- Effect of Serum Albumins from Several Mammals on the Photoisomerization of Bilirubin
-
ZZ-Bilirubin undergoes photoisomerization to configurational (ZE and EZ isomers) and structural (LR) isomers in buffered aqueous solution containing serum albumins.The efficiency and the course of the isomerization are very much dependent on the mammals from which serum albumins are taken.
- Kanna, Yoko,Arai, Tatsuo,Tokumaru, Katsumi
-
-
Read Online
- Bilirubin photo-isomers: Regiospecific acyl glucuronidation in vivo
-
(4Z,15Z)-Bilirubin-IXα, the end product of heme catabolism, requires uridine glucuronosyl transferase 1A1 (UGT1A1)-catalyzed glucuronidation for elimination in bile, where it appears as two isomeric monoglucuronides and a diglucuronide. When people are exposed to light, endogenous bilirubin is converted partly to photo-isomers that are produced in greater abundance during treatment of jaundiced babies with phototherapy. Little is known about the metabolism of the photo-isomers, other than that they appear not to require glucuronidation for elimination in bile. Studies have been hampered by their unavailability and instability, as well as confusion about the identity, structures, preparation, and purity of bilirubin photoproducts. This paper outlines methods for preparing photo-isomers of bilirubins in sufficient quantity and purity for metabolic studies in rats and reappraises the composition of some previous preparations. The studies show that (Z,E)-isomers of bilirubins and the structural isomer (Z)-lumirubin undergo glucuronidation in the rat, but unlike (4Z,15Z)-bilirubin, form only monoglucuronides. Moreover, glucuronidation is regiospecific for just one of the two propionic acid groups, the one attached to the isomerized half of the molecule. This unusual stereoselectivity appears to be dictated by intramolecular hydrogen bonding. Formation of hydroxylated bilirubins was not detected. During phototherapy, photo-isomers will compete with endogenous (4Z,15Z)-bilirubin for glucuronidation by nascent hepatic enzyme UGT1A1. Graphical abstract: [Figure not available: see fulltext.]
- McDonagh, Antony F.
-
-
Read Online
- A method for preparing high-content bilirubin IX[alpha] from bilirubin IX[alpha] diester
-
A method for preparing high-content bilirubin IX[alpha] from bilirubin IX[alpha] diester is disclosed, belonging to the field of bilirubin IX[alpha] preparation. The method includes following steps (aroute including firstly hydrolysis and then reduction): a step of adding dropwise a methanol solution of sodium hydroxide into an alcohol solution of bilirubin IX[alpha] diester, adding water, then performing hydrolysis, adjusting pH to 4-5 with a weak acid, performing rotary evaporation to remove a solvent, washing a product with water to remove inorganic salt, and performing vacuum drying to obtain bilirubin IX[alpha]; and a step of adding a free radical scavenger (stabilizer) into an alcohol solution of the bilirubin IX[alpha], adding a reductant that is borohydride, adding an acetone immediately after reduction is finished to decompose the excessive reductant, then adjusting pH to 4-5 with weak acid, performing rotary evaporation to remove a solvent, performing water washing, and performing purification with methanol and chloroform to obtain bilirubin IX[alpha] the purity of which is more than 97%. The method has characteristics of no need of chromatographic separation, mild reaction conditions, low cost, and convenient operation, and is suitable for industrial large-scale production.
- -
-
Paragraph 0028; 0041-0043; 0050-0055
(2019/04/10)
-
- PRODUCTION OF RED BLOOD CELLS AND PLATELETS FROM STEM CELLS
-
This disclosure provides methods of making a megakaryocyte-erythroid progenitor cell (MEP), comprising differentiating a stem cell into a MEP in culture in the presence of an aryl hydrocarbon receptor (AhR) agonist. In some embodiments the stem cell is a pluripotent stem cell. In some embodiments the MEP co-expresses CD41 and CD235. In some embodiments the number of MEPs produced in the culture increases exponentially. Methods of making a red blood cell (RBC) by culturing a MEP in the presence of an AhR agonist are also provided. Methods of making a megakaryocyte and/or a platelet, comprising culturing a MEP in the presence of an AhR modulator are also provided. In some embodiments the AhR modulator is an AhR antagonist. This disclosure also provides compositions comprising at least 1 million MEPs per ml and compositions in which at least 50% of the cells are MEPs.
- -
-
-
- Induction of wavelength-dependent photochemistry in bilirubins by serum albumin
-
Quantum yields for Z ? E photoisomerization of the natural bi-chromophore bilirubin IXα in ammoniacal methanol solution were found to vary with excitation wavelength, whereas no variation (within experimental error) was observed for xanthobilirubic acid and for symmetrically substituted bilirubins (bilirubin IIIα, bilirubin XIIIα, and mesobilirubin XIIα) in the same solvent. The quantum yield for Z ? E photoisomerization of xanthobilirubic acid bound to human serum albumin was also invariant with excitation wavelength. In contrast, quantum yields for Z ? E photoisomerization of the symmetrically-substituted bilirubins did show marked excitation wavelength dependency when they were bound to human serum albumin. These results show that quantum yields for Z ? E photoisomerization of bilirubins are markedly sensitive to protein binding and to the nature of pyrrole ring β-substituents. They also demonstrate that wavelength-dependent photochemistry is characteristic of bilirubins with non-identical pyrromethenone chromophores, as expected from exciton coupling theory, and that complexation with albumin induces wavelength-dependent photochemistry in symmetrically substituted bilirubins.
- McDonagh, Antony F.,Agati, Giovanni,Lightner, David A.
-
p. 649 - 660
(2007/10/03)
-
- Effect of the Binding Sites of Human Serum Albumin on the Efficiency and Photostationary State Isomer Ratios of the Photoisomerization of Bilirubin
-
The quantum yields of the isomerization and photostationary state isomer ratios of the photoisomerization of (4Z,15Z)-bilirubin IXα (ZZ-BR) were determined in an aqueous buffered solution in the presence of human serum albumin (HSA) at a molar ratio of / from 0.5 to 2.The BR isomer compositions in the photostationary state were constant at /=0.5-0.7.With increasing / from 0.8 to 2, the ZZ-BR composition in the photostationary state increased from 58 to 75percent, but the ZE-BR composition decreased from 39 to 22percent.The quantum yields in the isomerization of ZZ-BR to ZE-BR (ΦZZ->ZE) and a cyclized product, lumirubin (LR), (ΦZZ->LR), remained unvaried up to /=1, but ΦZZ->ZE decreased while ΦZZ->LR increased along with a further increase of /.These results are explained by the existence of two binding sites, a first-class site and a second-class site, for bilirubin binding to HSA; ΦZZ->ZE in the second-class site (=0.035) was as low as 1/3 of that in the first-class site (=0.11), but ΦZZ->LR in the second-class site (=4.2*10-3) was nearly two-times higher than that in the first-class site (=2.4*10-3).
- Kanna, Yoko,Arai, Tatsuo,Tokumaru, Katsumi
-
p. 2758 - 2762
(2007/10/02)
-
- The synthesis of [10-13C]bilirubin IXα
-
The total synthesis of [10-13C]bilirubin IXα, the principal waste product of haem degradation, is described. Site specific labelling was accomplished by the Vilsmeier formylation of one of the dipyrrolic fragments using [1-13C]dimethylformamide. The penultimate dehydrohalogenation reaction was complicated by a competing elimination reaction which yielded a bridged biliverdin derivative. [10-13C]bilirubin IXα was prepared in an overall yield of 6% (from the step where 13C was introduced) with quantitative isotopic incorporation.
- Sturrock,Bull,Kirsch
-
p. 263 - 274
(2007/10/02)
-
- Photoisomerization of Bilirubins and the Role of Intramolecular Hydrogen Bonds
-
The quantum yields and the photostationary state isomer in the photoisomerization of bilirubin are strongly governed by the properties of the reaction media.Among the reaction media examined, the quantum yields for ZZ->ZE isomerization (φZZ-ZE) and for cyclization (φLR) were the highest in buffered aqueous solution (potassium phosphate buffer, pH 7.4) containing human serum albumin (HSA) in a 1:1 molar ratio to ZZ-BR, 0.11 and 2*10-3, respectively, on 436 nm irradiation.The effects of the reaction media surrounding bilirubin are discussed.
- Kanna, Yoko,Arai, Tatsuo,Tokumaru, Katsumi
-
p. 1482 - 1489
(2007/10/02)
-
- Effects of Solvents and Media on the Efficiency and Course of Photoisomerization of Bilirubins
-
The quantum yields of photoisomerization of bilirubin to various isomers were determined in various solvents.A specific photoisomerization took place only in buffered solutions containing human serum albumin.We discuss the effects of solvents and media surrounding bilirubin on its photoisomerization.
- Kanna, Yoko,Arai, Tatsuo,Sakuragi, Hirochika,Tokumaru, Katsumi
-
p. 631 - 634
(2007/10/02)
-
- Facile preparation of symmetric bilirubins IIIα and XIIIα from IXα
-
Improved, simple precedures for synthesis and isolation of symmetrically substituted bilirubin-XIIIα and bilirubin-IIIα from the natural pigment, bilirubin-IXα, are described.
- Ma,Lightner
-
p. 1005 - 1008
(2007/10/02)
-
- The Structure of "Photobilirubin"
-
Anaerobic irradiation of bilirubin in the region of the main absorption band produces the diastereomers of (Z,E)- and (E,Z)-configurations with high quantum yield.The structure of these "photobilirubins" is proven by a chemical correlation with the corresponding diastereomers of biliverdindimethylester characterised before.Their 1H-NMR spectroscopic features have been recorded and are discussed. - Keywords: (Z,Z)-, (Z,E)- and (E,Z)-Bilirubin; Photobilirubin; Neonatal jaundice; Phototherapy
- Falk, Heinz,Mueller, Norbert,Ratzenhofer, Michael,Winsauer, Karl
-
p. 1421 - 1432
(2007/10/02)
-
- BILIRUBIN CHEMISTRY. I. A SIMPLE METHOD FOR PROTECTING THE EXO-VINYL GROUP
-
Regiospecific addition of thioacetic acid followed by RHg(+)-induced methanolysis and acid-catalysed methanol elimination proves to be an efficient method for protecting the exo-vinyl group of bilirubin.An analogous mercury(II)-activated displacement on bilirubin-thioacetic acid addition product was used to obtain the hydroxybilirubin 3b of potential biological interest.The synthesis of "mercury-bilirubin" is also reported.
- Monti, Diego,Speranza, Giovanna,Manitto, Paolo
-
p. 361 - 366
(2007/10/02)
-