Metabolism of N-(purin-6-ylcarbamoyl)-L-threonine riboside in rat and man

N-(purin-6-ylcarbamoyl- L -threonine riboside-8-14C (Ado-CO-thr-8-14C) and N-(purin-6-ylcarbamoyl- l -[U-14C]threonine riboside (Ado-CO-thr-14C) were synthesized by using adenosine-8-14C and threonine [U-14C], respectively, as labeled starting materials. The Ado-CO-thr-8-14C and Ado-CO-thr-14C were given intravenously and orally to rat and to man. Of the 2·4 × 106 dis/min administered intravenously to rats, 73 per cent was excreted in urine. More than 79 per cent of this excreted activity was in unchanged Ado-CO-thr, 2·2 per cent in the free base, N-(purin-d-ylcarbamoyl)- l -threonine (Ade-CO-thr), and less than 2 per cent in adenosine. Radioactivity in adenine, inosine, hypoxanthine and uric acid was less than 0·1 per cent. When the labeled Ado-CO-thr was administered orally, less than 5 per cent of the radioactivity was excreted in urine. Similar results were obtained in man. These data revealed that Ado-CO-thr is quite a stable modified nucleoside in vivo. Intravenously administered, Ado-CO-thr was not incorporated into rat t-RNA. In vitro, it did not serve as a substrate for adenosine deaminase, xanthine oxidase and adenosine kinase. Incubation of Ado-CO-thr with urease, acylase, protease, peptidases and similar other enzymes did not lead to any structural change in the molecule. It is suggested that naturally occurring urinary Ado-CO-thr originates from t-RNA and is excreted quantitatively in urine.