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Supplement: Protein Metabolism in Response to Ingestion Pattern and Composition of Proteins

Latency, Duration and Dose Response Relationships of Amino Acid Effects on Human Muscle Protein Synthesis¹

Michael J. Rennie^*2, Julien Bohé and Robert R. Wolfe^**

^* Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom, Hospices Civils de Lyon Centre Hospitalier Lyon-Sud, Pierre Bénite, France and ^** Metabolism Unit, Department of Surgery, University of Texas Medical Branch, Shriners Burns Hospital, Galveston, TX 77550

²To whom correspondence should be addressed. E-mail: m.j.rennie{at}dundee.ac.uk.

The components of the stimulatory effect of food on net deposition of protein are beginning to be identified and separated. One of the most important of these appears to be the effect of amino acids per se in stimulating muscle anabolism. Amino acids appear to have a linear stimulatory effect within the range of normal diurnal plasma concentrations from postabsorptive to postprandial. Within this range, muscle protein synthesis (measured by incorporation of stable isotope tracers of amino acids into biopsied muscle protein) appears to be stimulated approximately twofold; however, little further increase occurs when very high concentrations of amino acids (>2.5 times the normal postabsorptive plasma concentration) are made available. Amino acids provided in surfeit of the ability of the system to synthesize protein are disposed of by oxidation, ureagenesis and gluconeogenesis. The stimulatory effect of amino acids appears to be time dependent; a square wave increase in the availability of amino acids causes muscle protein synthesis to be stimulated and to fall back to basal values, despite continued amino acid availability. The relationship between muscle protein synthesis and insulin availability suggests that most of the stimulatory effects occur at low insulin concentrations, with large increases having no effect. These findings may have implications for our understanding of the body’s requirements for protein. The maximal capacity for storage of amino acids as muscle protein probably sets an upper value on the extent to which amino acids can be stored after a single meal.

KEY WORDS: • latency • duration • dose response • insulin • stable isotopes