REGULATORY MECHANISMS OF CELLULAR RESPIRATION : I. THE RÔLE OF CELL MEMBRANES: URANIUM INHIBITION OF CELLULAR RESPIRATION

Uranium as UO(2)(NO(3))(2) combines reversibly with proteins. The degree of dissociation of this combination depends, among other factors, on the H(+) concentration. At pH 7.3 the U-albumin complex was easily dissociated on addition of citrate, while at pH 3.8 it was not. Uranium inhibited reversibly a number of enzyme systems. Uranium enzyme inhibitions could be reversed on addition of certain hydroxypolycarboxylic acids (citric acid, α-hydroxyaspartic acid, malic acid); in no case, however, did phosphate have any effect. In cell-free yeast juice, the fermentation of glucose-hexosediphosphate was inhibited by UO(2)(NO(3))(2). Slight reactivation occurred on addition of phosphate. In living yeast cells, the fermentation and oxidation of glucose was inhibited by small amounts of UO(2)(NO(3))(2) (7,7 micrograms per mg. dry weight), while the oxidation of acetic acid, ethyl alcohol, malic and citric acids, was not affected at all. U inhibition in living yeast cells at pH 7.3 was completely released on addition of small amounts of phosphate, adenosinetriphosphate, and citrate, while at pH 3.8 U inhibition was not released by phosphate and citrate. At saturation, one yeast cell contained 7.06 x 10(6) molecules of uranium. Lactic dehydrogenase was not inhibited by U while the oxidation of lactic acid by gonococci was inhibited. Addition of phosphate released this inhibition. The U inhibition of liver succinoxidase was unaffected by phosphate, while the U inhibition of the oxidation of succinate by E. coli was released by phosphate. It has been concluded from these experiments that U inhibition of cell metabolism is due to combination of the metal with the protein portion of the cell membrane. Uranium is presented as an example of surface inhibition.