Purification and characterization of fatty acid-binding protein from human placenta.
TL;DR: Ouchterlony double immunodiffusion studies have confirmed the immunochemical identity of these three fractions of placental FABP, which revealed that DE-II binds long chain saturated and unsaturated fatty acids nonspecifically, whereas DE-III is mainly an arachidonic acid carrier.
Abstract: Purification of a cytosolic fatty acid-binding protein (FABP) from developing human placenta has been achieved, and its role in modulating the inhibition of human placental glucose-6-phosphate dehydrogenase (G6PD) by palmitoyl-CoA (PAL-CoA) has been studied. FABP was resolved into three peaks, viz. DE-I, DE-II and DE-III, by DEAE cellulose chromatography. DE-I was almost lipid-free. Presence of endogenous fatty acids in DE-II and DE-III was detected by thin layer chromatography (TLC). Fatty acids were the only detectable lipid component in these fractions. Gas liquid chromatography (GLC) analysis revealed that DE-II binds long chain saturated and unsaturated fatty acids nonspecifically, whereas DE-III is mainly an arachidonic acid carrier. Each of these fractions, viz. DE-I, DE-II and DE-III, has a molecular weight of 14,200 Daltons. Ouchterlony double immunodiffusion studies have confirmed the immunochemical identity of these three fractions of placental FABP. Separation in ion exchanger may be due to their different isoelectric points and varied types of binding affinities. Human placental G6PD was inhibited 50% by 0.03 mM PAL-CoA. The DE-II fraction of FABP enhanced the activity of G6PD in the absence of added PAL-CoA and protected against PAL-CoA inhibition of the enzyme. Such a modulating effect of FABP in this inhibition is attributable to binding of long chain acyl-CoA rather than to a direct effect of FABP on the enzyme itself.
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TL;DR: Article de synthese sur les donnees recentes de caracteristiques structurales et physicochimiques de divers types of proteines de liaison aux acides gras, avec la signification physiologique de ces diversites.
366 citations
TL;DR: A considerable body of indirect evidence is provided supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids and the existence of structure- and tissue-specific specialization of function among different members of the F ABP gene family.
Abstract: Cytosolic fatty acid binding proteins (FABP) belong to a gene family of which eight members have been conclusively identified. These 14–15 kDa proteins are abundantly expressed in a highly tissue-specific manner. Although the functions of the cytosolic FABP are not clearly established, they appear to enhance the transfer of long-chain fatty acids between artificial and native lipid membranes, and also to have a stimulatory effect on a number of enzymes of fatty acid metabolism in vitro. These findings, as well as the tissue expression, ligand binding properties, ontogeny and regulation of these proteins provide a considerable body of indirect evidence supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids. The available data also support the existence of structure- and tissue-specific specialization of function among different members of the FABP gene family. Moreover, FABP may also have a possible role in the modulation of cell growth and proliferation, possibly by virtue of their affinity for ligands such as prostaglandins, leukotrienes and fatty acids, which are known to influence cell growth activity. FABP structurally unrelated to the cytosolic gene family have also been identified in the plasma membranes of several tissues (FABPpm). These proteins have not been fully characterized to date, but strong evidence suggests that they function in the transport of long-chain fatty acids across the plasma membrane.
167 citations
TL;DR: The strengths and weaknesses of H-FABP as a clinically applicable marker of myocyte necrosis in the context of acute coronary syndromes are reviewed.
Abstract: Heart fatty-acid-binding protein (FABP) is a small cytosolic protein that is abundant in the heart and has low concentrations in the blood and in tissues outside the heart. It appears in the blood as early as 1.5 h after onset of symptoms of infarction, peaks around 6 h and returns to baseline values in 24 h. These features of H-FABP make it an excellent potential candidate for the detection of acute myocardial infarction (AMI). We review the strengths and weaknesses of H-FABP as a clinically applicable marker of myocyte necrosis in the context of acute coronary syndromes.
147 citations
TL;DR: Which FABPs form biochemically defined or true isoforms versus FABP that form additional forms, operationally defined as isoforms, is critically evaluated.
127 citations
TL;DR: The identity, nature, function, and pathobiology of these fascinating newly discovered long-chain fatty acyl-CoA binding proteins are explored.
Abstract: The physiological role of long-chain fatty acyl-CoA is thought to be primarily in intermediary metabolism of fatty acids. However, recent data show that nM to μM levels of these lipophilic molecules are potent regulators of cell functionsin vitro. Although long-chain fatty acyl-CoA are present at several hundred μM concentration in the cell, very little long-chain fatty acyl-CoA actually exists as free or unbound molecules, but rather is bound with high affinity to membrane lipids and/or proteins. Recently, there is growing awareness that cytosol contains nonenzymatic proteins also capable of binding long-chain fatty acyl-CoA with high affinity. Although the identity of the cytosolic long-chain fatty acyl-CoA binding protein(s) has been the subject of some controversy, there is growing evidence that several diverse nonenzymatic cytosolic proteins will bind long-chain fatty acyl-CoA. Not only does acyl-CoA binding protein specifically bind medium and long-chain fatty acyl-CoA (LCFA-CoA), but ubiquitous proteins with multiple ligand specificities such as the fatty acid binding proteins and sterol carrier protein-2 also bind LCFA-CoA with high affinity. The potential of these acyl-CoA binding proteins to influence the level of free LCFA-CoA and thereby the amount of LCFA-CoA bound to regulatory sites in proteins and enzymes is only now being examined in detail. The purpose of this article is to explore the identity, nature, function, and pathobiology of these fascinating newly discovered long-chain fatty acyl-CoA binding proteins. The relative contributions of these three different protein families to LCFA-CoA utilization and/or regulation of cellular activities are the focus of new directions in this field.
126 citations
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TL;DR: Two hepatic cytoplasmic protein fractions, designated Y and Z, which bind sulfobromophthalein (BSP), bilirubin, and other organic anions, have been separated by G75 Sephadex gel filtration and appear to be important in the transfer of Organic anions from plasma into the liver.
Abstract: Two hepatic cytoplasmic protein fractions, designated Y and Z, which bind sulfobromophthalein (BSP), bilirubin, and other organic anions, have been separated by G75 Sephadex gel filtration. The physiologic role of these protein fractions has been investigated. They are present in the 110,000 g supernatant fraction from the livers of all the species tested (rats, mice, guinea pigs, Rhesus monkeys, sheep, and man). Tissues which do not preferentially extract BSP or bilirubin from plasma do not contain these fractions, with the exception of small intestinal mucosa which contains Z. Anion binding by Y and Z fractions is not due to contamination with albumin. These fractions are responsible for the cytoplasmic localization of bilirubin in Gunn rats, and the fractions bind bilirubin, BSP, or indocyanine green (ICG), whether given in vivo or added in vitro to liver supernate from normal rats. Flavaspidic acid-N-methylglucaminate, bunamiodyl, and iodipamide, drugs known to interfere with the hepatic uptake mechanism, compete with bilirubin and BSP for binding to Z. These proteins appear to be important in the transfer of organic anions from plasma into the liver and provide a tool for the investigation of hepatic uptake mechanisms.
537 citations
297 citations
TL;DR: The abundance of FABP, its importance in the cytosolic binding of endogenous as well as exogenous fatty acids, and its demonstrated correlation with rates of hepatocyte fatty acid utilization provide additional evidence for its relationship to the cellular metabolism of long chain fatty acids.
265 citations
TL;DR: Observations support the concept that the major role of these proteins is to facilitate the entry of lipids into cells and/or their subsequent intracellular transport and compartmentalization.
175 citations
TL;DR: The citrate-condensing enzyme (citrate oxaloacetate-lyase (CoA-acetylating), EC 4.1.3.7) can be partially protected from palmityl-CoA inhibition by oxalo acetate, and it is suggested that the interaction is not physiologically significant.
129 citations