Comparison of mass isotopomer dilution methods used to compute VLDL production in vivo

The recent development of mass isotopomer distribution methods represents an important new tool for quantifying synthetic rates. These methods allow precursor enrichment to be determined indirectly from the enrichment of the product, thus sidestepping the often difficult problem of measuring the precursor enrichment. Two different methods have been described to compute synthetic rates by this general approach in the laboratories of M. K. Hellerstein and J. K. Kelleher, and variations of these basic approaches have also been presented by W. N. Lee and by ourselves. A comparison between the different methods has never been reported. In this paper, we take a specific application, calculation of the fractional rate of incorporation of acetyl-CoA into very low density lipoprotein-bound palmitate, and compare the results obtained from all of the mass isotopomer methods using the same data set obtained in vivo in human subjects. We found that it is critical that the measured background isotopomer distribution of palmitate is used rather than the theoretical background isotopomer distribution. We also found that the different methods give comparable precursor enrichments and comparable fractional synthesis rates, provided that the enrichments in Kelleher's method are properly weighted. Thus the choice of method to use is a matter of personal preference.