Regulation of protein synthesis by amino acids in muscle of neonates

Abstract

The marked increase in skeletal muscle mass during the neonatal period is largely due to a high rate of postprandial protein synthesis that is modulated by an enhanced sensitivity to insulin and amino acids. The amino acid signaling pathway leading to the stimulation of protein synthesis has not been fully elucidated. Among the amino acids, leucine is considered to be a principal anabolic agent that regulates protein synthesis. mTORC1, which controls protein synthesis, has been implicated as a target for leucine. Until recently, there have been few studies exploring the role of amino acids in enhancing muscle protein synthesis in vivo. In this review, we discuss amino acid-induced protein synthesis in muscle in the neonate, focusing on current knowledge of the role of amino acids in the activation of mTORC1 leading to mRNA translation. The role of the amino acid transporters, SNAT2, LAT1, and PAT, in the modulation of mTORC1 activation and the role of amino acids in the activation of putative regulators of mTORC1, i.e., raptor, Rheb, MAP4K3, Vps34, and Rag GTPases, are discussed.

Figure 1

Fractional rates of protein synthesis in longissimus dorsi (LD) muscle of 6- and 26-day-old pigs in response to euinsulinemic-euglycemic-euaminoacidemic conditions (C), euinsulinemic-euglycemic-hyperaminoacidemic clamps (AA), and hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS) (panel A). Fractional rates of protein synthesis in LD muscle of 6-day-old pigs in response to individual infusion of the branched-chain amino acids, leucine (Leu), isoleucine (Iso) and valine (Val), in comparison with saline (sal)/control (panel B). Values are means ± SEM, means with different letters differ at P < 0.05.

Figure 2

Recent concepts of the insulin- and amino acid-induced activation of mTORC1.

Figure 3

The regulation of leucine transport by glutamine leading to the activation of mTORC1 and protein synthesis.

Figure 4

The molecular model of amino acid-induced activation of mTORC1 and protein synthesis by PAT2.

Figure 5

Fractional rates of protein synthesis (A), raptor-mTOR interaction (B), S6K1 phosphorylation (C) and 4E-BP1 phosphorylation in longissimus dorsi (LD) muscle of 7-day-old pigs after 60 min of infusion of saline (Sal), 400 μmol·kg⁻¹·h⁻¹ leucine (Leu), and leucine with rapamycin (Leu+Rap). Values are means ± SEM; means with different letters differ at P < 0.05.

Figure 6

The regulation of protein synthesis by amino acids and insulin.