Branched-chain α-keto acid dehydrogenase kinase (BCKDK) phosphorylates and inhibits branched-chain α-keto acid dehydrogenase, while its activation is facilitated by dephosphorylation mediated by the phosphatase PPM1K, also known as PP2Cm ( 13). The activity of the BCKDH complex is tightly regulated through mechanisms of phosphorylation and dephosphorylation, as demonstrated by various studies ( 5, 7, 9– 12). These BCαKAs subsequently undergo an irreversible decarboxylation process mediated by the enzyme complex BCKDH. The initiation of branched-chain amino acids (BCAAs) metabolism involves a reversible transamination process catalyzed by the enzyme BCAT2 within the mitochondria, resulting in the formation of branched-chain α-keto acids (BCαKAs). The initial metabolism of BCAAs takes place in extrahepatic tissues through enzymatic reactions involving isoleucine, leucine, and valine, with these metabolic pathways being conserved among eukaryotes ( 11). Notably, the liver, pancreas, skeletal muscles, kidneys, and brown adipose tissue also play essential roles in BCAA protein synthesis ( 10). Tracer studies in mice have demonstrated that the oxidation of BCAAs primarily occurs in skeletal muscles, brown adipose tissue, liver, kidneys, and heart. Metabolic pathways and regulation of branched-chain amino acids Through this comprehensive exploration, we aim to contribute to a deeper understanding of BCAAs’ therapeutic potential in the context of heart failure. Additionally, this paper explores the potential application, feasibility, and significance of harnessing BCAAs and their metabolism in the treatment of HF. This paper aims to fill this gap by providing a concise overview of the current research progress on the physiological and pathophysiological processes related to BCAAs in HF. However, further investigation is necessary to precisely determine the functional role of BCAAs in HF. Notably, several studies have revealed a significant association between BCAAs and heart failure (HF), encompassing aspects of its progression, severity, and prognosis. As advancements in amino acid research shed light on BCAAs’ roles, some studies propose that beyond being dietary nutrients, BCAAs may also contribute to regulating specific diseases. These roles highlight BCAAs’ multifaceted impact on various physiological functions. These processes encompass the maintenance of blood glucose balance, facilitation of protein synthesis, modulation of insulin resistance, and regulation of pathways associated with nutrient sensitivity ( 2– 9). Serving as both signaling molecules and regulators, BCAAs play a pivotal role in diverse physiological processes. Leucine (Leu), isoleucine (Ile), and valine (Val) constitute essential branched-chain amino acids (BCAAs), acquired solely through dietary consumption ( 1– 5). In conclusion, this article elucidates the multifaceted roles of BCAAs in heart failure and cardiovascular health, providing guidance for future research and intervention measures. BCAAs and their metabolites are also considered as biomarkers for evaluating cardiac metabolic risk.

Furthermore, the article discusses therapeutic strategies, assesses the impact of BCAAs on cardiac dysfunction, and examines the potential of modulating BCAAs metabolism as a treatment for heart failure. This article explores intricate metabolic pathways, unveiling the connection between disrupted BCAAs metabolism and the progression of heart failure. However, disrupted BCAAs metabolism has been associated with conditions such as hypertension, obesity, and atherosclerosis. Simultaneously, branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, play significant roles in blood glucose regulation, protein synthesis, and insulin sensitivity. Researchers are currently focusing their efforts on investigating the metabolism of carbohydrates, fatty acids, and amino acids to enhance the prognosis of cardiovascular diseases. 2Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaĪs a terminal stage of various cardiovascular diseases, heart failure is of great concern due to its high mortality rate and limited treatment options.1Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed by the Province and Ministry, Guangxi Medical University, Nanning, China.

What are branch chained amino scids