Fatty add-binding protein

Liver fatty add-binding protein LFABP 2.7 Scapin et al. (1990)... 

Cystatin C L-type fatty add-binding protein (L-FABP)... 

Figure 7.8 Comparison of oxygen transport from lung to a cell and then into a mitochondrion with fatty acid transport from an adipocyte to a cell and then into the mitochondria in various tissues/ organs. Fatty add is transported in blood bound to albumin, oxygen is transported in blood bound to haemoglobin. Fatly add is transported within the cell attached to the fatty acid-binding protein (BP), oxygen is transported within a cell attached to myoglobin (Mb). Alb represents albumin, Hb haemoglobin.

Sacchettini JC, Gordon JI (1993) Rat intestinal fatty acid binding protein. A model system for analyzing the forces that can bind fatty adds to proteins. J Biol Chem 268 18399 102 Safo PK, Regehr WG (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 48 647-59... 

The following brief overview describes the modes of transport of FFAs in the body and serves as a preview to the description of the mitochondrial transport system. FFAs arc generated by lipolysis of TGs stored in lipocytes of adipose tissue (adipocytes) and in lipocytes of other organs. Fatty adds are also released by the action of lipoprotein lipase in the bloodstream. Special membrane-bound proteins mediate the transfer of FFAs across the membranes of various cells, such as entenocytes and hepatocytes, Wthin the cell, FFAs are carried on special proteins called fatty acid-binding proteins. These proteins have low molecular weights, about 15,000, and can account for 5% of cytosolic protein (Bemlohr ef al., 199. ... 

Samuel BS, Shaito A, Motoike T, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-add binding G protein-coupled receptor, Gpr41. Proc Natl Acad Set USA. 2008 105(43) 16767—16772. 

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

Reduced storage of bilirubin can be caused by the bilirubin competing with exogenous substances for binding to the Y protein or with long-chain fatty adds for binding to the Z protdn. Thus bilirubin may diffuse back from the hver cell into the blood. 

Data presented in previous sections revealed that the concentration of FFAs in plasma may reach 2.0 mM during exercise. How is this possible when the highest attainable concentration in water is only about 0,1 mM This problem was resolved by nature by use of albumin as a vehicle for the transport of FFAs within the circulation. Albumin constitutes about 60% of the protein of blood plasma. It is a major carrier of FFAs, other metabolites, hormones, and drugs- Serum albumin has the capadty to carry several fatty adds. Figure 4.45 shows results from an experiment usingpurificdalbumin.Thenumberoffattyacid molecules bound per protein molecule is plotted versus the concentration of unbound fatty acids in solution. The study, conducted with lauric acid (12 carbons) and myristic add (14 carbons), demonstrates that one protein molecule is able to bind at least 8 or 9 molecules of fatty acid. Albumin has a molecular weight of 69 kDa and occurs in human plasma at a concentration of about 0.6 mM (40 mg/ml) (Halliwell, 1988). 

Polymyxins are antibiotics produced by the bacterium Bacillus polymyxa. They are protein derivatives having one end that is hydrophobic because of an attached fatty add. The opposite end is hydrophilic. Because of these properties, the polymyxins bind to membranes with the hydrophobic end embedded within the membrane, while the hydrophihc end remains outside the cell. As a result, the integrity of the membrane is disrupted, and leakage of cellular constituents occurs, causing cell death. 

Abbreviations a-BFAs anteiso-branched fatty acids AGP acyl carrier protein BHLH active soluble domain of SREBP CNS central nervous system DSD delta 5 desaturase D6D delta 6 desaturase ER endoplasmic reticulum Hik histidine kinase HUFA highly unsaturated fatty acid LXR liver X receptor MUFA monounsaturated fatty add NF-Y nuclear factor Y PLs phospholipids PP peroxisome proliferator PPAR PP-activated receptor PPRE PP response element PUFA polyunsaturated fatty acid PUFA-BP PUFA binding protein PUFA-RE PUFA response element RXR retinoid X receptor SCAP SREBP cleavage-activating protein SCD steraroyl CoA desaturase SFA saturated fatty acid SRE sterol response... 

After oxygenation, the fate of fatty add epoxides is diverse and varied (Fig. 13.4). EETs may transactivate membrane receptors or directly bind to ion charmels or other proteins to cause biological effects. All four EET regioisomers can be esterified into phospholipids in cell mem-... 

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