Title: Production of l-asparagine by tumor cells and the effect of asparagine analogs
Abstract: A rapid assay of the ability of intact cells (10–50 mg) to synthesize l-asparagine and l-aspartic acid, and its application to the evaluation of potential asparagine analogs has been devised. Washed cell preparations were incubated at 37° in Eagle's medium (supplemented with l-glutamine, 2 mM, and l-aspartic acid, 0.05 mM), and the amounts of l-asparagine and l-aspartic acid formed were determined with an enzymatic assay. Murine tumor cells resistant to l-asparaginase produced 1.0 to 1.6 nmoles l-asparagine/mg cells/hr, while sensitive cells produced less than 0.1 nmole/mg cells/hr. The newly synthesized l-aspartic acid was largely localized m the cells; the newly synthesized l-asparagine, however, was distributed both in the cells and in the medium. 5-Diazo-4-oxo-l-norvaline (0.5 mM) and 5-chloro-4-oxo-l-norvaline (0.05 mM) inhibited l-asparagine biosynthesis by P815Y ascites cells 88 and 95 per cent respectively; no significant inhibition of l-aspartic acid biosynthesis was observed with either analog. 5-Bromo-4-oxo-l-norvaline (0.1 mM) caused 78 per cent inhibition of l-asparagine biosynthesis, but also reduced the biosynthesis of l-aspartic acid to 52 per cent.
Publication Year: 1972
Publication Date: 1972-01-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 16
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