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Amino Acid Metabolite Infusion Enhances Muscle Protein Synthesis without Altering Degradation in Neonates
Author(s) -
Wheatley Scott Michael,
ElKadi Samer,
Suryawan Agus,
Boutry Claire,
Orellana Renan,
Nguyen Hanh,
Davis Steve,
Davis Teresa
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.244.2
Subject(s) - amino acid , protein biosynthesis , medicine , chemistry , protein degradation , endocrinology , leucine , skeletal muscle , p70 s6 kinase 1 , metabolite , phosphorylation , biochemistry , protein kinase b
Many low‐birth‐weight infants experience failure to thrive. The amino acid, leucine, stimulates protein synthesis in skeletal muscle of the neonate but less is known about the effects of amino acid metabolites on neonatal muscle protein synthesis. The study objective was to determine the effect of an amino acid metabolite (AAM) on fractional protein synthesis, translation initiation, and regulation of the degradation pathway. Overnight fasted neonatal pigs were infused with AAM at 0, 20, 100, or 400 μmol·kg −1 ·hr −1 (AAM 0, AAM 20, AAM 100, and AAM 400) for 1 h. Blood AAM concentrations increased with AAM infusion ( P <0.05) and were 10, 98, 316, and 1400 nmol·ml −1 . Fractional protein synthesis rates in the longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles increased in response to AAM 20 ( P <0.05) but AAM 100 affected only the LD while AAM 400 had no effect. Infusion of 20 and 100 AAM increased ( P <0.05) formation of the active eIF4E · eIF4G complex as well as phosphorylation of S6K1 and 4EBP1 in the LD, gastrocnemius, and soleus. Infusion of 20, but not 100, AAM increased ( P <0.05) the activation of these mTORC1 indices in the diaphragm. Expression of Atrogin‐1, MURF1, and LC3‐ II, markers of protein degradation were unchanged. Results suggest that supplemental AAM enhances protein synthesis in skeletal muscle of the neonate by stimulating translation initiation.