Disease relevance of Fabp2

• In situ hybridization of rat ileal tissue also revealed differing patterns of mRNA expression for liver fatty acid-binding protein (L-FABP) and I-FABP [1].
• To undertake such a study we expressed the coding region of a full length I-FABP cDNA in Escherichia coli and purified large quantities of the protein [2].
• I-FABP is released into the peripheral circulation after reversible intestinal ischemic injury and has potential as a biochemical marker to facilitate the early detection of mesenteric ischemia [3].
• A prokaryotic expression vector containing the rec A promoter and a translational enhancer element from the gene 10 leader of bacteriophage T7 was used to direct efficient synthesis of rat intestinal fatty acid binding protein (I-FABP) in E. coli [4].

High impact information on Fabp2

• Collectively, these results indicate that the alpha-helical region of IFABP is involved in membrane interactions and thus plays a critical role in the collisional mechanism of fatty acid transfer from IFABP to phospholipid membranes [5].
• Rat intestinal fatty acid binding protein (I-FABP) is a member of a family of cytoplasmic hydrophobic ligand-binding proteins [6].
• To gain insights about the contribution of bound fatty acid to I-FABP's conformation and mechanism of ligand binding, we have determined the structure of Escherichia coli-derived rat apo-I-FABP to 1.96-A resolution and compared it to the recently refined structure of I-FABP with bound palmitate [6].
• A series of point mutants in rat IFABP was engineered in which the lysine positive charges in this domain were eliminated or reversed [7].
• These data suggest that the binding of non-fatty acid lipophilic drugs to I-FABP may increase the cytosolic solubility of these compounds and thereby facilitate drug transport from the intestinal lumen across the enterocyte to sites of distribution and metabolism [8].

Chemical compound and disease context of Fabp2

• The sterol binding specificity of rat recombinant liver fatty acid binding protein (L-FABP) and intestinal fatty acid binding protein (I-FABP) was characterized with [3H]cholesterol and a fluorescent sterol analog dehydroergosterol [9].

Biological context of Fabp2

• Intestinal fatty acid binding protein (IFABP) is thought to participate in the intracellular transport of fatty acids (FAs) [10].
• IFABP is a small beta-barrel protein with a short helix-turn-helix motif near the N-terminus that is thought to participate in the regulation of the uptake and delivery of fatty acids [11].
• Forster energy transfer from I-FABP tryptophan to bound cis-parinaric acid resulted in quenching of tryptophan lifetime and appearance of sensitized lifetime of bound cis-parinaric acid [12].
• The variation of these Kd values with FA molecular species is highly correlated with the solubility of the FA in water, suggesting that all these FA bind with a similar conformation in the I-FABP binding site [13].
• Here we report on an intestinal cell culture system expressing I-FABP during cell differentiation and the modulation of expression by extracellular factors [14].

Anatomical context of Fabp2

• These studies demonstrate that physiological concentrations of PYY can regulate I-FABP and place this peptide in a key position as part of a feedback system that determines the processing of cytosolic FFA in the enterocyte [1].
• The sustained expression of I-FABP transcripts in the villar tips suggests (unlike L-FABP) that older terminally differentiated cell populations of the mucosa can still be PYY responsive [1].
• Fatty acid transfer from IFABP to phospholipid membranes is proposed to occur during protein-membrane collisional interactions [10].
• Rat liver fatty acid binding protein (L-FABP) and rat intestine fatty acid binding protein (I-FABP) are homologous proteins which are both found in intestinal epithelial cells [15].
• BACKGROUND: Lipid-binding proteins have been identified in the enterocyte, including the cytosolic intestinal and liver fatty acid binding proteins (I-FABP and L-FABP, respectively) as well as the brush border membrane fatty acid transporter (FAT) [16].

Associations of Fabp2 with chemical compounds

• This localization correlated with the expression pattern of I-FABP mRNA in the hBRIE 380i cells where changes in transcripts were observed only in differentiated cells that did not incorporate bromodeoxyuridine [1].
• The crystal structure of Escherichia coli-derived rat I-FABP with a single molecule of bound palmitate has been refined to 2 A resolution using a combination of least-squares methods, energy refinement and molecular dynamics [17].
• In the present work, we studied in detail the interaction of each compound with IFABP as a function of temperature and in the absence or in the presence of oleic acid [11].
• By contrast, we were not able to detect a significant difference in the affinity of I-FABP for palmitate, oleate, and arachidonate [2].
• Fatty acid binding also blocked the accessibility of L-FABP tyrosine and I-FABP tryptophan to Stern-Volmer quenching by acrylamide, indicating that these amino acids were present in the fatty acid-binding pocket [12].

Physical interactions of Fabp2

• Binding and proximity relationships of fatty acids with recombinant rat liver fatty acid-binding protein (L-FABP) and intestinal fatty acid-binding protein (I-FABP) were studied with absorption and fluorescence spectroscopy [12].
• We constructed 18 single amino acid mutants of the adipocyte fatty acid-binding protein (A-FABP) and 17 of the intestinal fatty acid-binding protein (I-FABP), at locations in the fatty acid (FA) binding sites [18].
• Cellular retinol-binding protein II (CRBP-II) and intestinal fatty acid-binding protein (I-FABP) are both expressed in small intestinal enterocytes and exhibit 31% sequence identity [19].

Regulatory relationships of Fabp2

• The data show that I-FABP expression is limited to a differentiated population of hBRIE 380i cells and that the expression can be regulated by factors present in the extracellular matrix as well as involved in regulation of replication or metabolic state of the cell [14].

Other interactions of Fabp2

• Intestinal fatty acid binding protein (IFABP) and liver FABP (LFABP), homologous proteins expressed at high levels in intestinal absorptive cells, employ markedly different mechanisms for the transfer of fatty acids (FAs) to acceptor membranes [20].
• H-FABP immunoreactivity was first detected at embryonic day 20 (E20), with predominant localization in the parietal cells, whereas I-FABP immunoreactivity was detected at the day of birth in the surface mucous cells [21].
• These studies have isolated a 14 kDa bile acid-binding protein from rat ileal cytosol which is immunologically and biochemically distinct from I-FABP and L-FABP [22].
• X-ray diffraction data suggest that the unit cell parameters of crystalline apo-CRBP II resemble those of I-FABP [23].
• Finally, the A-FABP proteins, in contrast to the I-FABP proteins, reveal significant heat capacity changes (DeltaCp) upon FA binding, and substitutions at residues Arg106 and Arg126 reduce the magnitude of DeltaCp [18].

Analytical, diagnostic and therapeutic context of Fabp2

• Three independent lines of evidence, namely, fluorescence spectroscopy, circular dichroism, and limited proteolysis, indicate that there is an equilibrium among different conformations of IFABP, which differ in the extent of flexibility of the helical domain [11].
• These results are consistent with a close proximity of bound fatty acids to the tyrosine and tryptophan residues and with immobilization of the polyene fatty acids in the fatty acid-binding site(s) of L-FABP and I-FABP [12].
• We have previously described the crystallization of a homologous rat intestinal fatty acid-binding protein (I-FABP) isolated from Escherichia coli containing a suitably constructed prokaryotic expression vector (Sacchettini, J. C., Meininger, T. A., Lowe, J. B., Gordon, J. I., and Banaszak, L. J., J. Biol. Chem. 262, 5428-5430) [23].
• Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward [24].
• OBJECTIVE: To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes [24].

References