Fig. 2

Metabolism of branched chain amino acids (BCAAs) and ketones. a BCAAs consist of valine, leucine and isoleucine. The metabolic homeostasis of BCAAs is controlled by a series of BCAA catabolic including branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). As the rate-limiting enzyme of BCAA degradation, activity of BCKDH is regulated by phosphorylation/inactivation via BCKDH-kinase (BCKD), while dephosphorylated and activated by a mitochondrion-localized protein phosphatase-2C. BCAAs are converted to acetyl CoA, which enters the tricarboxylic acid cycle (TCA) and electron transport chain (ETC) to generate ATP. b Ketone bodies are produced predominantly in the liver through ketogenesis, as the form of acetone, β-hydroxybutyrate and acetoacetate. The later two are the the main ketones circulating in the blood and transported to heart for oxidation. Once ketones enter the cardiomyocytes and be transported to the mitochondrial matrix, β-hydroxybutyrate and acetoacetate is oxidized into acetyl-CoA by β-hydroxybutyrate-dehydrogenase (BDH) and succinyl-CoA:3-oxoacid-CoA-transferase (SCOT). Acetyl CoA enters TCA and ETC to generate ATP