OLEATE UPTAKE KINETICS IN THE PERFUSED-RAT-LIVER ARE CONSISTENT WITH PSEUDOFACILITATION BY ALBUMIN

We measured uptake of a representative free fatty acid, oleate, by the single-pass perfused at liver oleate:albumin molar ratios of 0.01 to 2:1. For each ratio, uptake was studied at albumin concentrations from 50 to 600 mu M. When uptake velocity was plotted as a function of the albumin concentration, the data at each ratio exhibited a pseudosatur ation pattern as previously observed in isolated cells (J Clin Invest 84: 1325). At a physiologic albumin concentration of 600 mu M, a plot of uptake vs. unbound oleate concentrations was best fitted by the Mic haelis-Menten equation (Vmax= 235+/-8.8 nmol.min(-1).g.liver(-1); Km=1 30+/-12 nM). As the albumin concentration was increased from 50 to 250 mu M, the unbound oleate clearance, calculated by either the undistri buted sinusoidal or venous equilibrium models, increased progressively , in violation of conventional pharmacokinetic theory, indicating an e nhancing effect of albumin on ligand uptake at low albumin concentrati ons. In contrast, there was no significant difference between measures of unbound clearance at albumin concentrations of 350 and 600 mu M. T o explain this phenomenon, the clearance data were examined for eviden ce of facilitation (accelerated dissociation of ligand:albumin complex es) by the clearance ratio test (''square root rule''). All deviations from the predictions of conventional theory were entirely attributabl e to pseudofacilitation. No data required explanation by a true facili tation model. (C) Journal of Hepatology.