J Clin Invest. 1990 Apr;85(4):1199-205.

Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I.

van Es HH, Goldhoorn BG, Paul-Abrahamse M, Elferink RP, Jansen PL.

Source

Division of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.

Abstract

The functional heterogeneity of uridine diphosphate-glucuronosyltransferase (UDPGT) and its deficiency in human liver were investigated. The monoclonal antibody (MAb) WP1, which inhibits bilirubin and phenol-glucuronidating activity, was used to immunopurify UDPGTs from human liver. Purified UDPGTs were injected into mice to obtain new MAbs. Immunoblotting of microsomes with MAb HEB7 revealed at least three polypeptides in liver (56, 54, and 53 kD) and one in kidney (54 kD). In liver microsomes from four patients (A, B, C, and D) with Crigler-Najjar syndrome type I (CN type I), UDPGT activity towards bilirubin was undetectable (A, B, C, and D) and activity towards phenolic compounds and 5-hydroxytryptamine either reduced (A and B) or normal (C and D). UDPGT activity toward steroids was normal. Immunoblot studies revealed that the monoclonal antibody WP1 recognized two polypeptides (56 and 54 kD) in liver microsomes from patient A and none in patient B. With HEB7 no immunoreactive polypeptides were seen in these two patients. Patient C showed a normal banding pattern and in patient D only the 53-kD band showed decreased intensity. These findings suggest considerable heterogeneity with regard to the expression of UDPGT isoenzymes among CN type I patients.

PMID:: 2108190; [PubMed - indexed for MEDLINE]
PMCID:: PMC296552

Free PMC Article

MeSH Terms, Substances

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Crigler-Najjar syndrome - Genetics Home Reference

Supplemental Content

Icon for Journal of Clinical Investigation

Save items

Related citations in PubMed

Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. [J Clin Invest. 1994]
Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.
Seppen J, Bosma PJ, Goldhoorn BG, Bakker CT, Chowdhury JR, Chowdhury NR, Jansen PL, Oude Elferink RP. J Clin Invest. 1994 Dec; 94(6):2385-91.
Review Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyltransferase in Crigler-Najjar syndrome. [J Inherit Metab Dis. 1991]
Review Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyltransferase in Crigler-Najjar syndrome.
Robertson KJ, Clarke D, Sutherland L, Wooster R, Coughtrie MW, Burchell B. J Inherit Metab Dis. 1991; 14(4):563-79.
The presence of a microsomal UDP-glucuronyl transferase for bilirubin in homozygous jaundiced Gunn rats and in the Crigler-Najjar syndrome. [Hepatology. 1981]
The presence of a microsomal UDP-glucuronyl transferase for bilirubin in homozygous jaundiced Gunn rats and in the Crigler-Najjar syndrome.
Odell GB, Cukier JO, Gourley GR. Hepatology. 1981 Jul-Aug; 1(4):307-15.
A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II. [Gastroenterology. 1993]
A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II.
Bosma PJ, Goldhoorn B, Oude Elferink RP, Sinaasappel M, Oostra BA, Jansen PL. Gastroenterology. 1993 Jul; 105(1):216-20.
Review Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. [Hum Mutat. 2000]
Review Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.
Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR. Hum Mutat. 2000 Oct; 16(4):297-306.

See reviews... See all...

Cited by 6 PubMed Central articles

Role of cysteine residues in the function of human UDP glucuronosyltransferase isoform 1A1 (UGT1A1). [Biochem J. 2005]
Role of cysteine residues in the function of human UDP glucuronosyltransferase isoform 1A1 (UGT1A1).
Ghosh SS, Lu Y, Lee SW, Wang X, Guha C, Roy-Chowdhury J, Roy-Chowdhury N. Biochem J. 2005 Dec 15; 392(Pt 3):685-92.
Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen. [Gut. 2004]
Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen.
Dietrich CG, Geier A, Wasmuth HE, Matern S, Gartung C, de Waart DR, Elferink RP. Gut. 2004 Dec; 53(12):1850-5.
Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syndrome type I: implication in carrier detection and prenatal diagnosis. [Am J Hum Genet. 1993]
Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syndrome type I: implication in carrier detection and prenatal diagnosis.
Moghrabi N, Clarke DJ, Burchell B, Boxer M. Am J Hum Genet. 1993 Sep; 53(3):722-9.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Gene (OMIM)
Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
OMIM (cited)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
References for this PMC Article
Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
Free in PMC
Free full text articles in PMC
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four p...
Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I.
J Clin Invest. 1990 Apr ;85(4):1199-205.

PubMed
Downregulation of microRNA-29c is associated with hypermethylation of tumor-rela...
Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma.
Epigenetics. 2011 Mar ;6(3):388-94. Epub 2011 Mar 1 .

PubMed
Preoperative endoscopic airway examination (PEAE) provides superior airway infor...
Preoperative endoscopic airway examination (PEAE) provides superior airway information and may reduce the use of unnecessary awake intubation.
Anesth Analg. 2011 Mar ;112(3):602-7. Epub 2010 Nov 16 .

PubMed
ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capa...
ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capacity.
Mol Cell Endocrinol. 2010 Oct 26 ;328(1-2):104-8. Epub 2010 Jul 23 .

PubMed
Cysteine-to-serine mutants dramatically reorder the active site of human ABO(H) ...
Cysteine-to-serine mutants dramatically reorder the active site of human ABO(H) blood group B glycosyltransferase without affecting activity: structural insights into cooperative substrate binding.
J Mol Biol. 2010 Sep 17 ;402(2):399-411. Epub 2010 Jul 23 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: