Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1978 Jul;62(1):191–196. doi: 10.1172/JCI109105

Hepatic Conversion of Bilirubin Monoglucuronide to Diglucuronide in Uridine Diphosphate-Glucuronyl Transferase-Deficient Man and Rat by Bilirubin Glucuronoside Glucuronosyltransferase

J Roy Chowdhury 1, P L M Jansen 1, E B Fischberg 1, A Daniller 1, I M Arias 1
PMCID: PMC371753  PMID: 96142

Abstract

The microsomal enzyme uridine diphosphate (UDP) glucuronate glucuronyltransferase (E.C. 2.4.1.17) catalyzes formation of bilirubin mono-glucuronide from bilirubin and UDPglucuronic acid. Bilirubin glucuronoside glucuronosyltransferase (E.C. 2.4.1.95), an enzyme concentrated in plasma membrane-enriched fractions of rat liver, converts bilirubin monoglucuronide to bilirubin diglucuronide. Bilirubin glucuronoside glucuronosyltransferase activity was studied in homogenates of liver biopsy specimens obtained from patients with the Crigler-Najjar syndrome (Type I) and in subcellular liver fractions of rats homozygous for UDP glucuronate glucuronyltransferase deficiency (Gunn strain). In patients with the Crigler-Najjar syndrome (Type I) and in Gunn rats, hepatic UDPglucuronate glucuronyltransferase activity was not measurable; however, bilirubin glucuronoside glucuronosyltransferase activity was similar to that in normal controls. The subcellular distribution of bilirubin glucuronoside glucuronosyltransferase activity in Gunn rat liver was similar to the distribution observed in normal Wistar rat liver.

When bilirubin monoglucuronide was infused intravenously into Gunn rats, 29±5% of the conjugated bilirubin excreted in bile was bilirubin diglucuronide. After transplantation of normal Wistar rat kidney, which contained UDPglucuronate glucuronyltransferase activity, in Gunn rats, the serum bilirubin concentration decreased by 80% in 4 days. The major route of bilirubin removal was biliary excretion of conjugated bilirubin, approximately 70% of which was bilirubin diglucuronide. Although patients with the Crigler-Najjar syndrome (Type I) and Gunn rats lack UDP glucuronate glucuronyltransferase, their livers enzymatically convert bilirubin monoglucuronide to diglucuronide in vitro. Conversion in bilirubin monoglucuronide to diglucuronide was demonstrated in Gunn rats in vivo.

Full text

PDF
192

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARIAS I. M., JOHNSON L., WOLFSON S. Biliary excretion of injected conjugated and unconjugated bilirubin by normal and Gunn rats. Am J Physiol. 1961 May;200:1091–1094. doi: 10.1152/ajplegacy.1961.200.5.1091. [DOI] [PubMed] [Google Scholar]
  2. AXELROD J., SCHMID R., HAMMAKER L. A biochemical lesion in congenital, nonobstructive, non-haemolytic jaundice. Nature. 1957 Dec 21;180(4599):1426–1427. doi: 10.1038/1801426a0. [DOI] [PubMed] [Google Scholar]
  3. Arias I. M., Gartner L. M., Cohen M., Ezzer J. B., Levi A. J. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med. 1969 Sep;47(3):395–409. doi: 10.1016/0002-9343(69)90224-1. [DOI] [PubMed] [Google Scholar]
  4. BILLING B. H., COLE P. G., LATHE G. H. The excretion of bilirubin as a diglucuronide giving the direct van den Bergh reaction. Biochem J. 1957 Apr;65(4):774–784. doi: 10.1042/bj0650774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black M., Billing B. H., Heirwegh K. P. Determination of bilirubin UDP-glucuronyl transferase activity in needle-biopsy specimens of human liver. Clin Chim Acta. 1970 Jul;29(1):27–35. doi: 10.1016/0009-8981(70)90216-0. [DOI] [PubMed] [Google Scholar]
  6. Foliot A., Christoforov B., Petite J. P., Etienne J. P., Housset E., Dubois M. Bilirubin UDP-glucuronyltransferase activity of wistar rat kidney. Am J Physiol. 1975 Aug;229(2):340–343. doi: 10.1152/ajplegacy.1975.229.2.340. [DOI] [PubMed] [Google Scholar]
  7. HARTIALA K. J., PULKKINEN M. O., SAVOLA P. BETA-D-GLUCOSIDURONIC ACID CONJUGATION BY THE MUCOSA OF VARIOUS ORGANS. Nature. 1964 Mar 7;201:1036–1036. doi: 10.1038/2011036a0. [DOI] [PubMed] [Google Scholar]
  8. Heirwegh K. P., Van Hees G. P., Leroy P., Van Roy F. P., Jansen F. H. Heterogeneity of bile pigment conjugates as revealed by chromatography of their ethyl anthranilate azopigments. Biochem J. 1970 Dec;120(4):877–890. doi: 10.1042/bj1200877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jansen P. L., Chowdhury J. R., Fischberg E. B., Arias I. M. Enzymatic conversion of bilirubin monoglucuronide to diglucuronide by rat liver plasma membranes. J Biol Chem. 1977 Apr 25;252(8):2710–2716. [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. OWEN J. A., IGGO B., SCANDRETT F. J., STEWART C. P. The determination of creatinine in plasma or serum, and in urine; a critical examination. Biochem J. 1954 Nov;58(3):426–437. doi: 10.1042/bj0580426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ostrow J. D. Photocatabolism of labeled bilirubin in the congenitally jaundiced (Gunn) rat. J Clin Invest. 1971 Mar;50(3):707–718. doi: 10.1172/JCI106541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. STEVENSON I. H., DUTTON G. J. Glucuronide synthesis in kidney and gastrointestinal tract. Biochem J. 1962 Feb;82:330–340. doi: 10.1042/bj0820330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. SWANSON M. A. Phosphatases of liver. I. Glucose-6-phosphatase. J Biol Chem. 1950 Jun;184(2):647–659. [PubMed] [Google Scholar]
  15. Touster O., Aronson N. N., Jr, Dulaney J. T., Hendrickson H. Isolation of rat liver plasma membranes. Use of nucleotide pyrophosphatase and phosphodiesterase I as marker enzymes. J Cell Biol. 1970 Dec;47(3):604–618. doi: 10.1083/jcb.47.3.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Van Roy F. P., Heirwegh K. P. Determination of bilirubin glucuronide and assay of glucuronyltransferase with bilirubin as acceptor. Biochem J. 1968 Apr;107(4):507–518. doi: 10.1042/bj1070507. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES