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

3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1) is a highly conserved, magnesium-dependent enzyme that hydrolyzes 3'-phosphoadenosine 5'-phosphate (PAP), a byproduct of sulfur transfer reactions. BPNT1 plays a crucial homeostatic role by preventing toxic accumulation of PAP, a metabolite that—if not cleared—can disrupt multiple metabolic and gene-regulatory pathways. Alongside associated sulfur assimilation, BPNT1 indirectly impacts inositol signaling, nucleotide turnover, and cellular metabolic homeostasis. It is sensitive to inhibition by lithium, a drug widely used in psychiatric treatment, and lithium's inhibition of BPNT1 is linked to clinical side effects such as nephrotoxicity and neurological disturbances. In murine models, BPNT1 deficiency leads to iron-deficiency anemia and pronounced liver dysfunction, marked by impaired protein synthesis, nucleolar alterations, and tissue lipid accumulation. BPNT1 is thus an essential intracellular enzyme with notable roles in health and disease, connecting metabolism, RNA processing, and pharmacological toxicity[1][3][4].

Other names

BPNT1Bisphosphate 3'-nucleotidase 1BPntase 1PAP phosphatase3'-phosphoadenosine 5'-phosphate phosphataseHsPIPInositol-polyphosphate 1-phosphataseEpididymis luminal protein 20Testicular tissue protein Li 29

Inhibition of BPNT1 by lithium leads to accumulation of PAP and altered cellular metabolism, which can produce nephrotoxicity and neurobehavioral side effects[1][4].