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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Jurre J Kamphorst, Michelle K Chung, Jing Fan, Joshua D Rabinowitz

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 50% to 80%. Thus, under hypoxia, one or more additional substrates significantly contribute to acetyl-CoA production. (13)C-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 μM). CONCLUSIONS: Acetate is an important source of acetyl-CoA in hypoxia. Inhibition of acetate metabolism may impair tumor growth. More... »

PAGES

23

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/2049-3002-2-23

DOI

http://dx.doi.org/10.1186/2049-3002-2-23

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030230764

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25671109


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