Relative affinities of bilirubin for serum albumins from different species

Blauer, G.; Lavie, E.; Silfen, J.

doi:10.1016/0005-2795(77)90214-8

Cited by 24 publications

(10 citation statements)

References 7 publications

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“…However, a well-defined induced CD spectrum was observed upon binding to the stereo-specific site on HSA. 8,14,20,21,36 Bilirubin exists in aqueous solution as an isoenergetic mixture of two conformational isomers of P-and M-helicity. [36][37][38] The appearance of a bisegnate CD spectrum when bilirubin binds to HSA has been interpreted as HSA bound bilirubin adopting a prevailing conformation of P helicity.…”

Section: Measurementsmentioning

confidence: 99%

“…42 The obtained affinity constant determined for the HSA/PBU complex is also in agreement with the previous reports using CD spectroscopy. 14 The affinity constant values determined by CD spectroscopy may differ from those obtained by other methods, because the CD technique selectively monitors only binding to the stereoselective-binding sites.…”

Section: 32mentioning

confidence: 99%

“…Many techniques are suitable to determine the binding parameters of drugs to serum albumins, such as equilibrium dialysis, 1 biochromatography, [8][9][10][11][12] spectroscopy, [13][14][15][16][17][18][19][20][21][22] and optical biosensors. [23][24][25] This study used CD (circular dichroism) spectroscopy not only to determine the affinity constants of selected ligands to albumins from different species, but also to gain information on the stereochemistry of the bound drug.…”

Section: Introductionmentioning

confidence: 99%

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Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Pistolozzi

Bertucci

2008

Chirality

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Drug binding to albumins from different mammalian species was investigated to disclose evidence of species-dependent stereoselectivity in drug-binding processes and affinities. This aspect is important for evaluating the reliability of extrapolating distribution data among species. The circular dichroism (CD) signal induced by drug binding to the albumins [human serum albumin (HSA), bovine serum albumin (BSA), rat serum albumin (RSA), and dog serum albumin (DSA)] were measured and analyzed. The binding of selected drugs and metabolites to HSA significantly differed from the binding to the other albumins in terms of affinity and conformation of the bound ligands. In particular, phenylbutazone, a marker of site one on HSA, showed a higher affinity for binding to BSA with respect to RSA, HSA, and DSA, respectively. In the case of diazepam, a marker of site two on HSA, the affinity decreased in order from HSA to DSA, RSA, and BSA. The induced CD spectra were similar in terms of energy and band signs, suggesting almost the same conformation for the bound drug to the different albumins. Stereoselectivity was high for the binding of ketoprofen to HSA and RSA. A different sign was observed for the CD spectra induced by the drug to the two albumins because of the prevalence of a different conformation of the bound drug. Interestingly, the same induced CD spectra were obtained using either the racemic form or the (S)-enantiomer. Finally, significant differences were observed in the affinity of bilirubin, being highest for BSA, then decreasing for RSA, HSA, and DSA. A more complex conformational equilibrium was observed for bound bilirubin.

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Section: Measurementsmentioning

confidence: 99%

Section: 32mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Pistolozzi

Bertucci

2008

Chirality

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“…Firstly, it must be pointed out that some toxins may bind to albumin in different molar ratios: it is generally agreed that the albumin molecule has one high affinity and one (or two) low affinity binding sites for bilirubin [19,20]; also for tryptophan, an analogous multiplicity of binding sites seems to exist [21][22][23]. Anyway, binding constants to secondary sites are in general much lower than those of the primary site (values of 5 − 7 × 10 7 M −1 and 4 − 5 × 10 6 M −1 are reported in literature for the binding constants of bilirubin to the first and second site of human serum albumin, respectively [19,20]), therefore, at least for high albumin-totoxin molar ratios in the liquid phase, formation of complexes involving secondary sites may be neglected.…”

Section: Mathematical Modelmentioning

confidence: 99%

Bilirubin and tryptophan adsorption in albumin-containing solutions

Annesini

Carlo

Piemonte

et al. 2008

Biochemical Engineering Journal

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“…The binding constant of HSA has been estimated to be 2-13 times greater than that of BSA (11)(12)(13). Considerable variation in serum binding of bilirubin has been reported in newborn infants (2).…”

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confidence: 99%

Factors Affecting the Binding of Bilirubin to Serum Albumins: Validation and Application of the Peroxidase Method

et al. 2006

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ABSTRACT:The unbound "free" bilirubin concentration (B f ), not the total bilirubin concentration, is the critical determinant of cellular uptake and toxicity of bilirubin. We compared B f measured by a modified peroxidase method with published data obtained with ultrafiltration and examined conditions that affect the affinity (K F ) of human (HSA) and bovine (BSA) serum albumin for bilirubin. The peroxidase and ultrafiltration methods yielded similar K F values that decreased with increasing HSA concentration and the presence of 50 mM chloride. When related to ionic strength, inhibition of BSAbilirubin binding by chloride, bromide, and sulfate were similar, whereas phosphate buffer had a smaller effect. K F was lower at 37°C than at 25°C for HSA but not for BSA. K F for BSA was similar at pH 7.4 and 8. T he unbound ("free") concentration of unconjugated bilirubin (B f ) in plasma, although less than 0.1% of total bilirubin concentration, is the principal determinant of tissue uptake and toxicity of bilirubin, and plays a critical role in the pathogenesis of bilirubin encephalopathy in jaundiced newborns (1,2) and in patients with Crigler Najjar disease (3). Notwithstanding its biologic significance, B f has rarely been measured in either clinical evaluation of jaundiced newborns or in vitro studies of bilirubin effects and toxicity. This avoidance is due in part to the perceived complexity of B f assays and scepticism regarding their clinical value or accuracy (4 -6).Bilirubin-albumin binding has been studied using a variety of techniques, including fluorescent quenching, bilirubin fluorescence, circular dichroism, Sephadex gel filtration, optical rotary dispersion, dialysis, ultrafiltration, spectrophotometry, and enzymatic oxidation of bilirubin (peroxidase method). Reported association constants for HSA range from 6.7 ϫ 10 6 M Ϫ1 to Ͼ10 8 M Ϫ1 (7-10). The binding constant of HSA has been estimated to be 2-13 times greater than that of BSA (11-13). Considerable variation in serum binding of bilirubin has been reported in newborn infants (2). These differences may be due to direct binding competitors (e.g. sulfonamides), allosteric effects, electrolyte environment, or simply the assay technique, e.g. serum sample dilution (14).The dependency of bilirubin binding affinity on HSA concentration as well as chloride concentration was demonstrated by Weisiger et al. (15) using a complicated procedure in which binding affinity of 14 C-bilirubin was calculated after the sequential removal of labeled impurities by serial ultrafiltration. A more practical technique for measuring B f in clinical or laboratory settings was developed by Jacobsen and Wennberg (16) based on the observation that albumin-binding protects bilirubin from oxidation by HRP. Ahlfors (14,17) has modified the peroxidase method, emphasizing the need to measure B f with two or more HRP concentrations and under the same conditions and albumin concentrations existing in plasma or incubation medium.In this investigation, we replicated and extended the exp...

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Relative affinities of bilirubin for serum albumins from different species

Cited by 24 publications

References 7 publications

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

Bilirubin and tryptophan adsorption in albumin-containing solutions

Factors Affecting the Binding of Bilirubin to Serum Albumins: Validation and Application of the Peroxidase Method

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