Jaundice pp 1-17 | Cite as

An Overview of Bilirubin Chemistry

  • Antony F. McDonagh
Part of the Hepatology book series (H, volume 2)


“From gall disease, that is from the yellow jaundice cometh great evil; it is of all disease most powerful, when there wax within a man, unmeasured humors; these are the tokens; that the patient’s body all becometh bitter and as yellow as good silk; and under the root of his tongue there be swart veins and pernicious, and his urine is yellow”(1). The yellow pigment referred to in this vivid eleventh-century Anglo-Saxon description of cirrhosis was first isolated in crystalline form by Virchow in 1847(2), and named bilirubin by Stadeler in 1864(3). Its structure was determined by Siedel and Fischer in 1933(4) and confirmed by total synthesis by Fischer and Plieninger in 1943(5) and more recently by Plieninger et al(6). Much of the basic chemistry of the pigment was elucidated more than two decades ago, principally by the Fischer school. And today, despite the fact that bilirubin is a metabolic waste-product of no practical utility other than its diagnostic value, scientific interest in the pigment continues unabated. In the past two to three years alone bilirubin has been mentioned in over 1600 publications, and of these about 400 specifically with some aspect of the chemistry or biochemistry of the molecule. The areas of bilirubin chemistry and biochemistry which appear to have received the most attention in recent years are the mechanism of bilirubin formation, the mechanism of bilirubin conjugation and excretion, the nature of bilirubin conjugates, bilirubin-protein complexes, and the photochemistry of bilirubin.


Singlet Oxygen Dimethyl Ester Toluene Sulfonic Acid Bilirubin Conjugate Sodium Amalgam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    COCKAYNE TO: Leechdoms, Wartcunning and Starcraft of Early England, The Holland Press, 1961, v II, P 107Google Scholar
  2. 2.
    VIRCHOW R: Die pathologischen pigmente. Arch Pathol Anat Physiol Klin Med 1 379–486, 1847Google Scholar
  3. 3.
    STADELER G: Ueber die Farbstoffe der Galle. Justus Liebigs Ann Chem 132: 323–354, 1864CrossRefGoogle Scholar
  4. 4.
    SIEDEL W, FISCHER H: Uber die Konstitution des Bilirubins, Synthesen der neo-und der iso-neoxanthobilirubinsaure. Hoppe Seylers Z Physiol Chem. 214: 145–172, 1933CrossRefGoogle Scholar
  5. 5.
    FISCHER H, PLIENINGER H: Synthese des Biliverdins (Uteroverdins) und Bilirubins, der Biliverdine XIIIα und IIIα, sowie der Vinyl-neoxanthosaure. Hoppe Seylers Z Physiol Chem. 274: 231–260, 1942CrossRefGoogle Scholar
  6. 6.
    PLIENINGER H, EL-BARKAWI F, EHL K, et al: Neue Synthese und c14C-Markierung von Bilirubin IX-α. Justus Liebigs Ann Chem 758: 195–201, 1972PubMedCrossRefGoogle Scholar
  7. 7.
    MCDONAGH AF, ASSISI F: Commercial bilirubin: A trinity of isomers. FEBS Lett 18: 315–317, 1971PubMedCrossRefGoogle Scholar
  8. 8.
    NEWBOLD BT, LEBLANC G: Physical properties of commercial bilirubins. Can J Biochem 42: 1697–1702, 1964PubMedCrossRefGoogle Scholar
  9. 9.
    FOG J: Bilirubin -purification -purity. Scand J Clin Lab Invest 16: 49–54, 1964PubMedCrossRefGoogle Scholar
  10. 10.
    MCDONAGH AF, ASSISI F: The ready isomerization of bilirubin IX-α in aqueous solution. Biochem J 129: 797–800, 1972PubMedGoogle Scholar
  11. 11.
    OVERBEEK JTG, VINK CLJ, DEENSTRA H: The solubility of bilirubin. Rec Trav Chim 74: 81–84, 1955CrossRefGoogle Scholar
  12. 12.
    BURNSTINE RC, SCHMID R: Solubility of bilirubin in aqueous solutions. Proc So. Exp Biol Med 109: 356–358, 1962Google Scholar
  13. 13.
    FOG J, BUGGE-ASPERHEIM B: Stability of bilirubin. Nature (Lond) 203: 756–757, 1964CrossRefGoogle Scholar
  14. 14.
    JIRSA M, SPONAR J: Das absorptionsspektrum, der physikalische zustand und die geschwindigkeit der diazoreaktion des bilirubins. Zeit gesamte Inn Med 11: 519–522, 1956Google Scholar
  15. MCDONAGH AF, PALMA LA: Unpublished observationsGoogle Scholar
  16. 16.
    HUTCHINSON DW, JOHNSON B, KNELL AJ: The synthesis of esters of bilirubin. Biochem J. 133: 493–498, 1973PubMedGoogle Scholar
  17. 17.
    KUENZLE CC, WEIBEL MH, PELLONI RR: The reaction of bilirubin with diazomethane. Biochem J 133: 357–368, 1973PubMedGoogle Scholar
  18. 18.
    FOG J, JELLUM E: Structure of bilirubin. Nature (Lond) 198: 88–89, 1963CrossRefGoogle Scholar
  19. 19.
    .PETRYKA Z: Variations in hydrogenation of bile pigments depending upon type of solvent and other factors. Ann NY Acad Sci 206: 701–710, 1973PubMedCrossRefGoogle Scholar
  20. 20.
    RUDIGER W: Gallenfarbstoffe und Biliproteide. Fortschr Chem Org Naturst 29: 60–139, 1971PubMedGoogle Scholar
  21. 21.
    NICHOL AW, MORELL DB: Tautomerism and hydrogen bonding in bilirubin and biliverdin. Biochim Biophys Acta 177: 599–609, 1969PubMedCrossRefGoogle Scholar
  22. 22.
    BONNETT R, MCDONAGH AF: The isomeric heterogeneity of biliverdin dimethyl ester derived from bilirubin. J Chem Soc D (Chem Common): 238–239, 1970Google Scholar
  23. 23.
    BINGOLD K: Weitere Untersuchunger zur Formulierung eines biologisch-chemischen Blutkreislaufes. Klin Wochenshr14: 1287–1289, 1935CrossRefGoogle Scholar
  24. 24.
    OSTROW JD, HAMMAKER L, SCHMID R: The preparation of crystalline bilirubin-C14. J Clin Invest. 40: 1442–1452, 1961PubMedCrossRefGoogle Scholar
  25. 25.
    WITH TK: Bile: Pigments. New York, Academic Press, 1968, p 25Google Scholar
  26. 26.
    MCDONAGH AF: The role of singlet oxygen in bilirubin photo-oxidation. Biochem Biophys Res. Commun 44: 1306–1311, 1971PubMedCrossRefGoogle Scholar
  27. 27.
    BONNETT R, STEWART JCM: Singlet oxygen in the photo-oxidation of bilirubin in hydroxylic solvents. Biochem J 130: 895–897, 1972PubMedGoogle Scholar
  28. 28.
    LIGHTNER DA, QUISTAD GB: Imide products from photo-oxidation of bilirubin and mesobilirubin. Nature (New Biol) 236: 203–205, 1972.Google Scholar
  29. 29.
    LIGHTNER DA, QUISTAD GB: Hematinic acid and propentdyopents from bilirubin photo-oxidation in vitro. FEBS Lett 25: 94–96, 1972PubMedCrossRefGoogle Scholar
  30. 30.
    BONNETT R: Recent advances in tetrapyrrole chemistry. Ann NY Acad Sci 206: 722–733, 1973PubMedCrossRefGoogle Scholar
  31. 31.
    BONNETT R, STEWART JCM: Photo-oxidation of bilirubin in hydroxylic solvents: propentdyopent adducts as major products. J Chem Soc Chem Commun: 596–597, 1972Google Scholar
  32. BONNETT R, STEWART, JCM: Personal communication.Google Scholar
  33. 33.
    MCDONAGH AF: Evidence for singlet oxygen quenching by biliverdin IX-α dimethyl ester and its relevance to bilirubin photo-oxidation. Biochem Biophys Res Commun48: 408–415, 1972PubMedCrossRefGoogle Scholar
  34. 34.
    LIGHTNER DA, CRANDALL DC, GERTLER S, et al: On the formation of biliverdin during photooxygenation of bilirubin in vitro. FEBS Lett 30: 309–312, 1973PubMedCrossRefGoogle Scholar
  35. MCDONAGH AF: Phototherapy of neonatal jaundice: photochemistry and photometabolism of bilirubin, in Phototherapy: An Overview, Washington, National Academy of Sciences, In PressGoogle Scholar
  36. MCDONAGH AF: Thermal and photochemical reactions of bilirubin IX-α. Ann NY Acad Sci: In pressGoogle Scholar
  37. 37.
    MANITTO P, MONTI D: Acid-catalyzed addition of alcohols and thiols to bilirubin. Experientia 29: 137–139, 1973PubMedCrossRefGoogle Scholar
  38. 38.
    MANITTO P: Photochemistry of bilirubin. Experientia 27: 1147–1149, 1971PubMedCrossRefGoogle Scholar
  39. 39.
    MANITTO P, MONTI D: Photoaddition of sulphydryl groups to bilirubin in vitro. Experientia 28: 379–380, 1972.PubMedCrossRefGoogle Scholar
  40. 40.
    GARBAGNATI E, MANITTO P: A new class of bilirubin photo-derivatives obtained in vitro and their possible formation in jaundiced infants. J Pediatr 83: 109–115, 1973PubMedCrossRefGoogle Scholar
  41. 41.
    MCDONAGH AF, ASSISI F: Direct evidence for the acid-catalyzed isomeric scrambling of bilirubin IX-α. J Chem Soc Chem Commun: 117–119, 1972Google Scholar
  42. 42.
    HUTCHINSON DW, JOHNSON B, KNELL AJ: The reaction between bilirubin and aromatic diazo compounds. Biochem J 127: 907–908, 1972PubMedGoogle Scholar
  43. 43.
    JANSEN PLM: The isomerisation of bilirubin monoglucuronide. Clin Chim Acta 49: 233–240, 1973PubMedCrossRefGoogle Scholar
  44. 44.
    OSTROW JD: Photocatabolism of labeled bilirubin in the congenitally jaundiced (Gunn) rat. J Clin Invest 50: 707–718, 1971PubMedCrossRefGoogle Scholar
  45. 45.
    DIAMOND I: Bilirubin binding and kernicterus. Adv Pediatr 16: 99–119, 1969PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Antony F. McDonagh
    • 1
  1. 1.University of California, San FranciscoSan FranciscoUSA

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