GLUTAMATE OXIDATION BY TROPHOBLASTS IN-VITRO

Catabolism of uniformly and 1(-14)C-labeled glutamate was investigated in human placental cytotrophoblasts and syncytiotrophoblasts cultured on uncoated plastic or a fibrin matrix. Product-labeling experiments resulted in C-14 incorporation into carbon dioxide and tricarboxylic acid cycle intermediates. C-14 incorporation above background was not detected for the putative products, glutamine, amino acids, glutathione, and protein. Inhibitors of specific metabolic pathways were used to elucidate the routes of glutamate oxidation. Incorporation of C-14 into carbon dioxide from [1-C-14]glutamate was inhibited by the glutamate dehydrogenase inhibitor pyridine-2,6-dicarboxylic acid and the aminotransferase inhibitor aminooxyacetic acid. Production of (CO2)-C-14 was higher for syncytiotrophoblast compared with cytotrophoblast and for cells on uncoated plastic compared with a fibrin matrix. Oxidation of glutamate was unaffected by added glutamine as high as 2 mM. The primary route of glutamate metabolism by placental trophoblast in vitro is oxidation to carbon dioxide utilizing both the transferase and deamination pathways.