Hyperpolarized [1- <sup>13</sup> C]pyruvate-to-[1- <sup>13</sup> C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane
Yi Rao, Seth T. Gammon, Niki M. Zacharias, Tracy Liu, Travis C. Salzillo, Yuanxin Xi, Jing Wang, Pratip K. Bhattacharya, David Piwnica‐Worms
Abstract
Significance Hyperpolarized [1- 13 C]pyruvate magnetic resonance spectroscopic imaging (MRSI), which measures [1- 13 C]pyruvate-to-[1- 13 C]lactate conversion, has been widely explored as a metabolic-imaging modality interpreted to reflect LDHA activity and glycolytic flux. However, we show definitively that hyperpolarized [1- 13 C]pyruvate-to-[1- 13 C]lactate conversion rates are primarily a functional readout of [1- 13 C]pyruvate transmembrane influx mediated by MCT1, providing a mechanistic reinterpretation and redirection of clinical translation.
Topics & Concepts
ChemistryGlycolysisMonocarboxylate transporterTransmembrane proteinTransporterFlux (metallurgy)BiochemistryMetabolismOrganic chemistryGeneReceptorAdvanced NMR Techniques and ApplicationsAdvanced MRI Techniques and ApplicationsProtein Structure and Dynamics