Nutrient signaling components controlling protein synthesis in striated muscle.

Accretion of muscle mass is dependent upon faster rates of protein synthesis than degradation. When an animal is deprived of dietary protein, loss of body weight and negative nitrogen balance ensue. Likewise, refeeding accelerates protein synthesis and results in resumption of positive nitrogen balance. Amino acids and anabolic hormones both interact to maximally enhance rates of protein synthesis acutely during refeeding through an acceleration of the messenger RNA (mRNA) translation initiation. The review will illuminate the molecular mechanisms responsible for increasing mRNA translation initiation in striated muscle. The hastening of mRNA translation initiation most likely results from a stimulation of mammalian target of rapamycin (mTOR) acting through its downstream effector proteins eukaryotic initiation factors (eIF)4E binding protein1 and possibly eIF4G to enhance assembly of eIF4G with eIF4E and 70-kDa ribosomal S6 kinase1. Amino acids and leucine in particular are as effective as a complete meal in stimulating mRNA translation initiation by targeting these specific signal transduction systems. The physiologic importance lies in the potential ability of amino acids as specific nutrients designed to counteract the accelerated host protein wasting associated with a number of disease entities, including cancer, HIV infection, sepsis, and diabetes, and to improve nutrition to maintain muscle mass in aging populations and ensure muscle growth in neonatal populations.