Molecular signalling is often used as a surrogate measure for various outputs like glucose uptake and protein synthesis. However in the case of gluocse uptake only 30% of maximal PKB activity is required to saturate GLUT4 translocation (Bilan et al, 2009 - attached). In the case of protein synthesis, 30% of maximal S6K1 phosphorylation associates with saturated protein synthesis (Crozier et al, 2005 http://jn.nutrition.org/content/135/3/376.long
). These data suggest that there is a reserve capacity built into signalling pathways. This raises the question "is this reserve capacity important and physiologically relevant?"
In feeding induced time course studies S6K1 switch off occurs more slowly than the switch off of protein synthesis (Atherton et al, http://ajcn.nutrition.org/content/92/5/1080.long
) and in response to intermittent protein feeding the S6K1 phosphorylation response does not correlate with protein synthesis (Areta et al, 2013 http://www.ncbi.nlm.nih.gov/pubmed/23459753
). Despite the lack of correlation between S6K1 and protein synthesis in response to feeding, the S6K1 response to resistance exericse correlates highly with hypertrophy in response to training (Baar and Esser, 1999 and Terzis et al, 2008) suggesting that it is a good read out of growth. What is the function of the residual S6K1 activity and why isn't there a correlation between S6K1 and feeding induced protein synthesis? Is this a feedforward mechanism?
How do we begin to reconcile the discordant data and do we need to develop new theories and methods to assess the molecular control of muslce metabolism and growth?