Department of Medicine, Division of Endocrinology, Augusta University, Augusta, GA 30912, USA.
Department of Physical Therapy, Augusta University, Augusta, GA 30912, USA.
Int J Mol Sci. 2024 Jul 11;25(14):7601. doi: 10.3390/ijms25147601.
Muscle wasting can be caused by nutrition deficiency and inefficient metabolism of amino acids, including Branched Chain Amino Acids (BCAAs). Branched Chain Amino Acids are a major contributor to the metabolic needs of healthy muscle and account for over a tenth of lean muscle mass. Branched chain alpha-ketoacid dehydrogenase (BCKD) is the rate limiting enzyme of BCAA metabolism. Inhibition of BCKD is achieved through a reversible phosphorylation event by Branched Chain a-ketoacid dehydrogenase kinase (BCKDK). Our study set out to determine the importance of BCKDK in the maintenance of skeletal muscle. We used the Gene Expression Omnibus Database to understand the role of BCKDK in skeletal muscle pathogenesis, including aging, muscular disease, and interrupted muscle metabolism. We found BCKDK expression levels were consistently decreased in pathologic conditions. These results were most consistent when exploring muscular disease followed by aging. Based on our findings, we hypothesize that decreased BCKDK expression alters BCAA catabolism and impacts loss of normal muscle integrity and function. Further research could offer valuable insights into potential therapeutic strategies for addressing muscle-related disorders.
肌肉减少症可能由营养缺乏和氨基酸代谢效率低下引起，包括支链氨基酸（BCAAs）。支链氨基酸是健康肌肉代谢需求的主要贡献者，占去脂肌肉质量的十分之一以上。支链α-酮酸脱氢酶（BCKD）是 BCAA 代谢的限速酶。BCKD 的抑制是通过支链α-酮酸脱氢酶激酶（BCKDK）的可逆磷酸化事件实现的。我们的研究旨在确定 BCKDK 在维持骨骼肌中的重要性。我们使用基因表达综合数据库来了解 BCKDK 在骨骼肌发病机制中的作用，包括衰老、肌肉疾病和肌肉代谢中断。我们发现 BCKDK 的表达水平在病理条件下持续下降。当探索肌肉疾病继之衰老时，这些结果最为一致。基于我们的发现，我们假设 BCKDK 表达的降低改变了支链氨基酸的分解代谢，并影响了正常肌肉完整性和功能的丧失。进一步的研究可能为解决与肌肉相关的疾病的潜在治疗策略提供有价值的见解。
