Is the increase in serum cystathionine levels in patients with liver cirrhosis a consequence of impaired homocysteine transsulfuration at the level of gamma-cystathionase?
Is the increase in serum cystathionine levels in patients with liver cirrhosis a consequence of impaired homocysteine transsulfuration at the level of gamma-cystathionase?
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DOI：
10.1080/003655200750023255
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发表时间：
2000-08
影响因子：
1.9
通讯作者：
M. Look;R. Riezler;C. Reichel;K. Brensing;J. Rockstroh;S. Stabler;U. Spengler;H. Berthold;Tilman Sauerbruch
中科院分区：
文献类型：
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作者：
M. Look;R. Riezler;C. Reichel;K. Brensing;J. Rockstroh;S. Stabler;U. Spengler;H. Berthold;Tilman Sauerbruch
背景已经表明，在代谢障碍患者中甲硫氨酸分解代谢途径中的主要代谢阻断存在于酶S-腺苷甲硫氨酸合成酶的水平，因为在使用常规氨基酸分析仪的先前研究中，没有发现转甲基化/转硫作用的中间体在S-腺苷甲硫氨酸合成的血浆下游积累。因此，我们测量血清浓度中间体蛋氨酸转甲基/转硫使用改进的气相色谱/质谱技术。方法采用气相色谱/质谱联用法测定108例肝硬化ChildA期患者血清蛋氨酸、同型半胱氨酸、胱硫醚、N，N-二甲基甘氨酸、N-甲基甘氨酸、甲基丙二酸、2-甲基柠檬酸和α-氨基丁酸的浓度（轻度肝硬化，n = 27）和B/C（重度肝硬化，n = 81），18例门诊非硬化性肝病患者和55例健康个体。结果与正常对照组相比，Child分期B/C组患者血清蛋氨酸、N，N-二甲基甘氨酸、N-甲基甘氨酸、胱硫醚和同型半胱氨酸水平显著升高（P < 0.01），肌酐正常组患者血清蛋氨酸、N，N-二甲基甘氨酸、N-甲基甘氨酸、胱硫醚和同型半胱氨酸水平显著升高（P < 0.01）。然而，校正肌酐后，糖尿病患者和健康对照组之间的差异仍然显著。结论：我们的数据提供了间接证据，两个迄今未被认识到的改变蛋氨酸代谢的astritics，即损伤的transsulfurization同型半胱氨酸在胱硫醚降解的水平和转移同型半胱氨酸的再甲基化的甜菜碱同型半胱氨酸甲基转移酶反应。
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 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.