We measured uptake of a representative free fatty acid, oleate, by the single-pass perfused rat liver at oleate:albumin
molar ratios of 0.01 to 2 : 1. For each ratio, uptake was studied at albumin concentrations from 50 to 600 ItM. When
uptake velocity was plotted as a function of the albumin concentration, the data at each ratio exhibited a pseudosaturation
pattern as previously observed in isolated cells (J Clin Invest 84: 1325). At a physiologic albumin concentration of 600
IzM, a plot of uptake vs. unbound oleate concentrations was best fitted by the Michaelis-Menten equation (Vmax=
235_+8.8 nmol. min-~ .g • liver-~: Kin= 130+_-12 nM). As the albumin concentration was increased from 50 to 250 ltM,
the unbound oleate clearance, calculated by either the undistributed sinusoidal or venous equilibrium models, increased
progressively, in violation of conventional pharmacokinetic theory, indicating an enhancing effect of albumin on ligand
uptake at low albumin concentrations. In contrast, there was no significant difference between measures of unbound
clearance at albumin concentrations of 350 and 600 I~M. To explain this phenomenon, the clearance data were examined
for evidence of facilitation (accelerated dissociation of ligand : albumin complexes) by the clearance ratio test ("square
root rule"). All deviations from the predictions of conventional theory were entirely attributable to pseudofacilitation. No
data required explanation by a true facilitation model.
