environmental Pathology and Toxicology 2(2): 283-290
1978
ISSN/ISBN: 0146-4779 PMID: 216761 Document Number: 137221
Inhibition of ATPase by bichlorides of Cd, Pb and Hg was studied in microsomal fractions and homogenates of human kidney. HgCl2 was most potent inhibitor of Na+ + K+ ATPase activity (l50 [50% inhibition] 1-6 .times. 10-6 M), but the tissue homogenates contained protective substances which reduced the effectiveness of the metal. Tissue homogenates did not protect the enzyme from inhibition by CdCl2 (l50, 1.4 .times. 10-4 M) or PbCl2 (l50 6 to 8 .times. 10-5 M). Mg2+ ATPase, which contaminated the enzyme preparations, was 10-fold more resistant to Cd and about 100-fold more resistant to Pb than Na+ + K+ ATPase. Hg was about equally effective as an inhibitor of both Na+ + K+ ATPase and Mg2+ ATPase. The following studies on the mechanisms of inhibition refer to Na+ + K+ ATPase. Inhibition by Cd had irreversible, and by Pb reversible, characteristics. Because of protective factors present in the kidney, the nature of inhibition was not determined for Hg. Increasing Na+ concentration reduced effectiveness of Pb and Hg; it did not alter the inhibition by Cd. Changing K+ concentration did not modify inhibition by either of the metals. ATP or MgATP protected the enzyme from inhibition by Pb but not Cd or Hg. Mg2+ increased the inhibitory effect of Pb but did not change the effects of Cd or Hg. The mechanisms of Na+ + K+ ATPase inhibition are unique for each metal, based on different inhibitory characteristics. Pb may interact with the enzyme at Na and phosphate sites and may chelate ATP. Hg may act competitively with Na. The binding of Cd to the enzyme is uninfluenced by different components necessary for the enzyme activity.