Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-Asparagine synthesis in Saccharomyces cerevisiae is performed by a glutamine-dependent asparagine synthetase of the type found in higher organisms. Auxotrophy for asparagine has been obtained in two classes of mutants. In class I, asparagine synthetase activity is cancelled. These mutants combine two mutations, asnA- and asnB-. Neither asnA- nor asnB- mutation alone leads to total auxotrophy. Partial auxotrophy as well as a strong decrease in enzyme activity result from asnA- mutation. No change is detectable in cells with the asnB- mutationalone. This, and Jones' report [J. Bacteriol. 134, 200-207 (1978)] of auxotrophy resulting from the combination of two mutations, are strong supports for asparagine synthesis being an unusual biosynthetic operation. In class II, auxotrophy results from a single mutation which leads to a modification of the efficiency of the asparaginyl-tRNA synthetase (asnRS- mutation). This auxotrophy is cancelled if asparaginase I activity (the only one present in sigma 1278b wild type) is cancelled by casnI- mutation. This latter mutation allows an increase in the asparagine pool which is able to compensate for the asparaginyl-tRNA synthetase partial defect of the asnRS- mutant.
 ...
PMID:Synthesis and activation of asparagine in asparagine auxotrophs of Saccharomyces cerevisiae. 3 16

1. The mouse Gardner lymphoma 6C3HED was grown in ascites fluid in a form sensitive to the action of L-asparaginase (line 1), in another form which was resistant to L-asparaginase (line 2) and in a third form with partial sensitivity to L-asparaginase (line 3). 2. The L-asparaginyl-tRNA synthetase activities of extracts of the tumour cells, cultured both in the mouse and in vitro, were determined. Two of the lines, 1 and 3, in early passage numbers, showed a derepression mechanism involving L-asparagine. Mutation occurred with these lines resulting in the L-asparaginyl-tRNA synthetase activity of all the tumour cell lines being the same. 3. Cells of line 1 had low L-asparagine synthetase activity, which was unchanged by altering the supply of L-asparagine in vitro. Cells of lines 2 and 3 exhibited L-asparagine synthetase activities, which changed with the supply of L-asparagine. 4. It is not certain that L-asparagine synthetase activity of L-asparaginase-sensitive cells is controlled by L-asparaginyl-tRNA acting as a corepressor.
 ...
PMID:L-asparaginyl-tRNA synthetase and L-asparagine synthetase activities of L-asparaginase-sensitive and -resistant forms of the mouse Gardner lymphoma 6C3HED. 3 36

The cell-killing activity of asparaginase on three classes of Chinese hamster ovary cell mutants was examined: a mutant which overproduces asparagine synthetase (AH5); mutants defective in asparagine synthetase (N3 and N4); and mutants conditionally defective in asparagyl-transfer RNA synthetase (Asn 3, Asn 7, and Asn 9). The overproducer was more resistant to the cell-killing activity of asparaginase than wild-type Chinese hamster ovary cells, while mutants defective in asparagine synthetase were more sensitive. Surprisingly, the asparagyl-transfer RNA synthetase mutants were even more sensitive to asparaginase than the asparagine synthetase mutants. In a preliminary survey of four human lymphoid cell lines (RPMI 8402, RPMI 8392, B46M, and Molt-4F) which showed dramatically different asparaginase sensitivity, however, sensitivity to the cell-killing activity of asparaginase was correlated with reduced levels of asparagine synthetase and not with reduced levels of asparagyl-transfer RNA synthetase.
 ...
PMID:Role of asparaginase synthetase and asparagyl-transfer RNA synthetase in the cell-killing activity of asparaginase in Chinese hamster ovary cell mutants. 611 89