Limitations of Zilversmit approach to analysis of precursor-product relationships

Recently, a modification of the Zilversmit method has been used to establish the extent to which a precursor-product relationship exists between the phospholipids of the lamellar bodies (PLlb) and those in the alveolar compartment (PLalv) of the rabbit lung. According to this analysis, if a plot of specific activity (sp act) of PLalv vs. the integral with respect to time of (sp act PLlb-sp act PLalv) results in a straight line, then a presumptive precursor-product relationship exists; the slope of this line will indicate the turnover time of the product compartment. We have established analytically and confirmed numerically that collinearity is, in fact, a poor test of precursor-product relationship. We examine some causes of hysteresis and the direction of hysteresis of this plot for compartmental configurations other than precursor product. Finally, we apply the conclusions of our analysis to some of the published data relating to the relationship between PLlb and PLalv, and we indicate where previous conclusions may now be considered premature.