Biochemical and molecular aspects of genetic disorders of bilirubin metabolism

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1407

Review

Iyanagi, T ; Emi, Y ; Ikushiro, S

关键词: bilirubin;    hyperbilirubinemia;    UDP-glucuronosyltransferase;    Gunn rat;    Crigler-Najjar syndrome;    gene therapy;    multidrug resistance protein 2;    GY/TR- rat;    Dubin-Johnson syndrome;   

DOI  :  10.1016/S0925-4439(98)00044-1

来源: Elsevier

【 摘 要 】

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-Naijar 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. (C) 1998 Elsevier Science B.V. All rights reserved.

【 授权许可】

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