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Abstract #2612

Anaplerotic Flux Into Citric Acid Cycle 4-Carbon Intermediates is Phenotypically Increased in a Murine Model of Heart Failure

Aslan Turer1, Thomas Gillette1, Shawn Burgess2, Craig Malloy2, and Matthew Merritt3

1Cardiology, UT Southwestern Medical Center, Dallas, TX, United States, 2AIRC, UT Southwestern Medical Center, Dallas, TX, United States, 3Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States

Heart failure (HF) was studied using a murine model of aortic constriction. Hearts were perfused to steady state using [1,6-13C2]glucose, [1,3-13C2]acetoacetate, and [U-13C]fatty acids. Substrate selection for acetyl-CoA production was measured using isotopomer analysis by carbon-13 NMR. A standard model which includes oxidative flux as well as pyruvate anaplerosis (YPC) via pyruvate carboxylase or the malic enzyme was evaluated. Inconsistencies in the fits led to proposal of a more complicated model that also includes anaplerosis through the succinyl-CoA pathway (Ys), leading to significantly better fits. We hypothesize that induction of the Ys anaplerotic pathway is phenotypic of HF.

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