Reactome | PNP trimer transforms RBV to T-CONH2

PNP trimer transforms RBV to T-CONH2

Stable Identifier

R-HSA-9755044

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

PNP breaks down ribavirin to T-CONH2

ReviewStatus

5/5

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Significant amounts of ribavirin (RBV) are phosphorolyzed to 1,2,4-triazole-3-carboxamide (T-CONH2), already in the first pass through intestinal cells. The responsible enzyme purine nucleoside phosphorylase (PNP) is expressed in higher amounts in the small intestine than in the liver, which also correlates with higher cytosolic phosphorolysis activity in intestinal cells. The amount of conversion to T-CONH2 in the liver is additionally reduced by phosphorylation of RBV to RBV-MP. T-CONH2 from this reaction is the major metabolite detectable in urine (Paroni et al, 1989; Furihata et al, 2014).

Literature References

PubMed ID	Title	Journal	Year
2737800	Pharmacokinetics of ribavirin and urinary excretion of the major metabolite 1,2,4-triazole-3-carboxamide in normal volunteers Sirtori, CR, Borghi, C, Galli Kienle, M, Paroni, R, Del Puppo, M	Int J Clin Pharmacol Ther Toxicol	1989
24107682	Functional analysis of purine nucleoside phosphorylase as a key enzyme in ribavirin metabolism Furihata, T, Iikura, M, Sugiura, H, Chiba, K, Kamiichi, A, Kishida, S	Drug Metab Pharmacokinet	2014