The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the "yellow players-YP") are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.

• Klíčová slova
• Alzheimer’s disease, MAFLD, NRF2, Parkinson’s disease, bilirubin, cancer, heme-oxygenase, herbal medicine, neurodegeneration, nutraceuticals,
• MeSH
• bilirubin MeSH
• biliverdin MeSH
• dospělí MeSH
• hem MeSH
• hemová oxygenasa (decyklizující) MeSH
• játra MeSH
• lidé MeSH
• nemoci mozku * MeSH
• podpora zdraví * MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• bilirubin MeSH
• biliverdin MeSH
• hem MeSH
• hemová oxygenasa (decyklizující) MeSH

Human serum albumin (HSA) is the most abundant plasma protein in circulation. The three most important drug-binding sites on HSA are Sudlow's Site I (subdomain IIA), Sudlow's Site II (subdomain IIIA), and Heme site (subdomain IB). Heme site and Site I are allosterically coupled; therefore, their ligands may be able to allosterically modulate the binding affinity of each other. In this study, the effects of four Heme site ligands (bilirubin, biliverdin, hemin, and methyl orange) on the interaction of the Site I ligand warfarin with HSA were tested, employing fluorescence spectroscopic, ultrafiltration, and ultracentrifugation studies. Our major results/conclusions are the following. (1) Quenching studies indicated no relevant interaction, while the other fluorescent model used suggested that each Heme site ligand strongly decreases the albumin binding of warfarin. (2) Ultrafiltration and ultracentrifugation studies demonstrated the complex modulation of warfarin-HSA interaction by the different Heme site markers; for example, bilirubin strongly decreased while methyl orange considerably increased the bound fraction of warfarin. (3) Fluorescence spectroscopic studies showed misleading results in these diligand-albumin interactions. (4) Different Heme site ligands can increase or decrease the albumin binding of warfarin and the outcome can even be concentration dependent (e.g., biliverdin and hemin).

• Klíčová slova
• Sudlow’s site I, allosteric modulation, heme site, human serum albumin, warfarin,
• MeSH
• bilirubin MeSH
• biliverdin * MeSH
• hem metabolismus   MeSH
• hemin MeSH
• lidé MeSH
• ligandy MeSH
• sérový albumin metabolismus   MeSH
• warfarin * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bilirubin MeSH
• biliverdin * MeSH
• hem MeSH
• hemin MeSH
• ligandy MeSH
• methyl orange MeSH Prohlížeč
• sérový albumin MeSH
• warfarin * MeSH

Significance: As the central metabolic organ, the liver is exposed to a variety of potentially cytotoxic, proinflammatory, profibrotic, and carcinogenic stimuli. To protect the organism from these deleterious effects, the liver has evolved a number of defense systems, which include antioxidant substrates and enzymes, anti-inflammatory tools, enzymatic biotransformation systems, and metabolic pathways. Recent Advances: One of the pivotal systems that evolved during phylogenesis was the heme catabolic pathway. Comprising the important enzymes heme oxygenase and biliverdin reductase, this complex pathway has a number of key functions including enzymatic activities, but also cell signaling, and DNA transcription. It further generates two important bile pigments, biliverdin and bilirubin, as well as the gaseous molecule carbon monoxide. These heme degradation products have potent antioxidant, immunosuppressive, and cytoprotective effects. Recent data suggest that the pathway participates in the regulation of metabolic and hormonal processes implicated in the pathogenesis of hepatic and other diseases. Critical Issues: This review discusses the impact of the heme catabolic pathway on major liver diseases, with particular focus on the involvement of cellular targeting and signaling in the pathogenesis of these conditions. Future Directions: To utilize the biological consequences of the heme catabolic pathway, several unique therapeutic strategies have been developed. Research indicates that pharmaceutical, nutraceutical, and lifestyle modifications positively affect the pathway, delivering potentially long-term clinical benefits. However, further well-designed studies are needed to confirm the clinical benefits of these approaches. Antioxid. Redox Signal. 35, 734-752.

• Klíčová slova
• bilirubin, biliverdin, carbon monoxide, heme catabolic pathway, heme oxygenase, oxidative stress,
• MeSH
• biliverdin metabolismus   MeSH
• hem * metabolismus   MeSH
• hemová oxygenasa (decyklizující) metabolismus   MeSH
• hemoxygenasa-1 metabolismus   MeSH
• lidé MeSH
• nemoci jater * MeSH
• oxid uhelnatý metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biliverdin MeSH
• hem * MeSH
• hemová oxygenasa (decyklizující) MeSH
• hemoxygenasa-1 MeSH
• oxid uhelnatý MeSH

Pigment-based coloration is a common trait found in a variety of organisms across the tree of life. For example, calcareous avian eggs are natural structures that vary greatly in color, yet just a handful of tetrapyrrole pigment compounds are responsible for generating this myriad of colors. To fully understand the diversity and constraints shaping nature's palette, it is imperative to characterize the similarities and differences in the types of compounds involved in color production across diverse lineages. Pigment composition was investigated in eggshells of eleven paleognath bird taxa, covering several extinct and extant lineages, and shells of four extant species of mollusks. Birds and mollusks are two distantly related, calcareous shell-building groups, thus characterization of pigments in their calcareous structures would provide insights to whether similar compounds are found in different phyla (Chordata and Mollusca). An ethylenediaminetetraacetic acid (EDTA) extraction protocol was used to analyze the presence and concentration of biliverdin and protoporphyrin, two known and ubiquitous tetrapyrrole avian eggshell pigments, in all avian and molluscan samples. Biliverdin was solely detected in birds, including the colorful eggshells of four tinamou species. In contrast, protoporphyrin was detected in both the eggshells of several avian species and in the shells of all mollusks. These findings support previous hypotheses about the ubiquitous deposition of tetrapyrroles in the eggshells of various bird lineages and provide evidence for its presence also across distantly related animal taxa.

• MeSH
• barva * MeSH
• biliverdin analýza   MeSH
• biologické pigmenty analýza   MeSH
• hmotnostní spektrometrie MeSH
• měkkýši fyziologie   MeSH
• pigmentace MeSH
• protoporfyriny analýza   MeSH
• ptáci fyziologie   MeSH
• vaječná skořápka chemie   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• biliverdin MeSH
• biologické pigmenty MeSH
• protoporfyriny MeSH

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).

• 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 structural formula of biologically important chiral pigments bilirubin and biliverdin differs only by one double bond. We showed that this results in dissimilar interactions with two models of membranes: cationic liposomes composed of 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol and zwitterionic micelles from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). While the liposomes recognized the P-form of bilirubin, the micelles recognized its M-form. Both recognized the P-form of biliverdin. Our study also comprised ternary systems consisting of the pigments, model membranes and serum albumin (human and bovine). Bilirubin preferentially interacted with the albumins even in the presence of the liposomes. On the other hand, biliverdin preferred the liposomes. Remarkably, the presence of CHAPS completely changed the biliverdin binding to the protein. Because our study was oriented on different chiral interactions, a chiroptical method of electronic circular dichroism was chosen as the principal method to study our systems. As complementary methods, UV-vis absorption and fluorescence emission were used.

• Klíčová slova
• Bilirubin, Biliverdin, Electronic circular dichroism, Liposome, Micelle, Serum albumin,
• MeSH
• biliverdin chemie   metabolismus   MeSH
• cholesterol analogy a deriváty   metabolismus   MeSH
• kompetitivní vazba MeSH
• kyseliny cholové metabolismus   MeSH
• lidé MeSH
• micely * MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• sérový albumin hovězí metabolismus   MeSH
• skot MeSH
• stereoizomerie MeSH
• unilamelární lipozómy chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate MeSH Prohlížeč
• 3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol MeSH Prohlížeč
• biliverdin MeSH
• cholesterol MeSH
• kyseliny cholové MeSH
• micely * MeSH
• sérový albumin hovězí MeSH
• unilamelární lipozómy MeSH

Avian eggshells are variable in appearance, including coloration. Here, we demonstrate that Raman spectroscopy can provide accurate diagnostic information about major eggshell constituents, including the pigments biliverdin and protoporphyrin IX. Eggshells pigmented with biliverdin showed a series of pigment-diagnostic Raman peaks under 785 nm excitation. Eggshells pigmented with protoporphyrin IX showed strong emission under 1064 nm and 785 nm excitation, whereas resonance Raman spectra (351 nm excitation) showed a set of protoporphyrin IX informative peaks characteristic of protoporphyrin IX. As representative examples, we identified biliverdin in the olive green eggshells of elegant crested tinamous (Eudromia elegans) and in the blue eggshells of extinct upland moa (Megalapteryx didinus). This study encourages the wider use of Raman spectroscopy in pigment and coloration research and highlights the value of this technique for non-destructive analyses of museum eggshell specimens.

• Klíčová slova
• Biliverdin, Chemical analysis, Moa, Non-destructive, Protoporphyrin IX, Tinamou,
• MeSH
• barva MeSH
• biliverdin analýza   MeSH
• biologické pigmenty analýza   MeSH
• protoporfyriny analýza   MeSH
• ptáci * MeSH
• Ramanova spektroskopie MeSH
• vaječná skořápka chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biliverdin MeSH
• biologické pigmenty MeSH
• protoporfyriny MeSH
• protoporphyrin IX MeSH Prohlížeč

Complexation of bilirubin (BR) and biliverdin (BV) with biogenic and toxic metals (Mn, Cu, Cd, Co, Fe, Ni, Zn, and Ag) has been studied by means of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD). Poly-L-lysine and beta-cyclodextrin in water were chosen as matrices capable of recognizing the single stereoconformer of the pigments with defined M-helicity. Such systems allow structural changes caused by complexation of pigments with metals in aqueous solution at pH 10-11 to be followed using chiroptical methods, which are intrinsically sensitive to spatial structure. These and other spectroscopic techniques have revealed that BV and BR form monomeric complexes with Cd, Cu, and Zn and dimeric complexes with Mn. The stabilities of the complexes with Fe, Ni, Co, and Ag are remarkably lower. The sign of the ECD and VCD patterns of the complexed BV does not change for the chelates of any of the studied metals other than Zn, this exception being interpreted in terms of manifestation of the opposite helicity of BV in its chelate with Zn. In the case of BR, the observed inversion of ECD signal after complexation, together with the analysis of VCD spectra, reveals that a flattening of the molecule takes place, i.e., an increase in the angle between the pyrrinone chromophores without an inversion of helicity. This chiral stereoselectivity, which is very specific in the case of the Zn chelates, is discussed in connection with the specific inhibition of Zn-required enzymes by bile pigments.

• MeSH
• bilirubin analýza   chemie   MeSH
• biliverdin analýza   chemie   MeSH
• cirkulární dichroismus metody   MeSH
• elektrony MeSH
• molekulární struktura MeSH
• polylysin chemie   MeSH
• spektrofotometrie infračervená MeSH
• těžké kovy analýza   chemie   MeSH
• vibrace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bilirubin MeSH
• biliverdin MeSH
• polylysin MeSH
• těžké kovy MeSH

Stereoselective recognition of bilirubin and biliverdin by poly(L-lysine) (PLL), poly(D-lysine) (PDL), and poly(L-arginine) (PLA) and their micelles with dodecanoate ions (C(12)) at different pH has been studied using a combination of vibrational and electronic circular dichroism. Biliverdin has been found to be more sensitive to pH in its complexes with the polypeptides. In acidic media in the complexes with PLL-C(12) and PDL-C(12) the conformation becomes more closed than the characteristic one found at physiological pH. Partial flattening and chiral self-association of bilirubin molecules takes place at higher concentrations with PLL and PDL. For both pigments, inversions of the ECD signals are observed in the systems with PLA at pH > or = 8.5. This study was carried out in order to clarify the role of Lys and Arg residues in pigment binding to serum albumin. The circular dichroism spectra obtained for bilirubin bound to different mammalian serum albumins have been compared with the homology within the IIA principal ligand-binding structural domains. Analysis suggests that the chiroptical properties of the pigment in the complexes with serum albumins depend on the location of Lys and/or Arg at positions 222 and 199 in the binding site.

• MeSH
• albuminy chemie   metabolismus   MeSH
• biliverdin MeSH
• cirkulární dichroismus * MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• peptidy chemie   metabolismus   MeSH
• polylysin MeSH
• vazba proteinů MeSH
• žlučové pigmenty chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• albuminy MeSH
• biliverdin MeSH
• peptidy MeSH
• polyarginine MeSH Prohlížeč
• polylysin MeSH
• žlučové pigmenty MeSH

The study of bilirubin photochemical degradation in the presence of riboflavin has shown that, in this case, the primary process is photooxidation during which riboflavin acts as a receptor and bilirubin as a donor of electrons. The reaction proceeds under anaerobic conditions in an equilibrated manner, under aerobic ones as a catalytic process during which the catalyst, i. e., riboflavin is regenerated. The primary intermediate product is biliverdin in vitro, later this is further broken down. For the purpose of studying the mechanism of this process liquid chromatography and computerized technique based on solving nonlinear differential equations have been used. It appears that during phototherapy in the newborn infant there develops a decrease of the blood level of riboflavin reaching up to hypovitaminotic values and a transient biliverdin level elevation. Oral riboflavin administration may maintain this level within physiological range and at the same time shorten the necessary duration of phototherapy. In severe cases of hyperbilirubinaemia a shift of the ratio between flavin-adenin-dinucleotide and free riboflavin, as compared to the physiological state, has been recorded. The results of this work are discussed in the light of our current knowledge concerning the mechanisms of bilirubin breakdown during prototherapy.

• MeSH
• bilirubin krev   MeSH
• biliverdin krev   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecká žloutenka krev   terapie   MeSH
• riboflavin krev   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bilirubin MeSH
• biliverdin MeSH
• riboflavin MeSH