Impact of separating amino acids between plasma, extracellular and intracellular compartments on estimating protein synthesis in rodents

Three models representing different separations of amino acid sources were used to simulate experimental specific radioactivity data and to predict pr otein fractional synthesis rate (FSR). Data were from a pulse dose of C-14- U Leu given to a non-growing 20g mouse and a flooding dose of H-3 Phe given to a non-growing 200g rat. Protein synthesis rates estimated using the com bined extracellular and intracellular (Ec + Ic) source pool and extracellul ar and plasma (Ec + Pls) source pool mouse models were 78 and 120% d(-1) in liver, 14 and 16% d(-1) in brain and 15 and 14% d(-1) in muscle. Predicted protein synthesis rates using the Ec + Ic, Ec + Ic + Tr (combined extracel lular, intracellular and aminoacyl tRNA source pool) and Ec + Pis rat model s were 57, 3.4 and 57% d(-1) in gastrocnemius, 58, 71 and 62% d(-1) in gut, 8.3, 8.4 and 7.9% d(-1) in heart, 32, 23 and 25% d(-1) in kidney, 160, 90 and 80% d(-1) in liver, 57, 5.5 and 57% d(-1) in soleus and 56, 3.4 and 57% d(-1) in tibialis. The Ec + Ic + Tr model underestimated protein synthesis rates in mouse tissues (5.0, 27 and 2.5% d(-1) for brain, liver and muscle ) and rat muscles (3.4, 5.5 and 3.4% d(-1) for gastrocnemius, soleus and ti bialis). The Ec + Pls model predicted the mouse pulse dose data best and th e Ec + Ic model predicted the rat flooding dose data best. Model prediction s of FSR imply that identification and separation of the source specific ra dioactivity is critical to accurately estimate FSR.