Glutaminolysis: supplying carbon or nitrogen or both for cancer cells?
A cancer cell comprising largely of carbon, hydrogen, oxygen, phosphorus, nitrogen and sulfur requires not only glucose, which is avidly transported and converted to lactate by aerobic glycolysis or the Warburg effect, but also glutamine as a major substrate. Glutamine and essential amino acids, such as methionine, provide energy through the TCA cycle as well as nitrogen, sulfur and carbon skeletons for growing and proliferating cancer cells. The interplay between utilization of glutamine and glucose is likely to depend on the genetic make-up of a cancer cell. While the MYC oncogene induces both aerobic glycolysis and glutaminolysis, activated β-catenin induces glutamine synthesis in hepatocellular carcinoma. Cancer cells that have elevated glutamine synthetase can use glutamate and ammonia to synthesize glutamine and are hence not addicted to glutamine. As such, cancer cells have many degrees of freedom for re-programming cell metabolism, which with better understanding will result in novel therapeutic approaches.
Dang
Chi V
CV
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cvdang@jhmi.edu
D000596:Amino Acids / Q000378:metabolism; D002244:Carbon / Q000378:metabolism*; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
D000596:Amino Acids; D016271:Proto-Oncogene Proteins c-myc; D005973:Glutamine; D018698:Glutamic Acid; D002244:Carbon; D005947:Glucose; D009584:Nitrogen