Studies on 5-aminouridine
1966; Elsevier BV; Volume: 119; Issue: 2 Linguagem: Inglês
10.1016/0005-2787(66)90180-8
ISSN1879-3002
AutoresDavid A. Smith, Pradip Roy‐Burman, Donald W. Visser,
Tópico(s)Folate and B Vitamins Research
ResumoAbstract Inhibitory effects of 5-aminouridine and 5-aminouridylic acid were studied in Ehrlich ascites cells and cell-free preparations. The metabolism of synthetically prepared [2- 14 C]5-aminouridine was compared with that of [2- 14 C]uridine. The radioactive nucleoside analogue was metabolized to 5-amino-UMP in Ehrlich ascites cells and evidence for the presence of 5-amino-UDP, 5-amino-UTP and 5-amino-UDP-sugars in the acid-soluble fraction was obtained. Incorporation of analogue into RNA was proven by isolation of radioactive 5-aminouridine 2′(3′)-monophosphate from an alkaline hydrolysate of RNA isolated from the cells. The presence of 5-aminouridine 5′-phosphate inhibited formation of uridine nucleotides from [2- 14 C]orotic acid and caused accumulation of orotidylic acid in cell-free preparations from Ehrlich ascites cells. The data demonstrate that 5-aminouridine 5′-monophosphate is a potent inhibitor of orotidine-5′-phosphate decarboxylase (EC 4.1.1.23). Ehrlich ascites cells were incubated in the presence of equal amounts of either [2- 14 C]uridine or [2- 14 C]5-aminouridine to determine quantitative differences in the metabolism of the two compounds. Differences in the amounts of [2- 14 C]uridine and [2- 14 C]5-aminouridine in the respective acid-soluble nucleotides were no greater than 2-fold. The amount of [2- 14 C]uridine incorporated into nucleic acids, however, was 6.7 times greater than that of [2- 14 C]5-aminouridine.
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