Document Detail


Is the increase in serum cystathionine levels in patients with liver cirrhosis a consequence of impaired homocysteine transsulfuration at the level of gamma-cystathionase?
MedLine Citation:
PMID:  10994627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: It has been suggested that the major metabolic block in the methionine catabolic pathway in cirrhotics exists at the level of the enzyme S-adenosylmethionine synthetase because in previous studies using conventional amino-acid analyzers, no intermediates of transmethylation/transsulfuration were found to accumulate in plasma downstream of S-adenosylmethionine synthesis. We therefore measured serum concentration intermediates of methionine transmethylation/transsulfuration using an improved gas chromatography/mass spectrometry technique. METHODS: Serum concentrations of methionine, homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, 2-methylcitric acid and alpha-aminobutyric acid were determined by gas chromatography/mass spectrometry in 108 consecutive patients with liver cirrhosis at Child stages A (mild cirrhosis, n = 27) and B/C (severe cirrhosis, n = 81), 18 outpatients with non-cirrhotic liver disease, and 55 healthy individuals. RESULTS: Serum levels of methionine, N,N-dimethylglycine, N-methylglycine, cystathionine, and homocysteine were significantly higher in patients at Child stages B/C compared with those of healthy controls (P < 0.01), and they were also significantly higher than in patients with non-cirrhotic liver disease (P < 0.01 and P < 0.05 for homocysteine, respectively). They also correlated with the Child-Pugh score (P < 0.01). Homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, and 2-methylcitric acid correlated with serum creatinine. The mean cystathionine concentration was significantly higher in patients with creatinine > or = 1.4 mg/dl than in patients with normal creatinine values (P < 0.01). However, the differences between cirrhotics and healthy controls were still significant after correcting for creatinine. CONCLUSIONS: Our data provides indirect evidence for two hitherto unrecognized alterations of methionine metabolism in cirrhotics, i.e. impairment of the transsulfuration of homocysteine at the level of cystathionine degradation and a shift in remethylation of homocysteine towards the betaine-homocysteine-methyltransferase reaction.
Authors:
M P Look; R Riezler; C Reichel; K A Brensing; J K Rockstroh; S P Stabler; U Spengler; H K Berthold; T Sauerbruch
Related Documents :
9737577 - Bile acids influence hepatic chemiluminescence in normal and oxidative-stressed rats.
19103957 - Lithocholic acid as a biomarker of intrahepatic cholestasis of pregnancy during ursodeo...
6839487 - 125i radioimmunoassay of serum ursodeoxycholyl conjugates.
10446117 - Bile acid patterns in meconium are influenced by cholestasis of pregnancy and not alter...
16339957 - Medium- to large-sized xylo-oligosaccharides are responsible for xylanase induction in ...
15853397 - Isolation, characterization, and antioxidant activity of e- and z-p-coumaryl fatty acid...
Publication Detail:
Type:  Clinical Trial; Comparative Study; Controlled Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Scandinavian journal of gastroenterology     Volume:  35     ISSN:  0036-5521     ISO Abbreviation:  Scand. J. Gastroenterol.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2001-01-11     Completed Date:  2001-01-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0060105     Medline TA:  Scand J Gastroenterol     Country:  NORWAY    
Other Details:
Languages:  eng     Pagination:  866-72     Citation Subset:  IM    
Affiliation:
Dept. of Internal Medicine I, University of Bonn, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Analysis of Variance
Biological Markers / blood
Chromatography, Gas
Cystathionine / analysis,  blood*
Cystathionine gamma-Lyase / metabolism*
Female
Gas Chromatography-Mass Spectrometry
Homocysteine / metabolism*
Humans
Liver Cirrhosis / diagnosis*,  enzymology*
Male
Middle Aged
Probability
Reference Values
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
AG-09834/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 454-28-4/Homocysteine; 56-88-2/Cystathionine; EC 4.4.1.1/Cystathionine gamma-Lyase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Prevalence and clinical spectrum of chronic viral hepatitis in a middle-aged Swedish general urban p...
Next Document:  Intravenous bilirubin, dibromosulfophthalein, and bromosulfophthalein infusions uncouple biliary pho...