Specific high affinity binding of lipoxygenase metabolites of arachidonic acid by liver fatty acid binding protein

Haider Raza, Jagan R. Pongubala, Sam Sorof

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

Liver fatty acid binding protein (L-FABP) binds avidly the arachidonic acid metabolites, hydroperoxyeicosatetraenoic acids (HPETEs) and hydroxyeicosatetraenoic acids (HETEs). Binding of 15-[3H] HPETE was specific, saturable, reversible, and rapid. Protein specificity was indicated by the following order: L-FABP>bovine serum albumin>ovalbumin = β-lactoglobulin>ribonuclease. Ligand specificity was evidenced by the following order of apparent competition: 15-HPETE ≥ 5-HETE ≥ 5-HPETE = oleic acid>12-HETE>12-HPETE ≥ 15-HETE>prostaglandin E1 ≫ leukotriene C4>prostaglandin E2 ≫ thromboxane B2 = leukotriene B4. Once bound, 15-HPETE was reversibly displaced. Ligand was recovered from the protein complex and confirmed to be 15-[3H]HPETE by TLC. L-FABP bound HPETE with a dissociation constant of 76 nM,5-HETE at 175 nM, and 15-HETE at 1.8 μM, and the reference fatty acids oleic acid at 1.2 μM and arachidonic acid at 1.7 μM. Thus, the affinity was approximately 16-fold greater for 15-HPETE, and 7-fold higher for 5-HETE, than for oleic acid. The need exists for studies of complexes of L-FABP with the HPETEs and HETEs in hepatocytes, especially since L-FABP has previously been associated with mitosis in normal hepatocytes, and shown to be the target protein of two liver carcinogens, and these arachidonic acid metabolites have been found to be able to modulate activities related to cell growth.

Original languageEnglish
Pages (from-to)448-455
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume161
Issue number2
DOIs
Publication statusPublished - Jun 15 1989
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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