Metabolism of glutamine in lymphocytes.
Pathways of glutamine metabolism in resting and proliferating rat thymocytes and established human T- and B-lymphoblastoid cell lines were evaluated by in vitro incubations of freshly prepared or cultured cells for one to two hours with [U14C]glutamine. Complete recovery of glutamine carbons utilized in products allowed quantification of the pathways of glutamine metabolism under the experimental conditions. Partial oxidation of glutamine via 2-oxoglutarate in a truncated citric acid cycle to CO2 and oxaloacetate, which then was converted to aspartate, accounted for 76% and 69%, respectively, of the glutamine metabolized beyond the stage of glutamate by resting and proliferating thymocytes. Similar results were obtained with the lymphoblastoid T- and B-cell lines. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for only 25% and 7%, respectively. In proliferating cells a substantial amount of glutamine carbons was also recovered in pyruvate, alanine, and especially lactate. The main route of glutamine and glutamate entrance into the citric acid cycle via 2-oxoglutarate in lymphocytes appears to be transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as a second substrate, glutamine utilization and aspartate formation markedly decreased, but complete oxidation of glutamine carbons to CO2 increased to 37% and 23%, respectively, in resting and proliferating cells. The dipeptide, glycyl-L-glutamine, which is more stable than free glutamine, can substitute for glutamine in thymocyte cultures at higher concentrations.
Brand
K
K
Institute of Biochemistry, Medical Faculty, University of Erlangen-Nuremberg, FRG.
Fekl
W
W
von Hintzenstern
J
J
Langer
K
K
Luppa
P
P
Schoerner
C
C
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002455:Cell Division; D002952:Citric Acid Cycle; D004151:Dipeptides / Q000378:metabolism; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004151:Dipeptides; D005971:Glutamates; D007656:Ketoglutaric Acids; D005973:Glutamine; D002245:Carbon Dioxide; D001224:Aspartic Acid; D018698:Glutamic Acid; C046223:N-glycylglutamic acid; D000641:Ammonia; D005969:Glutamate Dehydrogenase