Dinucleoside polyphosphate hydrolase

Dinucleoside polyphosphate hydrolase refers to a group of enzymes responsible for the hydrolysis of dinucleoside polyphosphates, such as diadenosine tetraphosphate (Ap4A), diadenosine triphosphate (Ap3A), and related molecules[1][7]. These enzymes, which include members of the Nudix hydrolase family (e.g., human Ap4A hydrolase, bacterial ApaH), cleave the polyphosphate chain connecting two nucleosides, yielding mononucleotides or shorter polyphosphates. The enzymatic breakdown of dinucleoside polyphosphates helps regulate their intracellular and extracellular concentrations, influencing cellular processes such as stress response, DNA replication, gene expression, and signal transduction (notably purinergic signaling)[2][4][6][8]. The most studied substrate is Ap4A, which accumulates under stress and is proposed to act as an alarmone or secondary messenger. Dysregulation of dinucleoside polyphosphate metabolism has been linked to cancer, cardiovascular diseases, and neurodegeneration, though the specific pathological mechanisms are still being elucidated[2][6][4]. While dinucleoside polyphosphate hydrolase is a well-established enzyme class, knowledge about its utility as a direct therapeutic target is still evolving. Its physiological substrates and disease links are best defined for Ap4A and related dinucleoside polyphosphates, and various gene family members exist (human and microbial)[2][7][5]. No clinically approved drugs specifically target these enzymes as of 2024.

Other names

Diadenosine polyphosphate hydrolaseDiadenosine tetraphosphate hydrolaseAp4A hydrolaseApnA hydrolaseNp_n_N hydrolaseNudix hydrolaseEC 3.6.1.17 (asymmetrical Ap4A hydrolase)EC 3.6.1.41 (symmetrical Ap4A hydrolase)ApaH (in bacterial systems)

Inhibitors act by blocking catalytic hydrolysis of dinucleoside polyphosphates, potentially altering cellular signaling and nucleotide metabolism[1][5].