Inhibition of the mTORC1/NF-κB Axis Alters Amino Acid Metabolism in Human Hepatocytes

Figure 7

Rapamycin inhibits the transamination of glutamate and the decarboxylation of ornithine in hepatocytes. (a) Rapamycin inhibits the transamination between glutamate and α-ketoglutaric acid, to produce oxaloacetate and aspartic acid in cells. The contents of intracellular glutamate, oxaloacetate, α-ketoglutaric acid, and aspartic acid were measured by ELISA. The intracellular glutamate content in the group treated with glutamate was higher than that in the control group, and the glutamate level in the glutamate with the rapamycin group was higher than that in the glutamate alone group, indicating that rapamycin reduced the utilization of glutamate. The intracellular levels of α-ketoglutaric acid increased due to the activity of AST, which was attenuated by rapamycin. Treatment (the values represent the , , , ). (b) Rapamycin inhibits the ornithine decarboxylation necessary to produce putrescine, in cells. The contents of intracellular ornithine and putrescine were measured by HPLC. The intracellular ornithine content in the ornithine-treated group was higher than that in the control, and the ornithine group treated with both ornithine and rapamycin contained higher ornithine levels than those treated with ornithine alone, meaning that rapamycin reduced the utilization of ornithine (the values represent the , , ).

(a)

(b)