A circular dichroism (CD) study of the consecutive binding of serum albumin to bilirubin. Possible implications for the bilirubin level

Blaha, Gregor; Siam, Monira; Lehner, Harald

doi:10.1039/a607825g

Cited by 10 publications

(14 citation statements)

References 25 publications

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“…43 Indeed, there is little evidence that precipitates of bilirubin commonly exist in icteric plasma (or other aqueous tissues of the body; exceptions being the renal papillary tip of the Gunn rat, 44 infected bile or tissues of terminally ill patients with kernicterus 45 ). Even in Crigler-Najjar patients with very high bilirubin levels or homozygous Gunn rats there is no evidence of precipitation or aggregation of bilirubin in the circulation, observations that are consistent with circular dichroism studies on serum albumin-bilirubin binding by Lehner and colleagues 46 and their conclusion that 'even at pathophysiological total concentrations of bilirubin, the unbound portion does not exceed the solubility limit'. Case series that include several neonates with peak TSB levels of greater than 40 mg per 100 ml and as high as 59.9 mg per 100 ml, 26,47 as well as peroxidase measurements of serum B F in human newborns lend credence to this speculation.…”

supporting

confidence: 78%

Calculated free bilirubin levels and neurotoxicity

2009

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Although most bilirubin in the circulation is bound to albumin, a relatively small fraction remains unbound. The concentration of this 'free' bilirubin (B F ) is believed to dictate the biologic effects of bilirubin in jaundiced newborns, including its neurotoxicity. The threshold at which B F produces changes in cellular function culminating in permanent cell injury and cell death has been the subject of considerable debate. The objective of this study was to compare calculated central nervous system (CNS) B F levels in Gunn rat pups during (i) peak postnatal hyperbilirubinemia and (ii) sulfadimethoxine-induced acute bilirubin encephalopathy (ABE) previously reported from our laboratory with those predicted in human neonates with peak total serum bilirubin (TSB) levels of 35 mg per 100 ml (599 mmol l À1 ), a clinical cohort that often evidence moderate-to-severe adverse post-icteric neurodevelopmental sequelae. Homozygous j/j Gunn rat pups with neonatal hyperbilirubinemia due to a deficiency of the bilirubin conjugating enzyme uridine-diphosphate-glucuronosyl transferase 1A1 were studied along with non-jaundiced littermate heterozygous J/j controls. Sulfadimethoxine was used to displace bilirubin from albumin in hyperbilirubinemic j/j Gunn rat pups to increase their brain bilirubin content and induce ABE. Calculated Gunn rat CNS B F levels were determined as a function of genotype, sulfadimethoxine exposure and albumin-bilirubin binding constant. These data were compared with the human CNS B F predicted from the calculated serum B F in human neonates with a TSB of 35 mg per 100 ml as a function of albumin-bilirubin binding constant, albumin concentration and the assumption that at this hazardous bilirubin level there may be rapid equilibration of B F between serum and brain. There was a large gap between the upper limit of the calculated CNS B F 95% confidence interval (CI) range in non-jaundiced J/j pups (for example, 112 nM at k ¼ 9.2 l mmol À1 ) and the lower limit seen in the saline-treated hyperbilirubinemic j/j pups (556 nM at k ¼ 9.2 l mmol À1 ) as well as between the upper limit in saline-treated hyperbilirubinemic j/j pups (1110 nM at k ¼ 9.2 l mmol À1 ) and the lower limit seen in sulfadimethoxine-treated jaundiced j/j littermates (3461 nM at k ¼ 9.2 l mmol À1 ). There was considerable overlap and remarkable similarity between the predicted human CNS B F values at a TSB of 35 mg per 100 ml for a range of reported human serum bilirubin-albumin binding constants and albumin concentrations, and those calculated for saline-treated hyperbilirubinemic j/j Gunn rat pups. This exercise yielded strikingly similar apparent calculated neurotoxic B F levels for Gunn rat pups and human neonates rather than orders of magnitude differences that might have been predicted at the outset and add to a growing literature aimed at defining clinically germane neurotoxic B F thresholds.

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confidence: 78%

Calculated free bilirubin levels and neurotoxicity

2009

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“…It was found that the aggregate of BR-BSA complex is clearly larger than the BR micro crystal in size at MR being 1, where the BSA concentration is much lower than that in a physiological environment, but other smaller aggregates could not be observed by a 40× objective. This result suggests that under some conditions the aggregates of the BR-BSA complex may be formed in biological interfaces and provoke diseases, 6 as well as in an unbound BR micro crystal. The BSA molecule has three domains, each having two subdomains; specialized ligand-binding cavities are located in subdomains IIA and IIIA (the high affinity site for BR resides within IIA).…”

Section: Resonance Raman Spectra Of the Aggregate Of The Br-bsa Complmentioning

confidence: 93%

“…15,16 According to the exciton chirality rule, 15,16 dipyrrinone-dipyrrinone intramolecular exciton interactions (exciton coupling) coming from either of the BR conformation of (P+) and (M-) can generate CD spectra with opposite signs. It is possible that the equilibrium racemic state is broken and an induced optical activity can be generated, [3][4][5][6][7][8] because either enantiomer of the (P+) and (M-) forms of BR binds with an external chiral protein, such as BSA.…”

Section: Introductionmentioning

confidence: 99%

“…If the body does not produce an adequate amount of albumin, BR is sequestered directly under the skin, and even provoke BR encephalopathy by passing the blood-brain barrier and penetrating the phospholipid membrane of neurons. Although BR and its complex with serum albumin (SA) have been extensively investigated in bulk phases, [2][3][4][5][6][7][8][9][10][11] the complexation of BR with SA has never been studied at a liquid/liquid interface, which is recognized as being a model of a biological membrane, 12 and as a specific reaction field in the solvent extraction of metal ions. 13 In the present work, resonance Raman spectroscopy was applied to measure the microenvironment of an interfacial complex of BR with bovine serum albumin (BSA) and the aggregate of the complex at the organic/water interface.…”

Section: Introductionmentioning

confidence: 99%

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Resonance Raman Spectroscopic Study on Chiral Aggregation of Bilirubin-Bovine Serum Albumin Complex Formed at Liquid/Liquid Interface

Yin

Watarai

2007

ANAL. SCI.

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Resonance Raman spectroscopy assisted by centrifugal liquid membrane/circular dichroism (CLM-CD) and UV/Vis absorption spectroscopies was applied to measure the binding state of bilirubin (BR) in the complex with bovine serum albumin (BSA) formed at a heptane/water interface. The bisignate Cotton effects in the interfacial CD spectra and the red shift and linewidth increase of the BR absorption band around 450 nm indicated the formation of the BR-BSA complex at the interface and the chiral conversion of BR molecules in the aggregates. The resonance Raman spectra of BR observed at the interface suggested that the interfacial BR-BSA complex formed during the initial 15 min after the contact of the two phases had a similar structure with that in solution, but after 15 min were forming aggregates coexisting with solid micro-particles. These experimental results strongly suggested that the chiral interconversion of BR from (P+) conformation to (M-) conformation in the interfacial complex was accompanied by aggregation of the BR-BSA complexes. In the present study, resonance Raman microscopic spectrometry was proved to be highly useful for characterizing the solid like aggregate formed at the liquid/liquid interface. 3 The dashed lines show intramolecular hydrogen bondings that link the dipyrrinones to opposing propionic acids. θ denotes the dihedral angle (see the text for details).

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“…Because of the crucial role of pigment complexation in neutralization of their toxicity, the interaction of BR with serum albumin and its model systems is one of the most studied albumin-ligand interactions. [46][47][48] VCD was used 49,50 in studies of the structural aspects of the interactions of bile pigments in model systems. Because of fast racemization of pure pigments in solution, an appropriate chiral recognition must be involved prior to a spectral study by chiroptical methods.…”

Section: Biointeractions Of Bile Pigmentsmentioning

confidence: 99%

Bioinspired interactions studied by vibrational circular dichroism

Urbanová

2009

Chirality

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Vibrational circular dichroism (VCD) spectra are reliable indicators of the spatial structure of chiral molecules. The specific and characteristic feature of vibrational spectroscopy, and therefore also of VCD, where the energy of some vibrational modes is predominantly focused to a specific part of the molecule, enables monitoring both the structure of the molecule dissolved in different solvents and under different physicochemical conditions and molecular interactions. This minireview deals with recent contributions covering structural information on the bioinspired interactions obtained by means of VCD, especially in the following areas: interaction of DNA with biomolecules and biogenic metals, guanine tetramers and quadruplexes, biointeractions of bile pigments, and polypeptide and protein interactions with other biomolecules.

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A circular dichroism (CD) study of the consecutive binding of serum albumin to bilirubin. Possible implications for the bilirubin level

Cited by 10 publications

References 25 publications

Calculated free bilirubin levels and neurotoxicity

Calculated free bilirubin levels and neurotoxicity

Resonance Raman Spectroscopic Study on Chiral Aggregation of Bilirubin-Bovine Serum Albumin Complex Formed at Liquid/Liquid Interface

Bioinspired interactions studied by vibrational circular dichroism

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