Journal
CANCER & METABOLISM
Volume 2, Issue -, Pages -Publisher
BMC
DOI: 10.1186/2049-3002-2-23
Keywords
Acetate; Acetyl-CoA; Cancer metabolism; Fatty acids; Hypoxia; Lipogenesis; Mass spectrometry; Palmitate; C-13-tracing
Categories
Funding
- Hope Funds for Cancer Research Fellow [HFCR-11-03-01]
- Howard Hughes Medical Institute International Student Research Fellow
- NIH [P50GM071508, 1R01CA16359-01A1]
- NATIONAL CANCER INSTITUTE [R01CA163591, P30CA016359] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM071508] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Background: Cell growth requires fatty acids for membrane synthesis. Fatty acids are assembled from 2-carbon units in the form of acetyl-CoA (AcCoA). In nutrient and oxygen replete conditions, acetyl-CoA is predominantly derived from glucose. In hypoxia, however, flux from glucose to acetyl-CoA decreases, and the fractional contribution of glutamine to acetyl-CoA increases. The significance of other acetyl-CoA sources, however, has not been rigorously evaluated. Here we investigate quantitatively, using C-13-tracers and mass spectrometry, the sources of acetyl-CoA in hypoxia. Results: In normoxic conditions, cultured cells produced more than 90% of acetyl-CoA from glucose and glutamine-derived carbon. In hypoxic cells, this contribution dropped, ranging across cell lines from 50% to 80%. Thus, under hypoxia, one or more additional substrates significantly contribute to acetyl-CoA production. 13C-tracer experiments revealed that neither amino acids nor fatty acids are the primary source of this acetyl-CoA. Instead, the main additional source is acetate. A large contribution from acetate occurs despite it being present in the medium at a low concentration (50-500 mu M). Conclusions: Acetate is an important source of acetyl-CoA in hypoxia. Inhibition of acetate metabolism may impair tumor growth.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available