Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wolfrum, C; Börchers, T; Sacchettini, JC; Spener, F.
Binding of fatty acids and peroxisome proliferators to orthologous fatty acid binding proteins from human, murine, and bovine liver.
Biochemistry. 2000; 39(6):1469-1474
Doi: 10.1021/bi991638u
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- Spener Friedrich
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- 5,8,11,14-Eicosatetraynoic Acid - metabolism
- Amino Acid Sequence -
- Animals -
- Bezafibrate - chemistry Bezafibrate - metabolism
- Calorimetry -
- Carrier Proteins - chemistry Carrier Proteins - metabolism
- Cattle -
- Fatty Acid-Binding Proteins -
- Fatty Acids - chemistry Fatty Acids - metabolism
- Humans -
- Ligands -
- Liver - metabolism
- Mice -
- Molecular Sequence Data -
- Myelin P2 Protein - chemistry Myelin P2 Protein - metabolism
- Neoplasm Proteins -
- Nerve Tissue Proteins -
- Peroxisome Proliferators - chemistry Peroxisome Proliferators - metabolism
- Protein Binding -
- Pyrimidines - chemistry Pyrimidines - metabolism
- Tumor Suppressor Proteins -