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    
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.
M P Look; R Riezler; C Reichel; K A Brensing; J K Rockstroh; S P Stabler; U Spengler; H K Berthold; T Sauerbruch
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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    
Dept. of Internal Medicine I, University of Bonn, Germany.
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MeSH Terms
Analysis of Variance
Biological Markers / blood
Chromatography, Gas
Cystathionine / analysis,  blood*
Cystathionine gamma-Lyase / metabolism*
Gas Chromatography-Mass Spectrometry
Homocysteine / metabolism*
Liver Cirrhosis / diagnosis*,  enzymology*
Middle Aged
Reference Values
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
Grant Support
Reg. No./Substance:
0/Biological Markers; 454-28-4/Homocysteine; 56-88-2/Cystathionine; EC gamma-Lyase

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

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