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Abstract #4049

Enhanced Kinetic Analysis of Hyperpolarized Pyruvate Metabolism in Cancer Cells Identifies a Compensatory Pathway Supplied by Glutamine

Lloyd Lumata 1 , Chendong Yang 2 , Bookyung Ko 2 , Ralph J. Deberardinis 2 , and Matthew E Merritt 1

1 AIRC, UTSW Medical Center, Dallas, TX, United States, 2 Children's Med. Ct. Res. Inst., UTSW Med. Ctr., Dallas, TX, United States

Glutamine metabolism can satisfy both energetic and biosynthetic demands of cancer cells. Glutamine oxidation can be accentuated when glucose metabolism is blocked by any intervention. Here the action of an inhibitor of mitochondrial pyruvate transport is studied with hyperpolarized (HP) pyruvate. The inhibitor blocked formation of HP alanine and bicarbonate in a glioblastoma cell line while leaving lactate formation largely unperturbed. Further analysis showed that when pyruvate transport is inhibited glutamate dehydrogenase is upregulated, resulting in increased glutamine oxidation.

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