Abstract #0054

Both the Glutaminolytic & Reverse Isocitrate Dehyrdogenase Pathways are Important for De Novo Lipogenesis from Glutamine in Immortilized Hematapoietic Cells

Anthony Mancuso^1,2, Kathryn E. Wellen¹, Chao Lu¹, Weixia Liu, Stephen Pickup, Craig B. Thompson^1,3

¹Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA; ²Radiology, University of Pennsylvania, Philadelphia, PA, USA Minor Outlying Islands; ³Memorial Sloan Kettering Cancer Center, New York, NY, USA

We have been studying lipogenesis because of its importance in mammalian cell growth and proliferation. Glucose is normally the primary precursor for this process; however, we have observed that human glioblastoma cells derive much lipogenic carbon from glutamine. In this work, we report that immortalized hematopoietic cells produce lipid from glutamine via both the glutaminolytic and reverse isocitrate dehydrogenase (IDH) pathways in the presence of glucose. In the absence of glucose, the more energy efficient glutaminolytic pathway was predominant. These results are fundamentally different from those observed for glioblastoma cells, which predominantly use the more energy inefficient reverse IDH pathway, perhaps compromising efficiency for the sake of rapid biosynthesis.