Acylphosphatase possesses nucleoside triphosphatase and nucleoside diphosphatase activities

Abstract

We have demonstrated that acylphosphatase possesses ATP-diphosphohydrolase (apyrase-like) activity. In fact, acylphosphatase first catalyses the hydrolysis of the γ-phosphate group of nucleoside triphosphates, and then attacks the β-phosphate group of the initially produced nucleoside diphosphates, generating nucleoside monophosphates. In constrast, it binds nucleoside monophosphates but does not catalyse their hydrolyses. The calculated kcat values for the nucleoside triphosphatase activity of acylphosphatase are of the same order of magnitude as those displayed by certain G-proteins. An acidic environment enhances the apyrase-like activity of acylphosphatase. The true nucleotide substrates of acylphosphatase are free nucleoside di- and triphosphates, as indicated by the Mg2+ ion inhibition of the activity. We have also demonstrated that, although nucleoside triphosphates are still hydrolysed at pH 7.2 and 37 °C, in the presence of millimolar Mg2+ concentrations this occurs at a lower rate. Taken together with the previously observed strong increase of acylphosphatase levels during induced cell differentiation, our findings suggest that acylphosphatase plays an active role in the differentiation process (as well as in other processes, such as apoptosis) by modulating the ratio between the cellular levels of nucleoside diphosphates and nucleoside triphosphates.