Binding of fatty acids and peroxisome proliferators to orthologous fatty acid binding proteins from human, murine, and bovine liver. | Academic Article individual record
abstract

Liver-type fatty acid binding protein (L-FABP) has been proposed to be involved in the transport of fatty acids and peroxisome proliferators from the cytosol into the nucleus for interaction with the peroxisome proliferator-activated receptors (PPARs). On the basis of this premise, we investigated by isothermal titration calorimetry the binding of myristic, stearic, oleic, and docosahexaenoic acids to three orthologous L-FABPs and compared these results to those obtained for several xenobiotics [Wy14,643, bezafibrate, 5,8,11,14-eicosatetraynoic acid (ETYA), and BRL48,482] known for their peroxisome proliferating activity in rodents. Recombinant human, murine, and bovine L-FABPs were analyzed and the thermodynamic data were obtained. Our studies showed that fatty acids bound with a stoichiometry of 2:1, fatty acid to protein, with dissociation constants for the first binding site in the nanomolar range. With dissociation constants above 1 microM the drug peroxisome proliferators showed weaker binding, with the exception of arachidonate analogue ETYA, which bound with a similar affinity as the natural fatty acid. Some of the thermodynamic data obtained for fatty acid binding could be explained by differences in protein structure. Moreover, our results revealed that binding affinities were not determined by ligand solubility in the aqueous phase.

author list (cited authors)
Wolfrum, C., Börchers, T., Sacchettini, J. C., & Spener, F.
publication date
2000
published in
BIOCHEMISTRY Journal
keywords
  • Mice
  • Nerve Tissue Proteins
  • Liver
  • Fatty Acid-binding Proteins
  • Animals
  • 5,8,11,14-eicosatetraynoic Acid
  • Amino Acid Sequence
  • Molecular Sequence Data
  • Protein Binding
  • Peroxisome Proliferators
  • Humans
  • Fatty Acid-binding Protein 7
  • Ligands
  • Neoplasm Proteins
  • Calorimetry
  • Bezafibrate
  • Myelin P2 Protein
  • Fatty Acids
  • Tumor Suppressor Proteins
  • Carrier Proteins
  • Pyrimidines
  • Cattle
altmetric score

3.0

citation count

51