Reactome | ITPA dimer dephosphorylates RBV-TP to RBV-MP

ITPA dimer dephosphorylates RBV-TP to RBV-MP

Stable Identifier

R-HSA-9755030

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

ITPA dimer hydrolyzes RBV-TP

ReviewStatus

5/5

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ITPA dimer dephosphorylates RBV-TP to RBV-MP

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Ribavirin triphosphate (RBV-TP) was dephosphorylated in vitro by recombinant ITP triphosphatase (ITPAse, ITPA) to a similar extent as its naturally occurring substrate ITP. Reduced ITPase activity in one third of humans causes increased intracellular levels of RBV-TP, leading to increased treatment efficacy (Nystrom et al, 2018; Tanaka et al, 2018). Polymorphisms in the gene encoding ITPase (ITPA) have been associated with protection against ribavirin-induced anemia (Fellay et al, 2010).

Literature References

PubMed ID	Title	Journal	Year
29580856	Induction of inosine triphosphatase activity during ribavirin treatment for chronic hepatitis C Tanaka, Y, Yokomori, H, Otori, K	Clin Chim Acta	2018
30045981	Inosine Triphosphate Pyrophosphatase Dephosphorylates Ribavirin Triphosphate and Reduced Enzymatic Activity Potentiates Mutagenesis in Hepatitis C Virus Nyström, K, Wanrooij, PH, Waldenström, J, Adamek, L, Brunet, S, Said, J, Nilsson, S, Wind-Rotolo, M, Hellstrand, K, Norder, H, Tang, KW, Lagging, M	J Virol	2018
20173735	ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C Fellay, J, Thompson, AJ, Ge, D, Gumbs, CE, Urban, TJ, Shianna, KV, Little, LD, Qiu, P, Bertelsen, AH, Watson, M, Warner, A, Muir, AJ, Brass, C, Albrecht, J, Sulkowski, M, McHutchison, JG, Goldstein, DB	Nature	2010