Metabolic fate of hypoxanthine and inosine in cultured cardiomyocytes

Esther Zoref-Shani, Yael Bromberg, Chaim Shirin, Yechezkel Sidi, Oded Sperling*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The metabolic fate of labeled hypoxanthine and inosine, degradation products of adenine nucleotides, was studied in cultured beating cardiomyocytes, in order to assess the physiological significance of their contribution to salvage nucleotide synthesis in the heart. Inosine and hypoxanthine were found to be incorporated into nucleotides by a similar rate, but in the presence of 8-aminoguanosine, a potent inhibitor of purine nucleoside phosphorylase (EC 2.4.2.1), the rate of inosine incorporation into nucleotides was markedly reduced (by 75%), indicating that inosine incorporation to IMP (inosinic acid) occurs following its degradation to hypoxanthine. The proportion of hypoxanthine converted to IMP by hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) is markedly greater than that degraded to xanthine and uric acid by xanthine oxidase (EC 1.3.2.3). However, close to 50% of the IMP formed was degraded to inosine by IMP 5′-nucleotidase (EC 3.1.3.5). The results demonstrate the activity of the following futile cycle in the cardiomyocytes: hypoxanthine → IMP → inosine → hypoxanthine. The rational for the activity of this energy consuming cycle is yet unclear.

Original languageEnglish
Pages (from-to)183-189
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume24
Issue number2
DOIs
StatePublished - Feb 1992

Keywords

  • 8-aminoguanosine
  • Cardiomyocytes
  • Hypoxanthine
  • IMP-5′-nucleotidase
  • Inosine
  • Purine nucleoside phosphorylase
  • Salvage nucleotide synthesis

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