Hepatocyte [3H]-palmitate uptake: effect of albumin surface charge modification

Can J Physiol Pharmacol. 2001 Oct;79(10):868-75.

Abstract

The role of plasma proteins on the cellular uptake of lipophilic substrates has perplexed investigators for many years. We tested the hypothesis that an ionic interaction between the protein-ligand complex and hepatocyte surface may be responsible for supplying more ligand to the cell for uptake. The surface-charged groups on albumin were modified to yield proteins having a range of isoelectric points (ALB, ALBs, ALBm, ALBe had values of 4.8-5.0, 4.5-4.7, 3.0-3.5, 8.4-8.6, respectively). [3H]-Palmitate uptake studies were performed with adult rat hepatocyte suspensions using similar unbound ligand fractions in the presence of the different binding proteins. Mass spectrometry, isoelectric focusing (pI), and heptane:water partitioning were used to determine protein molecular weight, pI, and protein-palmitate equilibrium binding constant, respectively. Hepatocyte [3H]-palmitate clearance in the presence of ALBs and ALBm were significantly lower (p < 0.05) than ALB, whereas [3H]-palmitate clearance in the presence of ALBe was significantly higher (p < 0.05) than ALB. The data were consistent with the notion that ionic interactions between extracellular protein-ligand complexes and the hepatocyte surface facilitate the uptake of long-chain fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism*
  • Algorithms
  • Animals
  • Cations
  • Fatty Acids / metabolism
  • Female
  • In Vitro Techniques
  • Isoelectric Focusing
  • Kinetics
  • Liver / metabolism*
  • Maleates / chemical synthesis
  • Maleates / metabolism
  • Molecular Weight
  • Palmitates / metabolism*
  • Protein Conformation
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Electrospray Ionization
  • Succinates / chemical synthesis
  • Succinates / metabolism
  • Surface Properties

Substances

  • Albumins
  • Cations
  • Fatty Acids
  • Maleates
  • Palmitates
  • Succinates