non-nucleoside

Inosine Triphosphate Pyrophosphatase (ITPase) is a cytoplasmic enzyme that belongs to the HAM1 NTPase family. ITPase hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP) and deoxyinosine triphosphate (dITP) to the monophosphate nucleotide (IMP) and diphosphate. The ITPase enzyme acts as a homodimer and does not distinguish between the deoxy- and ribose forms. ITPase probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. Defects in ITPase is thought to be inherited and is characterized by an over-accumulation of ITP in erythocytes, leukocytes and fibroblasts.

Phosphorylates deoxyguanosine and deoxyadenosine in the mitochondrial matrix, with the highest efficiency for deoxyguanosine. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on DGUOK and TK2. Phosphorylates certain nucleoside analogs. Widely used as target of antiviral and chemotherapeutic agents.

DCTPP1 hydrolyzes deoxynucleoside triphosphates (dNTPs) to the corresponding nucleoside monophosphates. It has a strong preference for modified dCTP. DCTPP1’s activity is highest with 5-iodo-dCTP, followed by 5-bromo-dCTP, unmodified dCTP, 5-methyl-dCTP and 5-chloro-dCTP. DCTPP1 also hydrolyzes 2-chloro-dATP and 2-hydroxy-dATP with lower efficiency, and has even lower activity with unmodified dATP, dTTP and dUTP (in vitro). DCTPP1 does not hydrolyze ATP, UTP, ITP, GTP, dADP, dCDP or dGTP. It may protect DNA or RNA against the incorporation of non-canonical nucleotide triphosphates. DCTPP1 may also protect cells against inappropriate methylation of CpG islands by DNA methyltransferases.