Branched-Chain Keto Acid Dehydrogenase Kinase Depletion Affects Branched-Chain Alpha-Keto Acid Dehydrogenase Activity and Muscle Cell Differentiation
Beatty, Brendan Eamon
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Branched-chain amino acids are indispensible amino acids that are known for having anabolic effects in skeletal muscle. These effects BCAAs elicit in existing skeletal muscle are well documented in literature. However, much less is known about how they affect the process of myogensis and muscle regeneration. Data generated in our lab have shown that the intact BCAA catabolic pathway is required for proper skeletal muscle cell differentiation. In the current study, the main enzymes involved in the catabolism of BCAAs were assessed, in addition to the activity of the rate-limiting enzyme (Branched-chain -ketoacid dehydrogenase - BCKD) in the pathway. Increasing the flux of BCAAs through this pathway via siRNA mediated knockdown of a negative regulator of the pathway augmented differentiation. It is evident that BCAA catabolism is intricately involved in the process of muscle cell differentiation. Further study into the regulation of BCAA catabolism during differentiation is warranted; to aid in the development of nutritional based interventions for populations suffering from muscle wasting condition.