Acidity in bile acid systems

Fini, Adamo; Feroci, Giorgio; Roda, Aldo

doi:10.1016/s0277-5387(02)00968-3

Cited by 19 publications

(16 citation statements)

References 33 publications

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“…The major primary BS in humans are chenodeoxycholate (CDCA) with 2 hydroxyl groups, and cholate (CA) with 3 hydroxyl groups. The carboxyl group of BS is usually conjugated with glycine or taurine, leading to an increase in their acidity (decrease in pK a from about 5 to 4 and below 2, for conjugation with glycine and taurine, respectively) and therefore to an increase in the fraction of the ionized form (Carey and Small, 1972; Fini et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

et al. 2019

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Bile salts (BS) are biosurfactants crucial for emulsification and intestinal absorption of cholesterol and other hydrophobic compounds such as vitamins and fatty acids. Interaction of BS with lipid bilayers is important for understanding their effects on membranes properties. The latter have relevance in passive diffusion processes through intestinal epithelium such as reabsorption of BS, as well as their degree of toxicity to intestinal flora and their potential applications in drug delivery. In this work, we used molecular dynamics simulations to address at the atomic scale the interactions of cholate, deoxycholate, and chenodeoxycholate, as well as their glycine conjugates with POPC bilayers. In this set of BS, variation of three structural aspects was addressed, namely conjugation with glycine, number and position of hydroxyl substituents, and ionization state. From atomistic simulations, the location and orientation of BS inside the bilayer, and their specific interactions with water and host lipid, such as hydrogen bonding and ion-pair formation, were studied in detail. Membrane properties were also investigated to obtain information on the degree of perturbation induced by the different BS. The results are described and related to a recent experimental study ( Coreta-Gomes et al., 2015 ). Differences in macroscopic membrane partition thermodynamics and translocation kinetics are rationalized in terms of the distinct structures and atomic-scale behavior of the bile salt species. In particular, the faster translocation of cholate is explained by its higher degree of local membrane perturbation. On the other hand, the relatively high partition of the polar glycine conjugates is related to the longer and more flexible side chain, which allows simultaneous efficient solvation of the ionized carboxylate and deep insertion of the ring system.

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Section: Introductionmentioning

confidence: 99%

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

et al. 2019

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“…The bile salts amphiphilicity originates from dissimilarities between the two faces of the steroid rings: the one containing the hydroxyl groups is defined as the a-face (concave side), while the one formed by the hydrocarbon skeleton is the b-face (convex side) [5]. The aggregation number of their micelles is generally low in comparison to the usual aliphatic surfactants (sodium dodecyl-sulfate), and micelles can increase their size and number as the bile salt concentration increases (usually up to 16 building units) [6]. The potentiometric titrations of cholic and deoxycholic salts were first done by Ekwall et al [7].…”

Section: Introductionmentioning

confidence: 99%

Determination of pK_a Values of Oxocholanoic Acids by Potentiometric Titration

Farkaš

Poša

Tepavčević

2014

J Surfact & Detergents

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The pKa and the maximum solubility values of cholic, deoxycholic salts and their oxo‐derivatives have been measured by the method of potentiometric titration. In the monomer phase (under the critical micellar concentration, CMC), the bile salts have different pKa values, as a result of their structural differences (the number of hydroxyl and oxo groups in the steroid skeleton) and different hydration properties of the acid anions. In the micellar phase (above the CMC), the bile salts have higher pKa values than in the monomer phase (under the CMC). This increase in the pKa values is greater in more hydrophobic bile salts (cholate and deoxycholate), than in less hydrophobic oxo derivatives, which can be explained by the different aggregation numbers of these bile salts. The oxo‐derivatives are more likely to form dimeric micelles, where the carboxylic groups are situated on the two sides of the micelle, not causing any electrostatic repulsion. In the more hydrophobic bile salts, aggregation numbers are higher, which causes electrostatic repulsion of the nearby situated carboxylic anions and consequential protonation of these anions (which leads to the stabilization of the micelle). The maximum solubility values are higher for the oxo‐derivatives. If the steroid skeleton of the bile salt is more hydrophobic, the capacity to solubilize the unionized bile acid is higher, i.e. a smaller amount of the bile acid anion is needed for the solubilization of the bile acid monomer. The oxo‐derivatives are less hydrophobic, but alongside their hydrophobicity, the structure of the micelle determines the solubilization capacities.

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“…Bile acids (BAs) are steroidal compounds synthesized in the liver during cholesterol metabolism, and their major structural components include a steroid nucleus with a side chain and carboxyl groups [1][2][3]. BAs are predominantly present in biological fluids in their ionized form.…”

Section: Introductionmentioning

confidence: 99%

“…BAs are predominantly present in biological fluids in their ionized form. The composition of BA in serum and urine varies with different physicochemical properties and the rate of intestinal absorption by the liver [2,4]. Its hepatic and intestinal metabolism can also be influenced by liver and gastrointestinal diseases.…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Derivatization of Bile Acids for Gas Chromatography/Mass Spectrometry Determination

Paiva

Menezes

Cardeal

2013

ISRN Analytical Chemistry

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Bile acids derived from cholesterol are produced in the liver, and their analysis is difficult due to their complex natures and their low concentrations in biological fluids. Mixtures of various derivatives, created via conventional heating, are used for such analyses. Microwave radiation is proposed to accelerate the derivatization process. This paper presents a mass fragmentation study and microwave-assisted derivatization (MAD) for the silylation of bile acids (cholic and ursodesoxycholic) prior to gas chromatography and mass spectrometry analysis. The derivatization was performed using the two-step process of methoximation and silylation. The reaction time, power, and quantity of N,O-bis-(trimethylsilyl) trifluoroacetamide (BSTFA) + 1% trimethylchlorosilane (TCMS) were optimized to improve the derivatization. The optimized derivatization conditions required 210 W for 3 min. The MAD method exhibited linearity with respect to cholic acid between 0.78 and 20.0 μg mL−1 with an LOQ of 0.23 μg mL−1 and a precision ranging from 1.08% to 9.32% CV. This optimized derivatization method is valid for the analysis of bile acids in different matrices.

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Acidity in bile acid systems

Cited by 19 publications

References 33 publications

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

Determination of pK_a Values of Oxocholanoic Acids by Potentiometric Titration

Microwave-Assisted Derivatization of Bile Acids for Gas Chromatography/Mass Spectrometry Determination

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Acidity in bile acid systems

Cited by 19 publications

References 33 publications

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

Determination of pKa Values of Oxocholanoic Acids by Potentiometric Titration

Microwave-Assisted Derivatization of Bile Acids for Gas Chromatography/Mass Spectrometry Determination

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Determination of pK_a Values of Oxocholanoic Acids by Potentiometric Titration