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Chemical Compound Review

AC1O5FOR     3-[2-[[3-(2-carboxyethyl)-5- [(Z)-(3...

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Disease relevance of bilirubin


Psychiatry related information on bilirubin


High impact information on bilirubin

  • The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO) [11].
  • In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile [12].
  • Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks [12].
  • These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs [12].
  • Reduced expression of bilirubin UDP-glucuronosyltransferase 1 due to an abnormality in the promoter region of the gene for this enzyme appears to be necessary for Gilbert's syndrome but not sufficient for the complete manifestation of the syndrome [13].

Chemical compound and disease context of bilirubin


Biological context of bilirubin


Anatomical context of bilirubin

  • Although several studies suggested that it is the small, unbound fraction of bilirubin which interacts with hepatocytes and is removed from the circulation, recent experiments have been interpreted as suggesting that binding to albumin facilitates ligand uptake [24].
  • Infusions of heme, which is taken up primarily in hepatocytes, or of heat-damaged erythrocytes, which are taken up in reticuloendothelial cells, resulted in marked increases in bilirubin output in bile in control animals; these increases were completely prevented or substantially diminished by Sn-protoporphyrin administration [25].
  • Bile duct ligation in the rat and guinea pig led to rapid accumulation in the circulation of bilirubin, heterogeneous bilirubin esters of glucuronic acid, and a biliprotein that migrated along with albumin on high performance liquid chromatography [26].
  • Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin [27].
  • A rabbit antibody to the BSP-binding protein gave a line of identity with both the BSP- and bilirubin-binding antigens, and inhibited the binding of [14C]bilirubin and [35S]BSP, but not [14C]oleate or [14C]taurocholate, to rat liver plasma membranes [28].

Associations of bilirubin with other chemical compounds

  • Prednisolone decreased serum bilirubin (P < 0.05) and globulin (P < 0.01) at three months; it delayed other biochemical remission occurring after the second month of medication (P < 0.001); it hastened biochemical relapse (P < 0.0001); and it increased the frequency of complications (P < 0.0001) and the death rate (P < 0.01) [29].
  • Heme oxygenase ((HO); EC is the rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO) [30].
  • To examine the hypothesis that glutathione S-transferases (GST) play an important role in the hepatocellular transport of hydrophobic organic anions, the kinetics of the spontaneous transfer of unconjugated bilirubin between membrane vesicles and rat liver glutathione S-transferase B (ligandin) was studied, using stopped-flow fluorometry [23].
  • Uridine diphosphate-glucuronic acid-independent conversion of bilirubin monoglucuronides to diglucuronide in presence of plasma membranes from rat liver is nonenzymic [31].
  • Physicochemical and immunohistological studies of a sulfobromophthalein- and bilirubin-binding protein from rat liver plasma membranes [28].

Gene context of bilirubin


Analytical, diagnostic and therapeutic context of bilirubin

  • The 3 men in the control group who were homozygous for the longer TATAA element had significantly higher serum bilirubin levels than the other 52 normal subjects (P = 0.009) [13].
  • Survival for at least one year was associated with a patient's being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 mumol per liter), and having a complete response [37].
  • This is consistent with geometric isomerization of bilirubin IXalpha as a primary step in phototherapy [38].
  • In the present study, a cholestatic animal model was used to determine the chemical nature of the bilirubin species involved in its formation [39].
  • The major bile pigments in the matrix were identified as bilirubin (84%) and bilirubin monoglucuronide (15%) by thin-layer chromatography [40].


  1. The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. Weiss, J.S., Gautam, A., Lauff, J.J., Sundberg, M.W., Jatlow, P., Boyer, J.L., Seligson, D. N. Engl. J. Med. (1983) [Pubmed]
  2. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. Vento, S., Garofano, T., Renzini, C., Cainelli, F., Casali, F., Ghironzi, G., Ferraro, T., Concia, E. N. Engl. J. Med. (1998) [Pubmed]
  3. Ultrasonographic fetal surveillance in the management of the isoimmunized pregnancy. Frigoletto, F.D., Greene, M.F., Benacerraf, B.R., Barss, V.A., Saltzman, D.H. N. Engl. J. Med. (1986) [Pubmed]
  4. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. Poupon, R.E., Balkau, B., Eschwège, E., Poupon, R. N. Engl. J. Med. (1991) [Pubmed]
  5. Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. Poupon, R.E., Poupon, R., Balkau, B. N. Engl. J. Med. (1994) [Pubmed]
  6. Fasting-related hyperbilirubinemia in rats: the effect of decreased intestinal motility. Kotal, P., Vítek, L., Fevery, J. Gastroenterology (1996) [Pubmed]
  7. A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered metabolism. Atamna, H., Frey, W.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Increased signals seen in globus pallidus in T1-weighted magnetic resonance imaging in cirrhotics are not suggestive of chronic hepatic encephalopathy. Thuluvath, P.J., Edwin, D., Yue, N.C., deVilliers, C., Hochman, S., Klein, A. Hepatology (1995) [Pubmed]
  9. Optimized microturbidimetric assay for fibrinogen. Macart, M., Koffi, A., Henocque, G., Mathieu, J.F., Guilbaud, J.C. Clin. Chem. (1989) [Pubmed]
  10. Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study. Bathum, L., Petersen, H.C., Rosholm, J.U., Hyltoft Petersen, P., Vaupel, J., Christensen, K. Clin. Chem. (2001) [Pubmed]
  11. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Ryter, S.W., Alam, J., Choi, A.M. Physiol. Rev. (2006) [Pubmed]
  12. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Kikuchi, S., Hata, M., Fukumoto, K., Yamane, Y., Matsui, T., Tamura, A., Yonemura, S., Yamagishi, H., Keppler, D., Tsukita, S., Tsukita, S. Nat. Genet. (2002) [Pubmed]
  13. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. Bosma, P.J., Chowdhury, J.R., Bakker, C., Gantla, S., de Boer, A., Oostra, B.A., Lindhout, D., Tytgat, G.N., Jansen, P.L., Oude Elferink, R.P. N. Engl. J. Med. (1995) [Pubmed]
  14. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. Rosenberg, S.A., Lotze, M.T., Muul, L.M., Chang, A.E., Avis, F.P., Leitman, S., Linehan, W.M., Robertson, C.N., Lee, R.E., Rubin, J.T. N. Engl. J. Med. (1987) [Pubmed]
  15. Structure of the murine constitutive androstane receptor complexed to androstenol: a molecular basis for inverse agonism. Shan, L., Vincent, J., Brunzelle, J.S., Dussault, I., Lin, M., Ianculescu, I., Sherman, M.A., Forman, B.M., Fernandez, E.J. Mol. Cell (2004) [Pubmed]
  16. Serum albumin, bilirubin, and uric acid and the anatomic site-specific incidence of colon cancer. Ko, W.F., Helzlsouer, K.J., Comstock, G.W. J. Natl. Cancer Inst. (1994) [Pubmed]
  17. Two distinct mechanisms for bilirubin glucuronide transport by rat bile canalicular membrane vesicles. Demonstration of defective ATP-dependent transport in rats (TR-) with inherited conjugated hyperbilirubinemia. Nishida, T., Gatmaitan, Z., Roy-Chowdhry, J., Arias, I.M. J. Clin. Invest. (1992) [Pubmed]
  18. Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I. van Es, H.H., Goldhoorn, B.G., Paul-Abrahamse, M., Elferink, R.P., Jansen, P.L. J. Clin. Invest. (1990) [Pubmed]
  19. Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. Ellis, C.N., Fradin, M.S., Messana, J.M., Brown, M.D., Siegel, M.T., Hartley, A.H., Rocher, L.L., Wheeler, S., Hamilton, T.A., Parish, T.G. N. Engl. J. Med. (1991) [Pubmed]
  20. Bilirubin-induced modulation of cerebral protein phosphorylation in neonate rabbits in vivo. Morphis, L., Constantopoulos, A., Matsaniotis, N., Papaphilis, A. Science (1982) [Pubmed]
  21. Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report. Sinclair, S.B., Greig, P.D., Blendis, L.M., Abecassis, M., Roberts, E.A., Phillips, M.J., Cameron, R., Levy, G.A. J. Clin. Invest. (1989) [Pubmed]
  22. Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro. Erps, L.T., Ritter, J.K., Hersh, J.H., Blossom, D., Martin, N.C., Owens, I.S. J. Clin. Invest. (1994) [Pubmed]
  23. Influence of glutathione S-transferase B (ligandin) on the intermembrane transfer of bilirubin. Implications for the intracellular transport of nonsubstrate ligands in hepatocytes. Zucker, S.D., Goessling, W., Ransil, B.J., Gollan, J.L. J. Clin. Invest. (1995) [Pubmed]
  24. Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding. Stollman, Y.R., Gärtner, U., Theilmann, L., Ohmi, N., Wolkoff, A.W. J. Clin. Invest. (1983) [Pubmed]
  25. Studies on the mechanism of Sn-protoporphyrin suppression of hyperbilirubinemia. Inhibition of heme oxidation and bilirubin production. Simionatto, C.S., Anderson, K.E., Drummond, G.S., Kappas, A. J. Clin. Invest. (1985) [Pubmed]
  26. Origin of mammalian biliprotein and rearrangement of bilirubin glucuronides in vivo in the rat. McDonagh, A.F., Palma, L.A., Lauff, J.J., Wu, T.W. J. Clin. Invest. (1984) [Pubmed]
  27. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. Belcher, J.D., Mahaseth, H., Welch, T.E., Otterbein, L.E., Hebbel, R.P., Vercellotti, G.M. J. Clin. Invest. (2006) [Pubmed]
  28. Physicochemical and immunohistological studies of a sulfobromophthalein- and bilirubin-binding protein from rat liver plasma membranes. Stremmel, W., Gerber, M.A., Glezerov, V., Thung, S.N., Kochwa, S., Berk, P.D. J. Clin. Invest. (1983) [Pubmed]
  29. Deleterious effect of prednisolone in HBsAg-positive chronic active hepatitis. Lam, K.C., Lai, C.L., Trepo, C., Wu, P.C. N. Engl. J. Med. (1981) [Pubmed]
  30. Heme oxygenase: a novel target for the modulation of the inflammatory response. Willis, D., Moore, A.R., Frederick, R., Willoughby, D.A. Nat. Med. (1996) [Pubmed]
  31. Uridine diphosphate-glucuronic acid-independent conversion of bilirubin monoglucuronides to diglucuronide in presence of plasma membranes from rat liver is nonenzymic. Sieg, A., van Hees, G.P., Heirwegh, K.P. J. Clin. Invest. (1982) [Pubmed]
  32. A family of drug transporters: the multidrug resistance-associated proteins. Borst, P., Evers, R., Kool, M., Wijnholds, J. J. Natl. Cancer Inst. (2000) [Pubmed]
  33. Dual hereditary jaundice: simultaneous occurrence of mutations causing Gilbert's and Dubin-Johnson syndrome. Cebecauerova, D., Jirasek, T., Budisova, L., Mandys, V., Volf, V., Novotna, Z., Subhanova, I., Hrebicek, M., Elleder, M., Jirsa, M. Gastroenterology (2005) [Pubmed]
  34. Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia. Huang, C.S., Chang, P.F., Huang, M.J., Chen, E.S., Chen, W.C. Gastroenterology (2002) [Pubmed]
  35. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Marschall, H.U., Wagner, M., Zollner, G., Fickert, P., Diczfalusy, U., Gumhold, J., Silbert, D., Fuchsbichler, A., Benthin, L., Grundström, R., Gustafsson, U., Sahlin, S., Einarsson, C., Trauner, M. Gastroenterology (2005) [Pubmed]
  36. Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Doré, S., Takahashi, M., Ferris, C.D., Zakhary, R., Hester, L.D., Guastella, D., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  37. The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites. Ochs, A., Rössle, M., Haag, K., Hauenstein, K.H., Deibert, P., Siegerstetter, V., Huonker, M., Langer, M., Blum, H.E. N. Engl. J. Med. (1995) [Pubmed]
  38. Jaundice phototherapy: micro flow-cell photometry reveals rapid biliary response of Gunn rats to light. McDonagh, A.F., Ramonas, L.M. Science (1978) [Pubmed]
  39. Irreversible binding of conjugated bilirubin to albumin in cholestatic rats. Gautam, A., Seligson, H., Gordon, E.R., Seligson, D., Boyer, J.L. J. Clin. Invest. (1984) [Pubmed]
  40. Identification of gallbladder mucin-bilirubin complex in human cholesterol gallstone matrix. Effects of reducing agents on in vitro dissolution of matrix and intact gallstones. Smith, B.F., LaMont, J.T. J. Clin. Invest. (1985) [Pubmed]
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