The mechanism by which inorganic phosphate regulates the level of alkaline phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.1) in rat kidney has been investigated: changes in the level of inorganic phosphate in the renal cell were produced by dietary treatment. The regulatory effect appears to be specific. Out of 10 enzymes studied only alkaline phosphatase increases when phosphate decreases. The decrease in the level of phosphate, under our conditions, is not accompanied by a general change in the pattern of phosphorylated metabolites. The regulation by phosphate is abolished by inhibitors of protein or nucleic acid synthesis. These features of the regulatory system are consistent with a mechanism of genic repression, that could be fundamentally similar to that described for Escherichia coli. The above conclusion has been confirmed by studying the time course of derepression and repression of alkaline phosphatase by following successive changes in phosphate level in the kidney. The half-life of enzyme breakdown during repression was found to be 0.9 day, and this value corresponds (in the same order of magnitude) with the known half-lives for other proteins of the rat.
Read full abstract