3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1) (BPNT1)

3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1), commonly known as pAp-phosphatase, is a magnesium-dependent enzyme that plays a vital role in cellular metabolism by degrading 3'-phosphoadenosine 5'-phosphate (pAp) [1, 4, 18]. This nucleotide is a byproduct of sulfation reactions, and its accumulation is toxic as it inhibits various sulfotransferases and RNA processing enzymes [4, 22, 23]. BPNT1 converts pAp into adenosine 5'-monophosphate (AMP) and inorganic phosphate, thereby maintaining metabolic homeostasis [4, 17]. The enzyme is a member of the lithium-inhibited phosphatase family and is potently inhibited by lithium at therapeutic concentrations through an uncompetitive mechanism [2, 5, 10, 17]. This inhibition is believed to contribute to both the therapeutic efficacy and the side effects, such as nephrotoxicity, of lithium treatment for bipolar disorder [5, 14, 17]. Beyond its role in sulfur and nucleotide metabolism, BPNT1 is involved in inositol recycling and has been recently identified as an oncogenic driver in triple-negative breast cancer, where it promotes tumor progression and resistance to chemotherapy [6, 11]. Its diverse roles in psychiatric, metabolic, and oncogenic processes make it a target of significant therapeutic interest [6, 17].

Other names

pAp-phosphatasePAP phosphataseBisphosphate 3'-nucleotidase 13'-phosphoadenosine 5'-phosphate phosphataseInositol-polyphosphate 1-phosphataseBPntase 1HsPIPHEL20PIP

Lithium acts as an uncompetitive inhibitor of the enzyme, binding to the enzyme-substrate complex and preventing the release of products, which leads to the accumulation of adenosine 3',5'-bisphosphate (pAp).