A model of whole-body protein turnover based on leucine kinetics in rodents

Abstract

The measurement of fractional synthesis rate is based on the following assumptions: amino acids for protein synthesis are supplied by an intracellular pool; amino acids from protein degradation are not recycled preferentially to protein synthesis; and proteins turn over at a homogeneous rate. To test these assumptions, a mechanistic, theoretical model of protein turnover for a nongrowing 26-g mouse was developed on the basis of data from the literature. The model consisted of three protein pools turning over at fast (102 μmol Leu, t 1/2 = 11.5 h), medium (212 μmol Leu, t (1/2) = 16.6 h) or slow (536 μmol Leu, t(1/2) = 71.5 h) rates and extracellular (1.69 μmol Leu), leucyl-tRNA (0.0226 μmol Leu) and intracellular (5.72 μmol Leu) amino acid pools that exchanged amino acids. The flow of amino acids from the protein pools to the leucyl-tRNA pool determined the amount of recycling. The flow of amino acids from the extracellular pool to aminoacyl tRNA determined the amount of channeling. Two flooding dose data sets were used to evaluate specific radioactivity changes predicted by the model. Predictions of specific radioactivities using flooding dose, pulse dose or continuous infusion methods indicated that the model can be a useful tool in estimating the rates of channeling and recycling. However, it was found that use of data from flooding dose experiments might cause inaccurate predictions of certain fluxes.