Structure and thermal interconversion of cyclobilirubin IX α

Onishi, Shoju; Miura, Iwao; Isobe, Kazuo; Itoh, Shinji; Ogino, Tadayoshi; Yokoyama, T.; Yamakawa, Takeshi

doi:10.1042/bj2180667

Cited by 42 publications

(37 citation statements)

References 15 publications

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“…However, it is not completely resolved from the 4Z,15E-isomer and in the chromatogram appears as a shoulder eluting slightly ahead of peak 2. Peak 3 is the structural isomer lumirubin (6), which has also been called photobilirubin I1 (15) and cyclobilirubin (16).…”

Section: Resultsmentioning

confidence: 99%

“…However, serial sampling at 15-20 min intervals for 180 min from 14 individual fetuses (91-139 days) showed that TSH was secreted in a markedly exaggerated pulsatile manner compared to that observed after birth. The mean amplitude of TSH pulses fell (p < 0.005) from 5.9 2 8.1 pU/ml in the fetuses to 2.1 + 1.1 pU/ml in five neonatal lambs (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) days) and to 1.5 f 0.4 pU/ml in three adult nonpregnant ewes. The mean pulse frequency for the 14 fetuses was 0.7 + 0.3 pulses/h and was reduced (p < 0.001) to 0.3 + 0.1 pulseslh in lambs and to 0.3 f 0.1 pulses/h in the ewes.…”

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confidence: 99%

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Phototherapy for Neonatal Jaundice: in Vivo Clearance of Bilirubin Photoproducts

et al. 1985

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ABSTRACT. Phototherapy results in the conversion of native bilirubin to more water-soluble configurational and structural isomers. The serum half-life for the configurational isomer, the principal photoproduct in vivo, was determined by high pressure liquid chromatography in six premature infants following cessation of phototherapy. The mean half-life for this isomer was 15 h. The excretion of this isomer, calculated from the measured half-life, is less than half of daily bilirubin production, and therefore cannot account for the total bilirubin elimination observed during phototherapy. The serum concentration of the structural isomer, lumirubin, is lower than that of the configurational isomer; however, excretion is more rapid (serum half-life < 2 h). Because of its rapid excretion, lumirubin may be an important pathway for bilirubin elimination during phototherapy. (Pediatr Res 19: 205-208, 1985) Abbreviation HPLC, high pressure liquid chromatography Despite the widespread use of phototherapy in the treatment of neonatal hyperbilirubinemia (l), the detailed mechanism by which visible light affects bilirubin metabolism in jaundiced newborns is not known. The purpose of this study was to measure the rate of elimination of the principal bilirubin photoproduct, 4Z,15E-bilirubin, and to determine whether this is sufficient to Received June 22, 1984; accepted October 3, 1984. Address account for the decline in plasma bilirubin observed during phototherapy.Bilirubin, derived from the degradation of heme, is a potentially toxic, highly lipophylic molecule. In mammals this pigment is ravidlv cleared from the circulation and excreted as a ducuronide~onju~ate, primarily in the bile (2). Newborn i n f a k commonly develop hyperbilirubinemia due in part to a decreased ability to conjugate bilirubin and an increased pigment load. During vhototheravy, the most commonlv used treatment for unconj~~ated&~~dilirubinemia, bilirubin undergoes several reactions (3-7). All of these reactions yield photoproducts which are more polar and therefore presumably more easily excreted than native bilirubin. The fastest photochemical reaction is a Z to E isomerization reaction (5, 8) which in human infants yields primarily the 4Z,15E-bilirubin isomer (6). This reaction is readily reversible and up to 20% of the total bilirubin can be converted to this isomer during phototherapy (9-12).Since the quantum yield of the configurational isomerization reaction is at least 40 times greater than that for any other photochemical reaction of bilirubin (8), it has been assumed that the elimination of bilirubin during phototherapy is the result of formation and excretion of this photoproduct. We have used a rapid, quantitative HPLC method (5) to measure the half-life of the configurational isomer in serum of preterm infants undergoing phototherapy. We have found that the rate of elimination of the 4Z,15E-bilirubin isomer is much slower than previously reported (13) and cannot account for the decline in serum bilirubin observed in infants treated wit...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Phototherapy for Neonatal Jaundice: in Vivo Clearance of Bilirubin Photoproducts

et al. 1985

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“…The second isosbestic point results from the formation of a second photoproduct, previously identified as "lumirubins" (12), also referred to as "cyclobilirubin" (9), "unknown pigment" (1 l), and "pigment 430" (21), that has an absorbance maximum around 430nm (10). Lumirubin is a configurational isomer of bilirubin formed by an endo-vinyl cyclization on one end ring of the molecule (11,13,22).…”

Section: Results and Discussion ( A ) Photolysis In Pure Chloroformmentioning

confidence: 99%

“…Further work showed that there are in fact a number of photoproducts, including both structural and geometric isomers (10)(11)(12)(13). Furthermore, the photoproduct formed, and in what proportion, seems to be a function of many parameters, including the nature of the solvent and the presence or absence of oxygen or of proteins such as albumin.…”

Section: Introductionmentioning

confidence: 99%

Solvent effects on the photoisomerization of bilirubin

Sailofsky¹,

Brown²

1987

Can. J. Chem.

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. J. Chem. 65, 1908 (1987).Studies of the photolysis of bilirubin IX-a by absorbance difference (AD) spectroscopy show that in solvents which do not interfere with the intramolecular hydrogen bonding, e.g., CHCI3, EZIZE isomers and lumirubins are formed, with the former being predominant. The addition of ethanol to CHC13, either before or during photolysis, greatly changes the AD spectra, possibly because of a reaction of photoproducts with the ethanol or solvatochromism of the EZIZE isomers. Solvents which interfere with the intramolecular hydrogen bonding of bilirubin, e.g., DMSO, increase the importance of the photoreaction that forms lumirubins. The kinetics of product formation indicate that the lumirubins result from a photoreaction of EZIZE isomers. The addition of aqueous buffer to DMSO lowers the extent of photoisomerization and leads to AD spectra that resemble those obtained for the photolysis in CHCI3. The addition of human serum albumin (HSA), using stopped flow techniques, to aqueous buffer solution of bilirubin immediately after photolysis gives evidence that the HSA traps the EZIZE isomers and prevents their reversion. However, in the presence of HSA the predominant pathway for photoreaction of bilirubin to EZIZE isomers is by reaction of the bound bilirubin. The AD spectra are similar to those obtained for solvents that interfere with hydrogen bonding. B. M. SAILOFSKY et G. R. BROWN. Can. J. Chem. 65, 1908 (1987).Les Ctudes de spectroscopie par absorbance differentielle (AD) ont dkmontrC que la photolyse de la bilirubine-IXa poursuivie en milieux qui ne perturbent pas les liaisons hydrogttnes, tel que le chloroforme, produit principalement les isomkres EZIZE, ainsi que des lumirubines. L'addition d'ithanol, par exemple au chloroforme, soit avant ou aprks la photolyse transforme les spectres AD, peut-&tre a la suite d'une rCaction des photoproduits avec 1'Cthanol ou en raison du solvatochromisme des isomttres EZIZE. Par contre, la formation des lumirubines par photorCaction est favoriskc dans des solvants tel que le sulphoxyde dimCthylique, c'est-a-dire dans des solvants qui perturbent les liaisons hydrogttnes. Ainsi, les rksultats d'Ctudes de cinktique dCmontrent que les lumirubines sont formCes par la photortaction des isomttres EZIZE. L'addition de solutions tampons aqueuses au sulphoxyde dimkthylique diminue le degrk de photoisomCrisation et les spectres AD obtenus ressemblent a ceux obtenus aprtts la photolyse dans le chloroforme. L'addition de la skrum-albumine humaine (SAH), immkdiatement aprts la photolyse, a des solutions tampons aqueuses de bilirubine en utilisant des techniques d'additions simultankes, indique que la SAH capte les isomttres EZIZE et emp&che leur inversion. Cependant, la photorCduction de la bilirubine en isomttres EZIZE en prCsence de la SAH se poursuit principalement par rkaction des bilirubines likes. Les spectres AD obtenus sont semblables ii ceux obtenus dans des milieux cjui perturbent les liaisons hydrogttnes.

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“…The discoloration of skin is mainly explained by the accumulation of photoisomers and pigments derived from bilirubin which are not excreted in bile and urine [1,2]. It has been confirmed that phototherapy causes the phototransition of free bilirubin to more polar photoisomers such as bilirubin IXαE [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%