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Query: UMLS:C0027960 (mole)
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A review of the available information about fatty acid binding to plasma albumin is presented. Albumin is composed of a single polypeptide chain, folded so as to form three or four spherical units. The strong fatty acid binding sites probably are located in crevices between these spherical regions. The anionic form of the fatty acid binds to albumin. Most of the binding energy comes from nonpolar interactions between the fatty acid hydrocarbon chain and uncharged amino acid side chains that line the binding sites. The binding sites are somewhat pliable, and their configuration can adapt to fit the incoming fatty acid. Stepwise association constants for binding to human albumin of fatty acids containing 6-18 carbon atoms are presented. These data indicate that each mole of fatty acid binds with a different affinity and that the association constants for multiple binding diminish sequentially, i.e., kappa 1 greater than kappa 2 greater than kappa 3 greater ... greater kappan. Because of uncertainties concerning fatty acid association in aqueous solutions, the constants for the 14-18 carbon acids probably are not definitive. In the usual physiological concentration range, free fatty acids do not displace appreciable amounts of a second organic compound from albumin. Sensitive spectrophotometric analyses revealed, however, that even small increases in free fatty acid concentration alter the molecular interaction between human albumin and another organic compound.
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PMID:Fatty acid binding to plasma albumin. 23 51

Albumin was isolated from pooled fetal serum obtained at normal delivery at term and from pooled adult plasma. Albumin isolation was carried out by means of PEG precipitation followed by ion exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (6 nM) to albumin (40 g/l) was measured by equilibrium dialysis at 37 degrees C. The unbound fraction (mean +/- SD) for fetal and adult albumin of diazepam was 1.86 +/- 0.24 and 1.82 +/- 0.15% (NS), that of digitoxin was 3.18 +/- 0.27 and 3.36 +/- 0.04% (NS) and that of salicylic acid was 11.65 +/- 0.99 and 9.47 +/- 0.75% (p less than 0.05), respectively. With both fetal and adult albumin, a single class of binding sites was observed for diazepam and digitoxin, whereas two classes of binding sites were observed for salicylic acid. The number of binding sites (n, moles of drug per mole of albumin) for fetal and adult albumin was 0.83 and 1.02 for diazepam and 0.014 and 0.018 for digitoxin, respectively. For salicylic acid, n was 1.45 (fetal albumin) and 1.55 (adult albumin) for the higher affinity site, and 3.06 (fetal albumin) and 3.27 (adult albumin) for the lower affinity site. The association constant (Ka, M-1) for diazepam was 1.36 x 10(5) (fetal albumin) and 1.00 x 10(5) (adult albumin) and that for digitoxin was 4.12 x 10(6) (fetal albumin) and 2.7 x 10(6) (adult albumin). For salicylic acid, Ka was 38.4 x 10(3) (fetal albumin) and 35.8 x 10(3) (adult albumin) for the higher affinity site, and 2.7 x 10(3) (fetal albumin) and 4.3 x 10(3) (adult albumin) for the lower affinity site. This work shows that fetal and adult albumin have similar binding properties and corroborates our previous findings with furosemide.
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PMID:Binding of diazepam, salicylic acid and digitoxin to albumin isolated from fetal and adult serum. 181 15

Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.
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PMID:Binding of furosemide to albumin isolated from human fetal and adult serum. 187 50

Tritium-labeled digitoxin, digitoxigenin, digoxin, and digoxigenin of established purity and chemcal authenticity were used to study the binding of these compounds to human plasma proteins. 97% of digitoxin in plasma was nondialyzable. Continuous flow paper electrophoresis of plasma containing digitoxin and dialysis experiments in which human serum albumin competed for the glycoside with plasma or plasma protein fractions demonstrated that digitoxin was almost exclusively bound by albumin. Equilibrium dialyses revealed that the interaction was characterized by a single binding site on the albumin molecule and an association constant of 9.62 x 10(4) liter/mole at 37 degrees C. At 1 degrees C the association constant was 4.64 x 10(4) liter/mole. The interaction therefore was endothermic; the gain in enthalpy of 3.5 kcal/mole and the free energy change of - 7.06 kcal/mole was derived from a large change in entropy of 33.8 cal/mole per degrees K. The direction of these thermodynamic changes suggested the formation of a hydrophobic bond between digitoxin and albumin. Quenching of the fluorescence of albumin by digitoxin indicated that the conformation of albumin was altered by the binding process.Digitoxigenin, its mono- and didigitoxosides, digoxin, and digoxigenin competed with digitoxn for its binding site on albumin. The affinity of the mono- and didigitoxosides for the site was equal to that of digitoxin, but that of digitoxigenin was only one-third as great. The ability of the digitoxose residues of the glycosides to enhance binding to albumin was also observed with digoxin, which was more extensively bound by the protein than digoxigenin. At concentrations of 2 mug/ml or less in plasma, only 23% of digoxin was bound. Albumin, which interacted with digoxin with an apparent association constant of 9 x 10(2) liter/mole at 37 degrees C, was entirely responsible for the binding. Lowering the temperature from 37 degrees to 1 degrees C decreased the fraction of digoxin bound to albumin by two-thirds. The marked difference in avidity of digitoxin and digoxin for serum albumin is reflected by the higher plasma concentrations, lower rate of urinary excretion, and longer half-time of digitoxin as compared to those of digoxin when these compounds are administered to man.
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PMID:Binding of digitoxin and some related cardenolides to human plasma proteins. 577 Nov 86

A comparison has been made between the conversion of (32)P-labeled lysophosphatidyl ethanolamine (LPE) and lysophosphatidyl choline (LPC) to their respective acylated and deacylated derivatives by homogenates of rabbit polymorphonuclear leukocytes and alveolar macrophages. Synthesis of PE by both homogenates and of PC by macrophage homogenates proceeded to about the same extent and is attributed to direct acylation of the lyso compounds. At higher LPC concentrations formation of PC by leukocytes is far greater than by macrophages. The mechanism of this enhanced synthesis of PC, which is brought out by higher substrate concentrations, is believed to be a transfer of the acyl group of one LPC molecule to another. Under optimal conditions macrophage homogenates deacylated LPE to a greater extent than LPC, while the reverse was true for leukocyte homogenates. Albumin inhibited deacylation of LPC and its conversion to PC by leukocytes, perhaps by binding the substrate (2 moles of LPC per mole of albumin). Other effects of albumin-stimulation of deacylation and acylation of LPE by macrophages, inhibition of deacylation and acylation of LPE by leukocytes-remain unexplained.
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PMID:Metabolism of lysophosphatidyl ethanolamine and lysophosphatidyl choline by homogenates of rabbit polymorphonuclear leukocytes and alveolar macrophages. 603 2

Plasma membrane isolated from rat sperm cells after incubation in vitro had a significantly lower cholesterol/phospholipid mole ratio when the medium contained serum albumin. Transfer of albumin-bound phospholipids to the membrane can largely account for this effect. The result is broadly consistent with a previously proposed model for albumin-induced destabilization of sperm membrane (capacitation) and its reversal by seminal plasma membrane vesicles. Albumin also decreased sialic acid and, more specifically, ganglioside levels, presumably by promoting release of sperm neuraminidase. Cholesteryl ester comprised up to 0.5 mol/mol of cholesterol in these plasma membrane preparations.
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PMID:Studies on the mechanism of capacitation: albumin-mediated changes in plasma membrane lipids during in vitro incubation of rat sperm cells. 644 58

A model system was developed to (a) reflect the chemical attributes of the microenvironment involved in albumin-eicosanoid interactions and (b) determine the effects of other ligands on these interactions. Albumin-dependent modulation of prostaglandin stability was chosen as the basis for this system. 15-Ketoprostaglandin E2 (PGE2) was evaluated as a model ligand because under special conditions it decomposes with formation of a visible chromophore. Human serum albumin, in a concentration-dependent fashion, catalyzed the dehydration of 15-keto-PGE2 with the concurrent generation of this chromophore (lambda max = 505 nm, epsilon = 35,000). Since chromophore production from 15-keto-PGE2 in albumin-free solution occurs only at pH greater than 10, the results suggest that albumin-eicosanoid interactions involve a microenvironment with alkaline attributes. The effect of other ligands on albumin-15-keto-prostaglandin E2 interactions was determined by monitoring their ability to inhibit the spectral component of these interactions. Inhibition correlated with an affinity for specific binding sites on albumin. At mole ratios of ligand/albumin below 1, only phenylbutazone, its analogs, and warfarin inhibited chromophore development. Other ligands including fatty acids, steroids, tryptophan, and drugs with an affinity for other binding sites were ineffective inhibitors.
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PMID:Albumin-eicosanoid interactions. A model system to determine their attributes and inhibition. 669 91

1. The transport of ferritin molecules by endothelial cell vesicles has been quantitatively investigated by electron microscopy. Single mesenteric capillaries of pithed frogs were perfused with solutions containing 6.7 g ferritin 100 ml.-1 for known periods before fixation in situ with osmium tetroxide. 2. Two series of experiments were carried out: in the first series the perfusate contained bovine serum albumin (1.0 g 100 ml.-1); in the second series the perfusate contained no protein other than the ferritin. To assess the molecular radius of ferritin in solution, the free diffusion coefficient of ferritin was measured in the presence and absence of albumin. 3. The free diffusion coefficient of ferritin in saline solution (110 m-mole 1.-1) was found to be 0.35 X 10(-6) cm2 sec-1 at 21 degrees C and was not affected by the presence of bovine serum albumin. This indicates that there is no significant binding of albumin to ferritin in solution and yields a value for the Stokes-Einstein radius of ferritin of 6.1 nm. 4. In all perfusion experiments the percentage of luminal vesicles containing ferritin exceeded the percentage of labelled cytoplasmic vesicles, which in turn exceeded the percentage of labelled abluminal vesicles. 5. Labelling of all vesicle populations was seen after perfusions lasting less than 1 sec. At this time luminal vesicles were more heavily labelled in the absence of albumin. 6. The labelling of luminal vesicles increased with lengthening perfusion times up to 30-40 sec, after which steady levels of labelling were achieved. The rate of rise in luminal labelling and the steady-state levels reached were both greater in the absence of albumin. By contrast cytoplasmic labelling increased above its initial value only after perfusions of longer than 10 sec. 7. In the steady state, labelled cytoplasmic vesicles contained, on average, fewer ferritin molecules than labelled luminal vesicles. This finding is inconsistent with translocation of labelled luminal vesicles across the cell. 8. It is suggested that the early constant labelling of cytoplasmic and abluminal vesicles is consistent with the existence of vesicular channels. Later cytoplasmic labelling may result from the transient fusion of cytoplasmic vesicles with labelled luminal vesicles for periods long enough to allow mixing of vesicular contents. Albumin may affect vesicular transport by its interaction with the endothelial glycocalyx.
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PMID:The role of vesicles in the transport of ferritin through frog endothelium. 697 16

We determined the effect of vertebrate albumins on the stability of several physiologically relevant prostaglandins. All naturally occurring prostaglandins with beta-hydroxy ketone group decomposed by first-order kinetics, dependent on the albumin concentration in 0.1 M, pH 7.4, buffer at 37 degrees C. Even subphysiological levels of albumin (1-20 mg/mL) significantly reduced the stability of these compounds in vitro. The prostaglandins with a beta-hydroxy ketone responded to albumin in the order of their intrinsic stability; namely, less stable compounds were more susceptible. The destructive effect of albumin was nearly maximal at a 1:1 mole ratio of albumin (20 mg/mL):prostaglandin (100 micrograms/mL). Albumin had no destructive effect on prostaglandins without a beta-hydroxy ketone. Albumins from different vertebrates varied in destructive severity, but all were effective. Near neutrality, in the absence of albumin, decomposition of E-type prostaglandins was practically suspended at the dehydration stage. In the presence of albumin, dehydration was accompanied by rapid isomerization reactions (e.g., PGA1 leads to PGB1) that occur only at an elevated pH. The results suggest that albumin sequesters prostaglandins to one principal binding site and exposes them to its associated highly alkaline microenvironment. This results in a uniform and predictable influence on prostaglandin stability. Our proposed model system successfully reconciles apparently anomalous or contradictory reports regarding the effect of albumin on prostaglandin stability.
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PMID:Albumin-lipid interactions: prostaglandin stability as a probe for characterizing binding sites on vertebrate albumins. 730

Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant syndrome in which clinically euthyroid patients have elevated total thyroxine levels. These high serum thyroxine levels are traceable to altered binding of thyroxine to the patient's albumin. Albumin from FDH patients and normal volunteers have been purified. Reverse-phase and ion-exchange high performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis on the FDH-human serum albumin (HSA) samples show a single band that comigrates with normal HSA. In both protein solutions the intrinsic fluorescence, upon 280 nm excitation, is predominantly due to the single tryptophan residue. The quantum yield of this intrinsic fluorescence in the FDH-HSA solutions is, however, reduced relative to that of HSA. Furthermore, the "average" lifetime value of the tryptophan emission in the FDH-HSA sample is less than that of normal HSA, consistent with its reduced quantum yield. The binding of thyroxine to both albumins effectively quenches the tryptophan emission probably via a nonradiative energy transfer mechanism. Time-resolved data suggest that the albumin from the dysalbuminemic patients is actually an approximately equimolar mixture of normal HSA and FDH-HSA indicative of heterologous expression. Quenching of the intrinsic HSA and FDH-HSA fluorescence by serial additions of thyroxine showed enhanced quenching of FDH-HSA relative to HSA at any T4 to albumin mole ratio, therefore supporting earlier reports of increased thyroxine affinity to FDH-HSA.
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PMID:Fluorescence investigations of albumin from patients with familial dysalbuminemic hyperthyroxinemia. 847 73


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