Mutant cell lines resistant to azetidine‐2‐carboxylic acid: Alterations in the synthesis of proline from glutamic acid

Ronna F. Lodato, Robert J. Smith, David L. Valle, Kathleen Crane

Research output: Contribution to journalArticle

Abstract

Two mutant Chinese hamster lung fibroblast lines have been isolated that are resistant to the the toxic proline analog L‐azetidine‐2‐carboxylic acid. The line designated AZCA‐1 has 30‐fold elevated activity of pyrroline‐5‐carboxylate synthase and a large increase in the rate of proline production and release compared to controls. Pyrroline‐5‐carboxylate synthase activity is not elevated in the resistant line designated AZCA‐4, but the enzyme is less sensitive to inhibition by ornithine and proline than control enzyme. Intracellular proline is elevated in AZCA‐4 cells, with no change in the rate of release of proline synthesized from glutamate. Resistance to azetidine carboxylic acid in both mutant lines is attributed to the expanded intracellular proline pool that results from alterations in pyrroline‐5‐carboxylate synthase. These results indicate that intracellular proline levels are determined at least in part by the regulated activity of pyrroline‐5‐carboxylate synthase.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalJournal of Cellular Physiology
Volume119
Issue number1
DOIs
StatePublished - Apr 1984

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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