Investigation of the role of branched chain amino add on stimulation of protein synthesis and application for preservation and improvement of muscle mass

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Branched-chain amino acid Ieucine has been shown to activate the protein translational regulators. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the ranched-chain α-keto acid dehydrogenase (BCKDH) complex. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The results demonstrated that knockdown of the BCKDH E2 subunit expression, presumably abolishing the BCKDH complex activity, increased the effect of leucine on phosphorylation of p70S6K, a key regulatory protein involved in the initiation of mRNA translation. On the contrary, activation of BCKDH complex by trancfection of kinase-siRNA decreased the leucine's effect. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex. It has been reported that BCKDH activity in liver has gender difference. So we investigated the leucine-induced activation of the protein translation initiation in male and female rats. Leucien-induced activation of the translation initiation in skeletal muscle was increased both in male and female rats at the end of light period (hepatic BDKCH activity is higher in male rats than female rats). In contrast, leucine-induced activation of the translation initiation in skeletal muscle was higher in male rats than female rats after the 18 h starvation (hepatic BCKDH is inactivated both in male and female rats). These results suggest that gender difference in leucine-induced activation of the protein translation initiation in skeletal muscle is not related to the activity of hepatic BCKDH. Further studies are needed to elucidate the gender difference in leucine-induced activation of the protein translation initiation.