Chapter title |
Mammalian mutants genetically altered in CTP synthetase activity.
|
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Chapter number | 42 |
Book title |
Purine and Pyrimidine Metabolism in Man V
|
Published in |
Advances in experimental medicine and biology, January 1986
|
DOI | 10.1007/978-1-4684-1248-2_42 |
Pubmed ID | |
Book ISBNs |
978-1-4684-1250-5, 978-1-4684-1248-2
|
Authors |
Aronow, B, Ullman, B, Aronow, Bruce, Ullman, Buddy |
Abstract |
From wildtype mouse lymphoma cells, a clone (FURT-1A), was isolated by virtue of its resistance to 1 microM 5-fluorouracil. In comparative growth rate experiments, FURT-1A cells were also less sensitive than parental cells to the growth inhibitory effects of thymidine, deoxyguanosine, 5-fluorouridine, and arabinosylcytosine. The altered growth sensitivity of FURT-1A cells to cytotoxic nucleosides was directly related to their decreased ability to accumulate the corresponding triphosphate from exogenous nucleoside. FURT-1A cells contained elevated cytidylate nucleotide pools which prevented normal growth sensitivity and interfered with the salvage of nucleosides. Metabolic flux experiments with [3H]-uridine in situ indicated that FURT-1A cells had a 2-fold enhanced rate of conversion of UTP to CTP. Kinetic analyses indicated that the CTP synthetase activity in extracts of FURT-1A cells was refractory to inhibition by CTP. The genetic loss of normal allosteric inhibition of the CTP synthetase activity in FURT-1A cells could account for the unusual phenotypic properties of these cells. |
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