Kinetics of galactose uptake by perfused rat livers: applicability of a family of models.

Mathematical models for general substrate uptake mechanisms in the liver have been used to describe the kinetics of galactose removal. In this study sets of galactose uptake rates to galactose concentration relations obtained by perfusion of ten livers of 200 g rats were examined. The rate of galactose uptake (v) was related to the galactose concentration in the sinusoids (calculated as the logarithmic mean of in- and outlet concentration, ĉ). In all experiments a saturation pattern emerged, but the resulting 1/v versus 1/ĉ plots were all markedly convex, discarding simple Michaelis-Menten kinetics. Data were therefore examined in the light of a family of kinetic models, including the following modifications: substrate inhibition, porto-systemic shunting, and allosterism. The kinetic constants were assessed by iterative procedures, aiming at linearization of the double reciprocal plots. The two latter models were found to fit the experimental data by entering a shunting of 61% of the hepatic blood flow, or two active sites, respectively. Since this degree of shunting is improbable the results speak in favour of allosterism. The work gives an example of whole-liver kinetic considerations when simple Michaelis-Menten is insufficient.