Jacquelyn M Walejko, Bridgette A Christopher, Scott B Crown, Guo-Fang Zhang, Adrian Pickar-Oliver, Takeshi Yoneshiro, Matthew W Foster, Stephani Page, Stephan van Vliet, Olga Ilkayeva, Michael J Muehlbauer, Matthew W Carson, Joseph T Brozinick, Craig D Hammond, Ruth E Gimeno, M Arthur Moseley, Shingo Kajimura, Charles A Gersbach, Christopher B Newgard, Phillip J White, Robert W McGarrah
Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly-13 C-labeled α-ketoisovalerate ([U-13 C]KIV) in the heart is reamination to valine. Activation of cardiac branched-chain α-ketoacid dehydrogenase (BCKDH) by treatment with the BCKDH kinase inhibitor, BT2, does not impede the strong flux of [U-13 C]KIV to valine. Sequestration of BCAA and BCKA away from mitochondrial oxidation is likely due to low levels of expression of the mitochondrial BCAA transporter SLC25A44 in the heart, as its overexpression significantly lowers accumulation of [13 C]-labeled valine from [U-13 C]KIV...
March 15, 2021: Nature Communications