Effect of Branched-Chain Alpha-Keto Acid Dehydrogenase Depletion on Myotube Protein Metabolism

Branched-chain amino acids (BCAAs) are essential amino acids that are crucial for skeletal muscle anabolism. Compared to the effects of these amino acids on skeletal muscle, much less is known on how impairment in BCAA catabolism affects this tissue. BCAA catabolism starts with the reversible transamination by the mitochondrial enzyme branched-chain aminotransferase 2 (BCAT2). This is followed by the irreversible decarboxylation, catalyzed by branched-chain -keto acid dehydrogenase (BCKD) complex. Our lab has previously shown that BCAT2 and BCKD catabolic activities are essential for the differentiation of skeletal myoblasts into myotubes in vitro. Here, we investigate the effect of depletion of BCAT2 or BCKD in differentiated myotubes. We demonstrate that disrupting BCAT2 negatively affects myotube survival. Furthermore, we show that BCKD depletion augments myofibrillar protein content and increases mTORC1 signaling in myotubes. Conclusively, interventions that target BCKD abundance or functions may promote muscle protein anabolism in individuals with muscle wasting conditions