The Formation of Adenosine in Rabbit Liver and Its Possible Role as a Direct Precursor of Erythrocyte Adenine Nucleotides

Abstract

Abstract The possible role of the liver, as a source of purine and purine derivatives, for the synthesis of purine nucleotides in other tissues was investigated by studying the formation and release of these compounds under conditions of in situ perfusion. Rabbit liver perfused in situ with labeled [3H]adenine and then with an oxygenated solution containing unlabeled adenosine yielded labeled adenosine both in the liver and in the hepatic venous effluent. As the period of perfusion proceeded, there was an increase in the percentage of radioactivity associated with the adenosine in the hepatic effluent and a decrease in the percentage of radioactivity associated with free adenine. Similar results were obtained in a comparable experiment with [3H]hypoxanthine labeling, but the percentage of radioactivity associated with adenosine was not as great and there was no detectable formation of labeled adenine. The specific activities of the acid-soluble purine derivatives of the liver suggest initial incorporation of the labeled purine into nucleotides followed by conversion to nucleosides. The perfusion of rabbit liver in situ with [3H]hypoxanthine and then with a suspension of oxygenated washed human erythrocytes, in an isotonic solution containing plasma, resulted in the transfer of radioactivity from the liver to the adenine nucleotides within the human erythrocytes of the perfusate. A similar pattern of transfer was observed with slices prepared from rabbit liver, previously labeled in situ with [3H]hypoxanthine, and then incubated in vitro with human and rabbit erythrocyte suspensions. Since the mature human erythrocyte does not possess the capacity to convert inosine 5'-monophosphate to adenosine 5'-monophosphate, the source of the labeled purine moiety in the human cell is limited to adenine or adenosine. This study suggests that adenosine, formed within and released from the liver, may play a role in the maintenance and renewal of adenine nucleotides within human and rabbit erythrocytes.