Metabolic cooperation between human fibroblasts with normal and with mutant superactive phosphoribosylpyrophosphate synthetase

Nature (Impact Factor: 41.46). 05/1976; 260(5554):787-8. DOI: 10.1038/260786a0
Source: PubMed


METABOLIC cooperation is a form of intercellular communication by which cells in contact exchange molecules, a process providing multicellular organisms with an important mechanism for control of metabolic activity1. Subak-Sharpe et al.2 observed contact-dependent transfer of purine nucleotides from normal cells to cells mutationally incapable of producing inosinic acid due to deficiency in hypoxanthine-guanine phosphoribosyl-transferase3. Metabolic cooperation of this type was later also demonstrated with other enzymic markers, such as adenine phosphoribosyltransferase and thymidine kinase4,5. Such transfers are characterised, by the normal cell being the donor and the mutant cell being the recipient, the former transferring to the latter a mutationally lacking metabolite. We report here on a new form of contact-dependent metabolic cooperation, unique in that the transfer of a metabolite occurs from a mutant donor cell to a normal recipient cell.

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    ABSTRACT: Skin fibroblast cultures were utilized to study the mode of inheritance of a mutant feedback-resistant phosphoribosylpyrophosphate synthetase in a gouty family with purine overproduction. Selective conditions were applied to allow the survival in culture of mutant cells only. Whereas in the male gouty propositus the cell culture was homogeneous for the mutant enzyme, in the cell culture from his nongouty mother two cell populations were demonstrated, one normal and the other mutant. The mosaicism in the mother is compatible with X-linkage of the enzyme. From this finding, together with the clinical and biochemical data available, it is concluded that in this family the enzyme mutation is transmitted in a X-linked recessive pattern.Copyright © 1977 S. Karger AG, Basel
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