Asparagine and glycine metabolism in rat liver mitochondria and in mouse L5178Y lymphoma cells resistant or sensitive to the anticancer drug L-asparaginase
Rat liver mitochondrial asparagine was found to be degraded via an aminotransferase and omega-amidase. Evidence includes oxaloacetate production from asparagine only when glyoxylate was added and production of radiolabeled ..cap alpha..-ketosuccinamate via metabolism of (U-/sup 14/C)asparagine. In the cytosol, asparagine is degraded primarily via asparaginase and subsequent transamination. A new HPLC technique for separation of citric acid cycle intermediates was developed using: ion pairing with 20 mM each to tetrabutylammonium hydroxide and Na/sub 2/SO/sub 4/; pH 7.0; isocratic elution; and detection at 210 nm. Amino acid content of mouse lymphoma cells either sensitive (L5178Y) or resistant (L5178Y/L-ASE) to the anticancer drug L-asparaginase was studied. The concentration of asparagine was 1.5 times higher and the concentrations of the essential amino acids histidine, methionine, valine and phenylalanine were two times higher in asparaginase-resistant than sensitive cells. In vivo but not in vitro studies indicated that glucine decreases in sensitive but not resistant cells upon asparaginase treatment. Asparagine and glycine metabolism was further studied using /sup 14/C radiolabel conversion of asparagine, glyoxylate, glycine and serine. Glycine metabolism is especially important in lymphomas and leukemias because these cells contain higher concentrations of glycine that other cancer and normal cells. Therefore, glycine levels were studied and were found to decrease in sensitive but not resistant cells upon asparaginase administration.
- Research Organization:
- Nebraska Univ., Lincoln (USA)
- OSTI ID:
- 7065698
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ASPARAGINE
METABOLISM
CARBON 14 COMPOUNDS
GLYCINE
MITOCHONDRIA
BIOCHEMISTRY
ENZYME ACTIVITY
TUMOR CELLS
AMINOTRANSFERASES
CARBON 14
CHROMATOGRAPHY
LIQUID COLUMN CHROMATOGRAPHY
LIVER
LYMPHOMAS
MICE
RATS
AMIDES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBON ISOTOPES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMISTRY
DIGESTIVE SYSTEM
DISEASES
ENZYMES
EVEN-EVEN NUCLEI
GLANDS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
NEOPLASMS
NITROGEN TRANSFERASES
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
RADIOISOTOPES
RODENTS
SEPARATION PROCESSES
TRANSFERASES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques