Transfer of Resistance to Selective Conditions from Fibroblasts with Mutant Feedback-Resistant Phosphoribosylpyrophosphate Synthetase to Normal Cells

A Form of Metabolic Cooperation
  • E. Zoref
  • A. de Vries
  • O. Sperling
Part of the Advances in Experimental Medicine and Biology book series


A mutant phosphoribosylpyrophosphate (PRPP) synthetase, recently found in our laboratory to be the primary abnormality underlying the excessive purine production in a family affected with primary metabolic gout (1,2), was used as a marker for the study of metabolic cooperation between cultured human fibroblasts (3). In physiological cellular milieu, the mutation is manifest in superactivity of the enzyme which is due to decreased sensitivity to feedback inhibition by several physiological intracellular inhibitors such as adenosine-5′-diphosphate, guanosine-5′-diphosphate and 2,3-diphosphoglyceric acid. The superactivity of the enzyme was shown to cause increased availability of its reaction product PRPP, a key substrate for both the de novo and salvage pathways of purine nucleotide synthesis. Accordingly, the mutant cell exhibits excessive de novo synthesis of purines as well as an improved capacity to synthesize purine nucleotides by the salvage pathway. Both properties render the mutant cell a suitable marker for the study of metabolic cooperation, the increased salvage capacity allowing selection between normal and mutant cells, and the excessive de novo purine synthesis allowing determination of the proportion of mutant cells in culture containing a mixture of mutant and normal cells.


Mutant Cell Thymidine Kinase High Cell Density Salvage Pathway Selective Condition 
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Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • E. Zoref
    • 1
    • 2
  • A. de Vries
    • 1
    • 2
  • O. Sperling
    • 1
    • 2
  1. 1.Department of Chemical PathologyTel-Aviv University Medical SchoolTel-HashomerIsrael
  2. 2.Rogoff-Wellcome Medical Research InstituteBeilinson Medical CenterPetah TikvaIsrael

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