INTERRELATIONS BETWEEN SUBSTRATE CYCLES AND DENOVO SYNTHESIS OF PYRIMIDINE DEOXYRIBONUCLEOSIDE TRIPHOSPHATES IN 3T6 CELLS
INTERRELATIONS BETWEEN SUBSTRATE CYCLES AND DENOVO SYNTHESIS OF PYRIMIDINE DEOXYRIBONUCLEOSIDE TRIPHOSPHATES IN 3T6 CELLS
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DOI：
10.1073/pnas.83.4.986
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发表时间：
1986-02-01
影响因子：
11.1
通讯作者：
REICHARD, P
中科院分区：
文献类型：
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作者：
BIANCHI, V;PONTIS, E;REICHARD, P
在3T6细胞中，嘧啶脱氧核糖核苷三磷酸的降解在其池大小的调节中起主要作用。在正常生长过程中，这些细胞将脱氧核糖核苷（主要是脱氧尿苷）分泌到培养基中。当DNA链延伸被抑制时，dCTP和dTTP的重新合成继续进行，随后是脱氧核糖核苷酸的降解。我们现在证明，抑制羟基脲从头合成可以阻止脱氧核糖核苷酸的降解，并导致脱氧尿苷从培养基中流入。这种影响似乎是由细胞内dUMP池大小的大幅下降引起的。我们提出底物循环，包括激酶对脱氧核糖核苷的磷酸化和核苷酸酶对脱氧核糖核苷5' -磷酸的去磷酸化，通过指导脱氧核糖核苷在细胞膜上的流动，参与嘧啶脱氧核糖核苷三磷酸池大小的调节。虽然激酶主要受变构效应的调节，但核苷酸酶的活性似乎受底物浓度的调节。
Degradation of pyrimidine deoxyribonucleoside triphosphates plays a major role in the regulation of their pool sizes in 3T6 cells. During normal growth, these cells excrete deoxyribonucleosides (mostly deoxyuridine) into the medium. When DNA strand elongation is inhibited, de novo synthesis of dCTP and dTTP continues, followed by degradation of the deoxyribonucleotides. We now demonstrate that inhibition of de novo synthesis with hydroxyurea stops degradation of deoxyribonucleotides and leads to an influx of deoxyuridine from the medium. This effect appears to be caused by a large drop in the size of the intracellular dUMP pool. We propose that substrate cycles, involving phosphorylation of deoxyribonucleosides by kinases and dephosphorylation of deoxyribonucleoside 5''-phosphates by a nucleotidase, participate in the regulation of the size of pyrimidine deoxyribonucleoside triphosphate pools by directing the flow of deoxyribonucleosides across the cell membrane. While kinases are regulated mainly by allosteric effects, the activity of the nucleotidase apepars to be regulated by substrate concentration.