Inhibition by uranyl nitrate of adenosine triphosphatases derived from animal and human tissues

Abstract

Inhibition of adenosine triphosphatase (ATPase) by uranyl nitrate (UO 2 2+ or U 6+) was studied in microsomal fractions and tissue homogenates of several organs and species. U 6+ inhibited ouabain-sensitive (Na + + K +-dependent) ATPase and ouabain-insensitive (Mg 2+-dependent) ATPase with I50 of 2 × 10 −5 to 2 × 10 −4 m. Higher concentrations of U 6+ were required to inhibit the enzyme in homogenates than in microsomal fractions. Mg 2+ ATPase was somewhat more sensitive to U 6+ than was Na + + K + ATPase when data were corrected for protein content of enzyme preparations. The inhibition of Na + + K + ATPase, but not Mg 2+ ATPase, was markedly antagonized by Na +. This suggests that U 6+ may inhibit Na + + K + ATPase at the Na + site on the enzyme, whereas ouabain inhibits at the K + site. ATP decreased and Mg 2+ increased the inhibition of both enzymes. K + had no effect. The remaining studies were done with Na + + K + ATPase. Increasing pH enhanced inhibition. The enzyme was protected by bovine serum albumin and citric acid. Ascorbic acid increased inhibition possibly by reducing U 6+ to U 4+, thus rendering the new ionic species reactive with sulfhydryl groups in addition to organic anions.