The computation of saturable and linear components of intestinal and other transport kinetics

Abstract

1. Published data for absorption kinetics have been fitted by non-linear regression to (i) a single Michaelis-Menten function, (ii) a Michaelis-Menten function plus a linear term and (iii) a sum of two Michaelis-Menten functions. A series of criteria have been drawn up to establish the goodness of fit in each case. 2. In 17 out of 35 cases the Michaelis-Menten function was the "best fit". In nine cases the "best-fit" model also included a linear term, but never was the sum of two Michaelis-Menten functions accepted to be the "best-fit" model. 3. Linearity of a Lineweaver-Burk plot was of unreliable diagnostic value in assessing goodness of fit. 4. Since the fit of a Michaelis-Menten function was often poor, simulated data sets with error were used to study the influence of experimental design etc. on Michaelis-Menten parameter estimation. 5. Precision of estimation of Km is increased by increasing the number of data points, reducing their variance, increasing the data range and by straddling Km in the observations. For a given constant number of observations there is no advantage in using replicate observations at few concentrations or single values at relatively many concentrations, or in using single values rather than means. 6. The caution necessary in interpretation of kinetic models is emphasized.