Photo-isomerization and oxidation of bilirubin in mammals is dependent on albumin binding
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26297581
DOI
10.1016/j.ab.2015.08.001
PII: S0003-2697(15)00377-2
Knihovny.cz E-zdroje
- Klíčová slova
- Antioxidant, Bilirubin conversion, Bilirubin–biliverdin reversible antioxidant redox cycle, Circular dichroism, Molecular docking, Photo-isomerization,
- MeSH
- bilirubin analogy a deriváty chemie metabolismus MeSH
- biliverdin analogy a deriváty chemie metabolismus MeSH
- cirkulární dichroismus MeSH
- fluorescenční spektrometrie MeSH
- fotochemické procesy * MeSH
- kompetitivní vazba MeSH
- lidé MeSH
- lidský sérový albumin MeSH
- ligandy MeSH
- molekulární konformace MeSH
- molekulární modely * MeSH
- oxidace-redukce MeSH
- sérový albumin chemie metabolismus MeSH
- simulace molekulového dockingu MeSH
- stereoizomerie MeSH
- taurin analogy a deriváty chemie metabolismus MeSH
- tryptofan chemie MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ALB protein, human MeSH Prohlížeč
- bilirubin ditaurine MeSH Prohlížeč
- bilirubin MeSH
- biliverdin MeSH
- lidský sérový albumin MeSH
- ligandy MeSH
- lumirubin MeSH Prohlížeč
- sérový albumin MeSH
- taurin MeSH
- tryptofan MeSH
- xanthobilirubic acid MeSH Prohlížeč
The bilirubin (BR) photo-conversion in the human body is a protein-dependent process; an effective photo-isomerization of the potentially neurotoxic Z,Z-BR as well as its oxidation to biliverdin in the antioxidant redox cycle is possible only when BR is bound on serum albumin. We present a novel analytical concept in the study of linear tetrapyrroles metabolic processes based on an in-depth mapping of binding sites in the structure of human serum albumin (HSA). A combination of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular modeling methods was used for recognition of the binding site for BR, its derivatives (mesobilirubin and bilirubin ditaurate), and the products of the photo-isomerization and oxidation (lumirubin, biliverdin, and xanthobilirubic acid) on HSA. The CD spectra and fluorescent quenching of the Trp-HSA were used to calculate the binding constants. The results of the CD displacement experiments performed with hemin were interpreted together with the findings of molecular docking performed on the pigment-HSA complexes. We estimated that Z,Z-BR and its metabolic products bind on two independent binding sites. Our findings support the existence of a reversible antioxidant redox cycle for BR and explain an additional pathway of the photo-isomerization process (increase of HSA binding capacity; the excess free [unbound] BR can be converted and also bound to HSA).
Department of Analytical Chemistry University of Chemistry and Technology Prague Czech Republic
Department of Physics and Measurements University of Chemistry and Technology Prague Czech Republic
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