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- W2000338894 abstract "Adenine and guanine nucleosides and deoxynucleosides inhibit methionine synthesis in cultured human T and B lymphoblasts; the deoxynucleosides are more potent inhibitors than the corresponding nucleosides and T lymphoblasts are more sensitive than B lymphoblasts (J. Clin. Invest. 74:1262-1268, 1984). Since homo-cysteine largely reverses the methionine synthesis inhibition, it appears that the mechanism is through S-adenosylhomocysteine hydrolase inhibition with a consequent decrease in intracellular homocysteine synthesis. Because the 5,10-methylenetetrahydrofolate reductase reaction is functionally irreversible in vivo, reduced intracellular homocysteine production should lead to trapping of folates as 5-methyltetrahydrofolate and thus to decreased purine synthesis. This hypothesis was tested in cultured T and B lymphoblasts. To eliminate inhibition of the first reaction of the de novo pathway, cells were treated with azaserine and aminoimidazolecarboxamide; thus, when incubated with [14C]formate only the last step of the pathway is measured. In the T lymphoblasts dAdo and dGuo inhibited purine synthesis significantly at concentrations less than 1 μM whereas it required greater than 3 μM of these deoxynucleosides to inhibit purine synthesis in the B lymphoblasts; at these low concentrations of dAdo and dGuo homocysteine fully reversed the decreased purine synthesis." @default.
- W2000338894 created "2016-06-24" @default.
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- W2000338894 date "1985-07-01" @default.
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- W2000338894 title "DECREASED PURINE AND METHIONINE SYNTHESIS IN PURINE NUCLEOSIDE TREATED T AND B LYHPHOBLASTS: REVERSAL BY HOMOCYSTEINE: 21" @default.
- W2000338894 doi "https://doi.org/10.1203/00006450-198507000-00041" @default.
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