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. 2021 Jan 29;22(3):1350. doi: 10.3390/ijms22031350

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Effects of methotrexate (MTX) on endogenous and exogenous formate utilization. (a) The upper panel shows the percent changes of the enrichments in deoxyadenosine, deoxyguanosine, deoxythymidylate (dTMP), methionine, serine in cells treated with MTX. Endogenous and exogenous formate utilization were traced by L-[3-¹³C]serine (in orange) and exogenous [¹³C]formate (in pink). MTX decreased the incorporations of 1C moiety from L-[3-¹³C]serine (endogenous formate) and increased that from exogenous [¹³C]formate. The percent changes shown in the arrows indicate the isotopic enrichments in each target compound compared to controls. (b) The lower panel summarizes the metabolic fate of 1C flow from serine and formate. Solid arrows represent increased metabolic fluxes and dashed arrows represent decreased metabolic fluxes after MTX treatment.

Effects of methotrexate (MTX) on endogenous and exogenous formate utilization. (a) The upper panel shows the percent changes of the enrichments in deoxyadenosine, deoxyguanosine, deoxythymidylate (dTMP), methionine, serine in cells treated with MTX. Endogenous and exogenous formate utilization were traced by L-[3-¹³C]serine (in orange) and exogenous [¹³C]formate (in pink). MTX decreased the incorporations of 1C moiety from L-[3-¹³C]serine (endogenous formate) and increased that from exogenous [¹³C]formate. The percent changes shown in the arrows indicate the isotopic enrichments in each target compound compared to controls. (b) The lower panel summarizes the metabolic fate of 1C flow from serine and formate. Solid arrows represent increased metabolic fluxes and dashed arrows represent decreased metabolic fluxes after MTX treatment.