Biochemical and molecular aspects of genetic disorders of bilirubin metabolism.

Abstract

Bilirubin, the oxidative product of heme in mammals, is excreted into the bile after its esterification with glucuronic acid to polar mono- and diconjugated derivatives. The accumulation of unconjugated and conjugated bilirubin in the serum is caused by several types of hereditary disorder. The Crigler-Najjar syndrome is caused by a defect in the gene which encodes bilirubin UDP-glucuronosyltransferase (UGT), whereas the Dubin-Johnson syndrome is characterized by a defect in the gene which encodes the canalicular bilirubin conjugate export pump of hepatocytes. Animal models such as the unconjugated hyperbilirubinemic Gunn rat, the conjugated hyperbilirubinemic GY/TR-, and the Eisai hyperbilirubinemic rat, have contributed to the understanding of the molecular basis of hyperbilirubinemia in humans. Elucidation of both the structure of the UGT1 gene complex, and the Mrp2 (cMoat) gene which encodes the canalicular conjugate export pump, has led to a greater understanding of the genetic basis of hyperbilirubinemia.

• Authors: T Iyanagi, Y Emi, S Ikushiro
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1407 Issue 3 Pg. 173-84 (Sep 30 1998) ISSN: 0006-3002 [Print] Netherlands
• PMID: 9748558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anion Transport Proteins
• Carrier Proteins
• bilirubin glucuronate
• Heme
• Glucuronosyltransferase
• Bilirubin

Topics

• Animals
• Anion Transport Proteins
• Bile (metabolism)
• Bilirubin (analogs & derivatives, genetics, metabolism)
• Carrier Proteins (metabolism)
• Disease Models, Animal
• Glucuronosyltransferase (metabolism)
• Heme (metabolism)
• Humans
• Hyperbilirubinemia, Hereditary (genetics, metabolism)
• Rats
• Rats, Gunn