Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Drug
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Target Concepts:
Gene/Protein
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Query: EC:3.5.1.1 (
asparaginase
)
2,695
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Previous work suggested a relationship between glycine metabolism and the effect of
L-asparaginase
upon tumor cells. Therefore, L5178Y (sensitive) or L5178Y/L-
ASE
(resistant) ascites lymphoma cells were incubated with 14C-labeled glyoxylate, glycine, serine, or asparagine, and the metabolism to other amino acids was measured by high performance liquid chromatography. Metabolic differences between the two cells lines were found. Under control conditions, the interconversion rate of glycine and serine via serine hydroxymethyltransferase (SHMT) was higher in sensitive than in resistant cells. The transformation rate of glyoxylate to serine was also higher in sensitive cells. These results may indicate a difference in the activity of SHMT. An alternate explanation would be that transport or diffusion of serine and glycine into sensitive cells is greater than into resistant cells. Several crucial metabolic differences were observed between the two cell types when
L-asparaginase
was added. A key difference is the decrease of glycine synthesis from glyoxylate observed in the sensitive cells compared to resistant cells which show no change. This suggests that asparagine is used for transamination of glyoxylate. Also, only sensitive cells appear to compensate for
L-asparaginase
-induced loss of glycine formation from glyoxylate by increasing glycine synthesis from serine. Alterations in sensitive tumor glycine metabolism may be an important function of
L-asparaginase
anticancer activity.
...
PMID:Comparison of glycine metabolism in mouse lymphoma cells either sensitive or resistant to L-asparaginase. 391 41
The amino acid contents of tumor cells that are either sensitive or resistant to treatment with
L-asparaginase
were measured. These amino acid concentrations were measured as a function of incubation time with
L-asparaginase
or as a function of the
L-asparaginase
dose. The cell types compared were the mouse leukemia lines L5178Y (sensitive to
L-asparaginase
treatment) and L5178Y/L-
ASE
(resistant to
L-asparaginase
treatment). Upon
L-asparaginase
treatment both cell lines lost most of their cellular asparagine but, whereas the resistant cells exhibited the ability to rebound to about 50% of initial values, the sensitive cells did not. While previous work had suggested that asparagine-dependent glycine synthesis was essential for sensitive cells (but not in resistant cells), we found no difference in the glycine content of either of the two cell lines as a function of either time or dose that would support this hypothesis. Major differences between the two cell lines were seen in the content of the essential amino acids before treatment with
L-asparaginase
. After incubation without
L-asparaginase
the contents of the two cell lines became similar. These results are discussed in terms of possible mechanisms of
L-asparaginase
sensitivity and resistance.
...
PMID:Amino acid content of L5178Y and L5178Y/L-ASE cells after L-asparaginase treatment. 408 39
