The presence of a microsomal UDP-glucuronyl transferase for bilirubin in homozygous jaundiced Gunn rats and in the Crigler-Najjar syndrome.

Abstract

The infusion of a closely related derivative of bilirubin, its dimethyl diester (DME), into jaundiced (jj) Gunn rats were associated with biliary excretion of mono- and diglucuronides of bilirubin. In vitro incubation of DME with liver microsomes from jj rats demonstrated sequential demethylation and glucuronidation of DME. Liver microsomes from a patient with the Crigler-Najjar syndrome were unable to form glucuronides of bilirubin in vitro unless DME was used as substrate. The results suggest that the deficiency in Gunn rats and in the Crigler-Najjar syndrome may be due to a structural defect in the microsomal matrix which contains glucuronyl transferase. This interpretation envisions a microenvironment of the transferase enzyme which is either impermeable to bilirubin or induces conformational changes which interfere with glucuronidation.

• Authors: G B Odell, J O Cukier, G R Gourley
• Journal: Hepatology (Baltimore, Md.) (Hepatology) 1981 Jul-Aug Vol. 1 Issue 4 Pg. 307-15 ISSN: 0270-9139 [Print] United States
• PMID: 6793495 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• bilirubin dimethyl ester
• Glucuronosyltransferase
• Bilirubin

Topics

• Adolescent
• Animals
• Bilirubin (analogs & derivatives, metabolism)
• Crigler-Najjar Syndrome (enzymology)
• Female
• Glucuronosyltransferase (metabolism)
• Humans
• Hyperbilirubinemia, Hereditary (enzymology)
• Microsomes, Liver (enzymology)
• Rats
• Rats, Gunn
• Rats, Inbred Strains