Inosine Triphosphate Pyrophosphatase (ITPase): Functions, Mutations, Polymorphisms and Its Impact on Cancer Therapies

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Inosine triphosphate pyrophosphatase (ITPase), encoded by the ITPA gene, hydrolyzes (deoxy)nucleoside triphosphates ((d)NTPs).
• ITPase prevents incorporation of noncanonical purines into DNA/RNA and processes thiopurine drug metabolites.
• ITP/XTP and dITP/dXTP are biological reaction products, and ITPA gene variations are linked to diseases.

Purpose of the Study:

• To provide an updated review of the inosine triphosphate pyrophosphatase (ITPase) enzyme.
• To cover ITPase discovery, analysis, cellular localization, and disease implications.
• To explore the therapeutic potential of ITPase.

Main Methods:

• Literature review of ITPase research.
• Analysis of ITPase function in nucleotide metabolism.
• Examination of ITPA gene polymorphisms and associated human diseases.

Main Results:

• ITPase plays a critical role in preventing the incorporation of potentially harmful nucleotides.
• ITPA gene deficiency or polymorphisms are implicated in infantile epileptic encephalopathy, tuberculosis, and cancer therapy response.
• Thiopurine drug metabolites are identified as substrates for ITPase.

Conclusions:

• ITPase is a crucial enzyme in cellular metabolism with significant implications for human health.
• Understanding ITPase function and its genetic variations is vital for disease diagnosis and treatment, particularly in cancer therapy.
• ITPase represents a potential therapeutic target for various human diseases.