Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate.

ABSTRACT:

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 (13)C-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

SUBMITTER: Kamphorst JJ 

PROVIDER: S-EPMC4322440 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature