Membrane binding proteins are the major determinants for the hepatocellular transmembrane flux of long-chain fatty acids bound to albumin

Rajaraman, G., Roberts, M. S., Hung, D., Wang, G. Q. and Burczynski, F. J. (2005) Membrane binding proteins are the major determinants for the hepatocellular transmembrane flux of long-chain fatty acids bound to albumin. Pharmaceutical Research, 22 11: 1793-1804. doi:10.1007/s11095-005-7248-2


Author Rajaraman, G.
Roberts, M. S.
Hung, D.
Wang, G. Q.
Burczynski, F. J.
Title Membrane binding proteins are the major determinants for the hepatocellular transmembrane flux of long-chain fatty acids bound to albumin
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
Publication date 2005
Sub-type Article (original research)
DOI 10.1007/s11095-005-7248-2
Volume 22
Issue 11
Start page 1793
End page 1804
Total pages 12
Editor V. H. L. Lee
Place of publication USA
Publisher Plenum US
Collection year 2005
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730199 Clinical health not specific to particular organs, diseases and conditions
Formatted abstract
Purpose The hepatic transmembrane flux of long-chain fatty acids (LCFA) occurs through passive and fatty acid transport protein facilitated processes from blood. The extent that these transport processes can be related to the unbound and protein-bound fractions of LCFA in blood is not clear.
Methods We used hepatocyte suspensions, hepatoma monolayers, and perfused rat livers to quantitate the transport of purified [3H]palmitate ([3H]PA) and 12-(N-methyl)-N-[(7-nitrobenz-2oxa-1,3-diazol-4yl-)amino]octadecanoicacid (12-NBDS) from solutions with a constant unbound LCFA concentration with varying bovine serum albumin (BSA) concentrations and in the presence and absence of antisera raised against cytosolic liver fatty acid binding protein (L-FABP).
Results In the absence of L-FABP antisera, using an unbound ligand concentration that was adjusted to remain constant at each BSA concentration, hepatocyte [3H]PA and 12-NBDS uptake rates increased linearly with an increase in BSA concentration (p < 0.0001). In the presence of L-FABP antisera, [3H]PA uptake showed a greater reduction in the presence of 100 μM BSA than 5 μM BSA. The calculated permeability surface area product (PS) confirmed that both unbound and bound fractions of LCFA contributed to the overall flux, but only the PS for the protein-bound fraction was reduced in the presence of L-FABP antisera. In situ rat liver perfusion studies showed that the only rate process for the disposition of [3H]PA in the liver inhibited by L-FABP antisera was that for influx, as defined by PS, and that it reduced PS in the perfused liver by 42%.
Conclusion These results suggest that, at physiological albumin concentrations, most of the LCFA uptake is mediated from that bound to albumin by a hepatocyte basolateral membrane transport protein, and uptake of unbound LCFA occurring by passive diffusion contributes a minor component.

Keyword Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Albumin
Fabp
Hepatocyte
Liver
Long-chain Fatty Acid
Palmitate
Stearate
Uptake
Rat-liver
Palmitate Uptake
Hepatocyte Suspensions
Facilitated Uptake
Hepatic Transport
Cellular Uptake
Surface-charge
Serum-albumin
Oleate
Cells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2006 Higher Education Research Data Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 05:38:54 EST