| Autor: |
Holstege, Axel, Schulz-Holstege, Christa, Henninger, Hanspeter, Reiffen, Karl A., Schneider, Friedhelm, Keppler, Dietrich O. R. |
| Předmět: |
|
| Zdroj: |
European Journal of Biochemistry; 1/4/82, Vol. 121 Issue 2, p469-474, 6p |
| Abstrakt: |
The interference of nucleotide metabolism induced by D-arabino-hexos-2-ulose (glucosone), 2-deoxy-2-fluoro- D-glucose (fluoroglucose) and, for comparison, 2-amino-2-deoxy-D-glucose (glucosamine) was studied in suspension cultures of TA3 mammary tumor cells. High-performance liquid chromatography, [14C]uridine labeling and enzymatic analyses revealed that glucosone is metabolized to the UDP derivative leading to a diversion of [14Cluridylate from UTP into UDP-glucosone. The accumulation of UDP-glucosone, that was measured in TA3 as well as AS-30D hepatoma cells, was associated with a depletion of UTP pools to less than 15% of control and a reduction of CTP contents to one third. UTP and CTP deficiency could be rapidly reversed by addition of uridine to the cell suspension. Fluoroglucose acted both as a uridylate-trapping and as a guanylate-trapping hexose analog lowering the cellular contents of UTP and GTP to 5% and 27% of control, respectively. The lowering of GTP was accompanied by an increase in total acid-soluble guanine nucleotides and a diversion of 84% of the [14C]guanylate into GDP-fluoroglucose. As compared to fluoroglucose and glucosone, glucosamine was less effective in TA3 cells in decreasing the content of UTP. The uridylate-trapping effect of glucosamine was in part compensated by the most active expansion of the acid-soluble uridylate pool; this reflects an enhanced rate of de novo pyrimidine synthesis that could be suppressed by the inhibitor 6-azauridine. As a side effect probably resulting from phosphate trapping, glucosone, fluoroglucose, and glucosamine depressed the levels of ATP and of total adenine 5'-nucleotides to a similar though moderate extent. The depletion of UTP, induced by these C-2-modified D-glucose analogs, and additionally of GTP in the case of fluoroglucose, represent a metabolic lesion that may explain their growth inhibitory and cytotoxic effects. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
