Effect of the leucine analogs, α‐ketoisocaproic acid (KIC) and norleucine, on muscle protein synthesis and translation initiation factor activation in neonatal pigs

Leucine acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonatal pigs; however, the chemical structure responsible for this effect has not been identified. We have shown that isoleucine and valine are not able to stimulate protein synthesis when raised in plasma within the physiological postprandial range. The current study evaluated the effect of leucine, KIC and norleucine infusion (0 or 400 μmol·kg −1 ·h −1 for 60 min) on protein synthesis and activation of translation initiation factors. Infusion of leucine, KIC and norleucine raised plasma levels of each compound compared to controls. In addition, KIC increased (P < 0.01) and norleucine reduced (P < 0.02) plasma levels of leucine compared to controls. Administration of leucine and KIC increased the phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein‐1 (4E‐BP1, P < 0.01) and decreased the inactive 4E BP1·eIF4E complex in longissimus dorsi muscle. Protein synthesis was increased (P < 0.02) in muscle with infusion of leucine and KIC. Norleucine infusion did not affect muscle protein synthesis or translation initiation factor activation. In liver, neither protein synthesis nor activation of translation initiation factors was affected by any treatment. Results suggest that the ability of leucine to act as a nutrient signal to stimulate protein synthesis is likely specific for leucine or its metabolites. (NIH AR 44474 and USDA 58‐6250‐6‐001)