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EnglishWe 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.
| Titolo: | Oleate uptake kinetics in the perfused rat liver are consistent with pseudofacilitation by albumin | |
| Autori: | ||
| Data di pubblicazione: | 1994 | |
| Rivista: | ||
| Abstract: | 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. | |
| Handle: | http://hdl.handle.net/11390/1092755 | |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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| Oleate uptake kinetics in the perfused rat liver JHepatol.pdf | Versione Editoriale (PDF) | Non pubblico | Accesso ristretto Richiedi una copia |
http://hdl.handle.net/11390/1092755
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