The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase
Open accessAbstract
SUMMARY A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium; HPLM). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent is an inhibition of de novo pyrimidine synthesis – an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits UMP synthase and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.
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Metadata
- Authors
- Cantor, J. R., Abu-Remaileh, M., Kanarek, N., Freinkman, E., Gao, X., Louissaint, A., Lewis, C. A., & Sabatini, D. M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 169
- Issue
- 2
- Pages
- 258-272.e17
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2604353006
- Cited by
- 616
- References
- 74
- FWCI
- 14.07
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Cantor, J. R., Abu-Remaileh, M., Kanarek, N., Freinkman, E., Gao, X., Louissaint, A., Lewis, C. A., & Sabatini, D. M. (2017). Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase. Cell. https://doi.org/10.1016/j.cell.2017.03.023
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