1973
DOI: 10.1093/jnci/51.3.1013
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Glutamate-Mediated Respiration in Tumors2

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Cited by 17 publications
(7 citation statements)
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“…Salvage pathway of adenine nucleotide biosynthesis (from Kornberg, 1974) tion could not be overcome by supplementation of any of these amino acids (Zetterberg and Engstrom, 1981). Glutamine is also an important source of respiratory fuel for normal as well as for malignant cells in culture (Kovacevic and Morris, 1972;Regan et al, 1973;Reitzer et al, 1979;Meister, 1979;Wice et al, 1981;McKeehan, 1982). If glutamine exerted a key regulatory role via the cellular energy metabolism, one might have expected that the concomitant withdrawal of glutamine and the other main energy source-glucose-from the medium would result in a further inhibition of DNA synthesis.…”
Section: Discussionmentioning
confidence: 99%
“…Salvage pathway of adenine nucleotide biosynthesis (from Kornberg, 1974) tion could not be overcome by supplementation of any of these amino acids (Zetterberg and Engstrom, 1981). Glutamine is also an important source of respiratory fuel for normal as well as for malignant cells in culture (Kovacevic and Morris, 1972;Regan et al, 1973;Reitzer et al, 1979;Meister, 1979;Wice et al, 1981;McKeehan, 1982). If glutamine exerted a key regulatory role via the cellular energy metabolism, one might have expected that the concomitant withdrawal of glutamine and the other main energy source-glucose-from the medium would result in a further inhibition of DNA synthesis.…”
Section: Discussionmentioning
confidence: 99%
“…A comparison of the rate of oxygen consumption, glutaminase activity, and carbon dioxide production in the presence of glutamine, glucose, glutamate, and pyruvate suggested that glutamine was potentially the most important substrate for oxidative metabolism in rapidly proliferating, malignant hepatoma cells (Kovacevic, 1971;Kovacevic and Morris, 1972). Fluoropyruvate and vinblastine inhibited oxygen uptake in sarcoma 180 and three Morris hepatoma cell lines (Regan et at., 1973). The inhibition could be reduced by increasing the level of glutamate in the culture medium.…”
Section: Hepatomasmentioning
confidence: 99%
“…1. From this perspective, 620 mitochondrial function may be quantitatively different in cancer cells vs. normal cells dependent upon substrate preference [4], for example shifting more to the biosynthetic mode and glutamate utilization [5] with aerobic glycolysis providing ATP (the Warburg effect [6]). One approach to mimic this metabolic difference in normal cells is to challenge keto acid pool homeostasis by limiting the nutrient input as has been done for cancer cells.…”
Section: Introductionmentioning
confidence: 99%
“…The resulting alpha ketoglutarate (αKG) formed by deamination of glutamate can be converted to malate and, if malate exits the mitochondria and is converted to pyruvate in the cytosol, this keto acid can reenter the cycle contributing to pool homeostasis [7]. However, if pyruvate's entrance into the cycle is blocked as may occur in tumor cells [5,8], then lowered cycle alpha ketoglutarate effectively "pulls" glutamate via GDH supplying net keto acid just as occurs in glucose withdrawal. However, in contrast to glucose withdrawal, pyruvate formed from malate in the cytosol would be unable to reenter the mitochondria, and, as a default pathway, glycolysis and lactate accumulation could occur (the Warburg effect, Fig.…”
Section: Introductionmentioning
confidence: 99%