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Simple Esterification of [1-13C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production.


ABSTRACT: Alpha-ketoglutarate (α-KG) is a key metabolite and signaling molecule in cancer cells, but the low permeability of α-KG limits the study of α-KG mediated effects in vivo. Recently, cell-permeable monoester and diester α-KG derivatives have been synthesized for use in vivo, but many of these derivatives are not compatible for use in hyperpolarized carbon-13 nuclear magnetic resonance spectroscopy (HP-13C-MRS). HP-13C-MRS is a powerful technique that has been used to noninvasively trace labeled metabolites in real time. Here, we show that using diethyl-[1-13C]-α-KG as a probe in HP-13C-MRS allows for noninvasive tracing of α-KG metabolism in vivo.

SUBMITTER: AbuSalim JE 

PROVIDER: S-EPMC9107957 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Simple Esterification of [1-<sup>13</sup>C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production.

AbuSalim Jenna E JE   Yamamoto Kazutoshi K   Miura Natsuko N   Blackman Burchelle B   Brender Jeffrey R JR   Mushti Chandrasekhar C   Seki Tomohiro T   Camphausen Kevin A KA   Swenson Rolf E RE   Krishna Murali C MC   Kesarwala Aparna H AH  

ACS chemical biology 20210923 11


Alpha-ketoglutarate (α-KG) is a key metabolite and signaling molecule in cancer cells, but the low permeability of α-KG limits the study of α-KG mediated effects in vivo. Recently, cell-permeable monoester and diester α-KG derivatives have been synthesized for use in vivo, but many of these derivatives are not compatible for use in hyperpolarized carbon-13 nuclear magnetic resonance spectroscopy (HP-<sup>13</sup>C-MRS). HP-<sup>13</sup>C-MRS is a powerful technique that has been used to noninvas  ...[more]

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