Schoors, S. et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520, 192–197 (2015).
It’s not every day that scientists discover something entirely unexpected. Oftentimes, researchers know the results they are going to obtain when they write a grant. This way, they can prove that their research is both high impact and also feasible which goes a long way in the grant writing community. When researchers are able to discover something new and unanticipated, it is often no surprise that their findings end up in a high impact journal such as Nature or Science.
One such paper published in 2015 did just that. The researchers discovered that the enzyme CPT1A was rate limiting in the oxidation of fatty acids and caused vascular sprouting defects due to impaired proliferation. The researchers were interested in determining why knocking out this enzyme had such an effect on proliferation.
They started with the obvious culprits, that the metabolites of fatty acid oxidation, acetyl CoA, were fed into glucose metabolism to make ATP. Data showed that knocking out the CPT1A protein did not lower the ATP levels in the cell or change the ADP/ATP ratio. Additionally, the cells were not in energy stress and were in redox balance.
Knowing that the fatty acid oxidation products did not onto provide the energy for the proliferation of endothelial cells, the researchers chose to isotopically label the fatty acids with carbon-13. This allowed them to easily see where the carbons ended up. To their surprise, the fatty acid carbons ended up incorporating into deoxyribonucleotides.
This is a truly incredible finding as so far it seems that only endothelial cells use fatty acid carbons in this way. Looking forward toward the future, the authors have found that their work holds implications in the treatment of retinopathy diseases in premature newborns. This article is of special interest to our BCM441 class because it highlights how metabolites of macromolecules can enter many pathways.
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