Stability of AMP: Pyrophosphate phosphoribosyltransferase, an autosomally determined enzyme in an X-linked disease identification of a destabilizer

Charles S. Rubin, M. Earl Balis

Research output: Contribution to journalArticle

4 Scopus citations


The stability of AMP: pyrophosphate phosphoribosyltransferases (AMP pyrophosphorylase) from erythrocytes of normal subjects and patients with Lesch-Nyhan disease has been studied. Storage of intact cells, but not lysates, led to increased heat stability of the normal but not the Lesch-Nyhan enzyme. Passage of lysates of stored normal erythrocytes through Sephadex gave a further increase in the heat stability of AMP pyrophosphorylase. Boiled extracts of stored erythrocytes contained a potent destabilizer of the enzyme which was identified as hypoxanthine. A heat stable form of AMP pyrophosphorylase was generated by pre-incubation with 5-phosphoribosyl i-pyrophosphate, a substrate. These observations suggest that the level of AMP pyrophosphorylase in the erythrocyte may be controlled by the relative concentrations of stabilizer and destabilizer. A variety of purine derivatives were destabilizers of the enzyme. Compounds with 6-amino substituents were active with the normal and Lesch-Nyhan enzyme but 6-hydroxypurines affected only normal AMP pyrophosphorylase. AMP pyrophosphorylases were purified 200-fold from normal and Lesch-Nyhan erythrocytes. The purified enzymes retained some of the differences in stability seen with crude lysates, but the destabilizing effect of purines was lost.

Original languageEnglish (US)
Pages (from-to)163-174
Number of pages12
JournalBBA - General Subjects
Issue number1
Publication statusPublished - Aug 18 1972


ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this