Estimating the fractional synthetic rate of plasma apolipoproteins and lipids from stable isotope data

The use of isotopic tracer studies to quantitate parameters characterizing apolipoprotein metabolism is enjoying a resurgence. This is due in large part to the availability of a number of stable isotopes and methods to measure them accurately in small quantities. Most experimental protocols in which stable isotopes are used call for endogenous labeling of the apolipoprotein of interest by an infusion of a labeled amino acid. Unlike the radioactively labeled amino acid counterpart in which turnover studies have traditionally been carried out for 72 hours to 14 days, the duration of the stable isotope experiment is normally less than 24 hours. This has contributed to some problems related to estimating the kinetic parameters because simplistic formulas whose underlying assumptions are not applicable to the lipoprotein system under study are often invoked. This is particularly true for the fractional synthetic rate (FSR). The purpose of this review is to address some of these problems. We derive the formula commonly used to estimate the FSR. In so doing, the underlying assumptions are carefully delineated. We then discuss several ways in which the formula is applied. Finally, we discuss the implications of these assumptions when the formula is applied to specific lipoprotein systems.