Lipid absorptions passing through the unstirred layers, brush-border membrane, and beyond

1993 ◽  
Vol 71 (8) ◽  
pp. 531-555 ◽  
Author(s):  
A. B. R. Thomson ◽  
C. Schoeller ◽  
M. Keelan ◽  
L. Smith ◽  
M. T. Clandinin
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Brush Border ◽  
Binding Proteins ◽  
Brush Border Membrane ◽  
Water Layer ◽  
Lipid Binding ◽  
Dietary Lipids ◽  
Unstirred Water Layer ◽  
Lipid Binding Proteins

Lipids are components of our diet and luminal secretions, with physicochemical characteristics that determine their digestion and absorption in the gastrointestinal tract. Lipids include triglycerides, phospholipids, and cholesterol. Dietary lipids contain approximately 97% triglycerides, with small amounts of phospholipids and cholesterol. These components are important in cell membrane composition, fluidity, peroxidation, prostaglandin and leukotriene synthesis, and cellular metabolic processes. Lipids are implicated in the mechanisms of brain development, inflammatory processes, atherosclerosis, carcinogenesis, aging, and cell renewal. Duodenal hydrolysis of dietary lipids and biliary phospholipids and cholesterol is carried out by pancreatic lipase, colipase, phospholipase A2, and cholesterol esterase. Bile acid solubilization results in mixed micelles and liposomes, in gel and liquid crystal phases. Lipid digestion products pass across the intestinal unstirred water layer. For long-chain fatty acids and cholesterol, passage across the unstirred water layer is rate limiting, whereas passage of short- and medium-chain fatty acids is limited by the brush-border membrane. Within the unstirred water layer, an acidic microclimate aids micellar dissociation so that protonated, and to a lesser extent, nonprotonated monomers then pass across the intestinal brush-border membrane. Absorptive mechanisms have been studied extensively in relation to lipid composition, fatty acid chain length, degree of unsaturation, essential fatty acid content, phospholipid components, and cholesterol. Enterocytes may take up lipids from the intestinal lumen or from lipoproteins of the bloodstream, but these pools are likely to be functionally distinct. Recent advances are reviewed, including recent advances in the area of microclimates, compartmentation, lipid binding proteins, intracellular trafficking, intestinal lipoproteins, release of lipids across the basolateral membrane, and dietary effects.Key words: diet effects, lipid binding proteins, lipoproteins.

scholarly journals Molecular mechanisms of long-chain fatty acids absorption

2018 ◽  
Vol 9 (3) ◽  
pp. 29-36
Author(s):  
A. Kh. Kade ◽  
A. I. Trofimenko ◽  
P. P. Polyakov ◽  
L. R. Gusaruk ◽  
O. P. Ishevskaia ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Brush Border Membrane ◽  
Web Of Science ◽  
Lipid Binding ◽  
Long Chain Fatty Acids ◽  
Lipid Binding Proteins ◽  
Long Chain ◽  
Chain Fatty Acids

The article presents about the role of several lipid-binding proteins expressed by the small intestine brush border membrane in the main steps of intestinal absorption of long-chain fatty acids and about changes in lipid profile caused by failed absorbtion. The system literature search is performed on Scopus databases, Web of Science, MedLine.

Intracellular fatty acid trafficking and the role of cytosolic lipid binding proteins

1989 ◽  
Vol 28 (4) ◽  
pp. 245-272 ◽  
Author(s):  
Valerie Matarese ◽  
Randy L. Stone ◽  
David W. Waggoner ◽  
David A. Bernlohr
Keyword(s):  
Fatty Acid ◽  
Binding Proteins ◽  
Lipid Binding ◽  
Lipid Binding Proteins

scholarly journals Ligand Entry into Fatty Acid Binding Protein via Local Unfolding instead of Gap Widening

2019 ◽  
Author(s):  
T Xiao ◽  
Y Lu ◽  
J Fan ◽  
D Yang
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Proteins ◽  
Lipid Binding ◽  
Relaxation Dispersion ◽  
Chemical Exchange Saturation Transfer ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Protein Cavity ◽  
Local Unfolding

AbstractFatty acid binding proteins (FABPs) play an important role in transportation of fatty acids. Despite intensive studies, how fatty acids enter the protein cavity for binding is still controversial. Here, a gap-closed variant of human intestinal FABP was generated by mutagenesis, in which the gap is locked by a disulfide bridge. According to its structure determined here by NMR, this variant has no obvious openings as the ligand entrance and the gap cannot be widened by internal dynamics. Nevertheless, it still uptakes fatty acids and other ligands. NMR relaxation dispersion, chemical exchange saturation transfer and hydrogen-deuterium exchange experiments show that the variant exists in a major native state, two minor native-like state, and two locally unfolded states in aqueous solution. Local unfolding of either βB–βD or helix 2 can generate an opening large enough for ligands to enter the protein cavity, but only the fast local unfolding of helix 2 is relevant to the ligand entry process.Statement of SignificanceFatty acid binding proteins transport fatty acids to specific organelles in the cell. To enable the transport, fatty acids must enter and leave the protein cavity. In spite of many studies, how fatty acids enter the protein cavity remains controversial. Using mutagenesis and biophysical techniques, we have resolved the disagreement and further showed that local unfolding of the second helix can generate a transient opening to allow ligands to enter the protein cavity. Since lipid binding proteins are highly conserved in 3D structures and ligand binding, all of them may use the same local unfolding mechanism for ligand uptake and release.

scholarly journals Functional analysis of peroxisome-proliferator-responsive element motifs in genes of fatty acid-binding proteins

2004 ◽  
Vol 382 (1) ◽  
pp. 239-245 ◽  
Author(s):  
Christian SCHACHTRUP ◽  
Tanja EMMLER ◽  
Bertram BLECK ◽  
Anton SANDQVIST ◽  
Friedrich SPENER
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Proteins ◽  
Lipid Binding ◽  
Fatty Acid Binding Proteins ◽  
Computer Search ◽  
Peroxisome Proliferator ◽  
Fatty Acid Binding ◽  
Responsive Element

Retinoic acids and long-chain fatty acids are lipophilic agonists of nuclear receptors such as RXRs (retinoic X receptors) and PPARs (peroxisome-proliferator-activated receptors) respectively. These agonists are also ligands of intracellular lipid-binding proteins, which include FABPs (fatty acid-binding proteins). We reported previously that L (liver-type)-FABP targets fatty acids to the nucleus of hepatocytes and affects PPARα activation, which binds together with an RXR subtype to a PPRE (peroxisome-proliferator-responsive element). In the present study, we first determined the optimal combination of murine PPAR/RXR subtypes for binding to known murine FABP-PPREs and to those found by computer search and then tested their in vitro functionality. We show that all PPARs bind to L-FABP-PPRE, PPARα, PPARγ1 and PPARγ2 to A (adipocyte-type)-FABP-PPRE. All PPAR/RXR heterodimers transactivate L-FABP-PPRE, best are combinations of PPARα with RXRα or RXRγ. In contrast, PPARα heterodimers do not transactivate A-FABP-PPRE, best combinations are of PPARγ1 with RXRα and RXRγ, and of PPARγ2 with all RXR subtypes. We found that the predicted E (epidermal-type)- and H (heart-type)-FABP-PPREs are not activated by any PPAR/RXR combination without or with the PPAR pan-agonist bezafibrate. In the same way, C2C12 myoblasts transfected with promoter fragments of E-FABP and H-FABP genes containing putative PPREs are also not activated through stimulation of PPARs with bezafibrate applied to the cells. These results demonstrate that only PPREs of L- and A-FABP promoters are functional, and that binding of PPAR/RXR heterodimers to a PPRE in vitro does not necessarily predict transactivation.

Intestinal transport of bile acids

1981 ◽  
Vol 241 (2) ◽  
pp. G83-G92 ◽  
Author(s):  
F. A. Wilson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Active Transport ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Water Layer ◽  
Unstirred Layer ◽  
Jejunal Mucosa ◽  
Acid Uptake ◽  
Unstirred Water Layer

The intestinal absorption of bile acids is determined by two resistances: diffusion through an unstirred water layer and penetration of the cell membrane. Passive jejunal uptake of polar bile acids is limited by the mucosal membrane, whereas the unstirred layer exerts resistance on uptake of more nonpolar species. After correction for the diffusion layer, the membrane permeability coefficients were derived to calculate the delta delta Fw leads to 1 associated with uptake of the -OH (+874 cal.mol-1), glycine (+897), and taurine (+1,498) groups. The delta delta F1 (-6,126 cal.mol-1) for the -OH group suggested that the jejunal mucosa is a relatively polar membrane. The unstirred layer is even more rate limiting for bile acid uptake from micellar solutions. Once the micelle reaches the aqueous-membrane interface, it is not absorbed intact, but rather uptake is explained in terms of monomers in the aqueous phase that are in equilibrium with the micelle. The presence of the unstirred water layer introduces artifactually high Km values for active transport. Structure-activity studies suggest that the ileal recognition site consists of a component for the steroid moiety, a positive charge, and an adjacent anionic charge. The energy for active transport arises from the Na+ gradient across the brush-border membrane that, in turn, is dependent on the activity of Na+-K+-ATPase. The Na+ stimulation of bile acid transport across the ileal brush-border membrane is due to influx coupling via a cotransport system rather than electrical coupling to satisfy overall electrical neutrality.

Fatty acids in cell signalling: Modulation by lipid binding proteins

1995 ◽  
Vol 52 (2-3) ◽  
pp. 121-127 ◽  
Author(s):  
J.F.C. Glatz ◽  
T. Börchers ◽  
F. Spener ◽  
Ger J. van der Vusse
Keyword(s):  
Fatty Acids ◽  
Binding Proteins ◽  
Cell Signalling ◽  
Lipid Binding ◽  
Lipid Binding Proteins
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