Abstract #3610

Metabolism of Hyperpolarized Pyruvate detects Knockout of Pyruvate Dehydrogenase Kinase

Gaurav Sharma¹, Cheng Yang Wu², R. Max Wynn^2,3, David T. Chuang^2,3, Craig R. Malloy^1,3, Chalermchai Khemtong¹, and A. Dean Sherry^1,4

¹Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, United States, ³Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States, ⁴Chemistry, University of Texas at Dallas, Dallas, TX, United States

The Pyruvate Dehydrogenase Complex (PDC) plays a critical role in the regulation of carbohydrate metabolism. Pyruvate Dehydrogenase Kinase (PDK) inhibits PDC via phosphorylation making it a novel therapeutic target for metabolic diseases. The present study aimed to evaluate whether the metabolism of HP-13C pyruvate is sensitive to PDK inhibition. Our results showed that higher production of HP-bicarbonate via PDC in PDK deficient livers. ¹³C NMR isotopomer analysis of tissue extracts confirms higher 13C-enrichment of AcCo-A in the DKO livers than the control group. The result suggested that the appearance of HP-bicarbonate is a sensitive biomarker for monitoring the consequences of PDK inhibition.

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