Conformation of bilirubin and biliverdin in their complexes with serum albumin

Blauer, G.; Wagnière, G.

doi:10.1021/ja00840a057

Cited by 146 publications

(52 citation statements)

References 8 publications

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“…Thus, this process represents an asymmetric transformation of the first kind or enantiomerization [15]. A similar mechanism has been suggested for the intense CD in bilirubin and biliverdin induced by binding to serum albumen [16,17].…”

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confidence: 66%

Solvent Induced Circular Dichroism in Conformational Analysis: Bile Pigments

Lehner

Krauss²,

Scheer³

1981

Zeitschrift Für Naturforschung B

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Abstract The applicability of solvent induced circular dichroism (SICD) for the conformational analysis of bile pigments has been investigated. The S-(-)-ethyl lactate induced rotational strengths for octaethylbilindion (4) and its dihydroderivative 5 are remarkably high. Related compounds, e.g. the isomeric purpurines 1 and 2 and formyltripyrrinon 3 exhibit an optical activity which is smaller by more than one order of magnitude. 1-3 are essentially free from steric strain so that a flat arrangement of the chromophore is most likely. On the other hand the closed conformations of 4 and 5 experience considerable steric repulsion of their terminal rings, so that a helical topology is energetically favoured. This distinction is reflected in the magnitude of the SICD observed and demonstrates its applicability for the conformational analysis of bile pigments.

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mentioning

confidence: 66%

Solvent Induced Circular Dichroism in Conformational Analysis: Bile Pigments

Lehner

Krauss²,

Scheer³

1981

Zeitschrift Für Naturforschung B

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“…At neutral and alkaline pH, complexed bilirubin forms a right-handed helix. This converts into a left-handed helix when the pH is lowered to acidic values (29). Fig.…”

Section: Resultsmentioning

confidence: 98%

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria

Gitzelmann-Cumarasamy

Gitzelmann²,

Wilson

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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The existence of a functionally immature fetal albumin has been postulated to explain the reduced ability of newborn plasma to bind bilirubin and various drugs. In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and in their resistance to alkali and proteolytic enzymes. However, the interpretation of these findings has since been questioned. To resolve this controversy, we have purified to homogeneity human serum albumins from pooled umbilical cord and adult donor plasma. The two albumins were compared and found to be indistinguishable by polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, as well as by immunoelectrophoresis and double immunodiffusion using specific antibodies against both albumins. Furthermore, the amino acid compositions, the aminoterminal sequence (Asp-Ala-His-Lys-Ser-Glu-Val-Ala-), the carboxy terminus (Leu), and the peptide fingerprints were identical in the two albumins. No significant differences were found by circular dichroism in the ultraviolet (200-350 nm). Binding studies with bilirubin showed association constants of 3.7 + 0.7 X 107 M-1 for cord and 2.9 : 0.3 X 107 M-' for adult albumin, respectively. The circular dichroic spectra of 1:1 bilirubin-albumin complexes showed considerable variation between the batches but were not significantly different. The only difference was found in the fluorescence spectra of the bilirubin-albumin complexes, in which complexes with adult albumin showed only 75% of the relative fluorescence exhibited with cord albumin. The combined results nevertheless strongly indicate that fetal and adult albumins are very similar, if not identical. Human serum albumin is an almost universal carrier for a host of metabolites and drugs (1). As such it plays a central role in the regulation of their activity or toxicity. This is of particular significance in neonatal medicine because newborns, with their immature detoxifying mechanisms (for review see ref.2), are highly susceptible to various toxic agents. A well-known example is bilirubin encephalopathy resulting from neonatal jaundice.During clinical studies it was observed that newborn serum has a lower ability to bind bilirubin and drugs than adult serum does (refs. 3 and 4 and references cited therein). To explain these observations, the existence of a fetal type of albumin, analogous to hemoglobin F, was postulated. In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and to vary in resistance to alkali and proteolytic enzymes (5, 6). However, authors of subsequent papers questioned the existence of a functionally immature albumin and attributed the reduced binding of newborn serum to competitive binding by increased concentrations of certain metabolites such as arachidonic acid and hematin (7-11).To resolve this controversy, we purified cord and adult albumin...

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“…Whether the hydrogen bonds are absolutely intramolecular between the two dipyrrole halves of bilirubin, or intermolecular, involving either dipyrrole moiety and the peptide and other polar groups of albumin, is not clear. The observed induced-CD spectra are characteristic of those produced by exciton coupling of the transition moments of the two chromophores of a bilirubin molecule, each having strongly allowed ultraviolet-visible absorption in the region 400-450 nm and little orbital overlap between them (Blauer and Wagniere, 1975 ;Harada and Nakanishi, 1983;Byun and Lightner, 1991 ;Person et al, 1994). Maximum exciton interaction between the intense long-wavelength electronic transitions of each dipyrrinone occurs when the chromophores are held about 90" apart, where interchrornophoric orbital interaction (homoconjugation) is minimized (Blauer and Wagniere, 1975 ;Byun and Lightner, 1991 ;Person et al, 1994).…”

Section: Discussionmentioning

confidence: 96%

Spectroscopic Probes of the Individual and Combined Effects of Triton X‐100 and Chloroform on Serum Albumins and Serum‐Albumin · Bilirubin Complexes

Patra

Pal

1997

European Journal of Biochemistry

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The effects of the non-ionic surfactant Triton X-100 on the biphasic induced CD spectra of bilirubin complexes of human and bovine serum albumins (HSA and BSA) are divergent. While Triton X-100 inverts the induced CD spectrum of HSA . bilirubin, this surfactant enhances the ellipticity values of induced CD of BSA . bilirubin without inversion. The effect of Triton X-100 on the characteristic ultraviolet-CD spectra of the albumins are similar; both the albumins are denatured from their native globular structures. The anionic surfactant SDS, unlike non-ionic Triton X-100, dislodges the ligand from its protein complexes, indicating that both electrostatic and hydrophobic forces are involved in binding of bilirubin to the albumins.The aprotic solvent chloroform inverts the biphasic induced CD spectra of HSA . bilirubin and BSA . bilirubin, whereas CHCI, has relatively little effect on the ultraviolet CD spectra of the albumins. The combined effect of Triton X-I00 and CHCI, shows that the effect of CHCI, predominates over that of Triton X-100. The perturbing effects of Triton X-100 and CHCI, on the CD or induced CD spectra of the proteins or their bilirubin complexes are reversible, and independent of the order in which components were added. The observations suggest that the denaturation of the albumins by Triton X-100 or solvation of CHCI, within albumins markedly alter the internal topography or dynamics of the receptor sites, triggering alterations of the chirality of the bound pigment in sign and/or magnitude.Keywords : bilirubin ; serum albumin ; induced circular dichroism ; enantioselection ; denaturation.Bilirubin, the end product of heme metabolism, is the cytotoxic and neurotoxic pigment of jaundice (Rimington, 1957 ;With, 1968; Brodersen, 1979a;Semba and Kato, 1982;Meisel and Jahr, 1991 ; Ostrow, 1993, 1996;Ostrow et al., 1994;Hansen, 1994). The molecule is a substituted tetrapyrrole dicarboxylic acid. It consists of two dipyrrole halves joined by CH, group. The two dipyrrole halves are intramolecularly hydrogen bonded, between the COOH group of each half and the lactam (NH-C=O) and NH groups of the other half, imposing folded biplanar ridge-tile interconverting enantiomeric conformations (Bonnett et al., 1976(Bonnett et al., , 1978Kaplan and Navon, 1983;Trull et al., 1983Trull et al., , 1987Person et al., 1994;Nogles and Lightner, 1995).Due to the presence of aromatic domains (rings) and imposed conformational restriction, the molecule is hydrophobic in nature, which is unusual for a dicarboxylic acid (Bonnett et al., 1976(Bonnett et al., , 1978 Brodersen, 197913; Lightner and McDonagh, 1984;Lightner et al., 1996). In plasma the pigment is rendered soluble on binding to albumin, the most abundant serum protein, forming a non-covalent-association complex, and is transported to the liver for glucuronidation and subsequent excretion (Ostrow et al., 1963;Cooke and Roberts, 1969; Watson, 1962; Robinson and Rapoport, 1987;Zucker et al., 1994Zucker et al., , 1995. Competitive binding studies with other amphiphi...

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Conformation of bilirubin and biliverdin in their complexes with serum albumin

Cited by 146 publications

References 8 publications

Solvent Induced Circular Dichroism in Conformational Analysis: Bile Pigments

Solvent Induced Circular Dichroism in Conformational Analysis: Bile Pigments

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria

Spectroscopic Probes of the Individual and Combined Effects of Triton X‐100 and Chloroform on Serum Albumins and Serum‐Albumin · Bilirubin Complexes

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