Bilirubin glucuronidation

MRP2 (ABCC2) LTC4, bilirubin-glucuronide, estradiol 17 3-glucuronide, dianionic bile salts, anionic conjugates, glutathione disulfide, and others... 

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

SN-38 glucuronidation is catalyzed by the polymorphic UDP-glucuronosyltransfer-ase 1A1 (UGT1A1) enzyme, which is responsible for bilirubin glucuronidation... 

Iyer, L., HaU, D., Das, S., et al. (1999) Phenotype-genotype correlation of in vitro SN-38 (active metabohte of iiinotecan) and bilirubin glucuronidation in human liver tissue with UGTIAI promoter polymorphism. Clin. Pharmacol. Ther. 65, 576-582. 

A8. Arias, I. M., and London, I. M., Bilirubin glucuronide formation in vitro demonstration of a defect in Gilbert s disease. Science 126, 563-564 (1957). 

Fll. Flodgaard, H. J., and Brodersen, R., Bilirubin glucuronide formation in developing guinea pig liver. Scand. J. Clin. Lab. Invest. 19, 149-155 (1967). 

Jl. Jacobsen, J., A chromatographic separation of bilirubin glucuronides from human bile. Acta Chim. Scand. 23, 3023-3026 (1969). 

P4. Potrepka, R. F., and Spratt, J. L., Bilirubin glucuronidation by hepatic microsomal subfractions and the effect of 3-methylcholanthrene. Biochem. Pharmacol. 20, 2247-2252 (1971). 

Schmid, R., The identification of direct-reacting bilirubin as bilirubin glucuronide. J. Biol. Chem. 229, 881-888 (1957). 

Schmid, R., Hammaker, L., and Axelrod, J., The enzymatic formation of bilirubin glucuronide. Arch. Biochem. Biophys. 70, 285-288 (1957). 

Alterations in the metabolism of heme. A. Hemolytic jaundice. B. Neonatal jaundice. [Note The enterohepatic circulation of urobilinogen is omitted for simplicity.] BG = bilirubin glucuronide B = bilirubin U = urobilinogen S = stercobilin. 

Bilirubin glucuronide 1 i Bilirubin t Urobilinogen 1 j Stercobilin Urobilin Bilirubin glucuronide Bilrubin INTESTINE 1 Urobilinogen Stercobilin Urobilin... 

It has now been established that in common with many other glu-curonides, bilirubin glucuronide can be synthesized in the adult rat, rabbit, mouse, and guinea pig liver by the enzymatic transfer of glucuronic acid from uridine diphosphate glucuronic acid to an acceptor substance, namely, bilirubin (Fig. 3) (B17, G5, L3, L5, S8). The transferring enzyme (glucuronyl transferase) has been shown by Schmid et al. 

Fig. 6. Direct-reacting bilirubin glucuronide production by liver preparations from normal rats and human beings and from patients with constitutional hepatic dysfunction (Gilbert s disease) (A4).

Fig. 7. Bilirubin excretion in the bile of a jaundiced rat after intravenous injections of bilirubin and bilirubin glucuronide (S10).

Schmid, R., Direct-reacting bilirubin, bilirubin glucuronide in serum, bile, and urine. Science 124, 76-77 (1956). 

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