Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency.
Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency.
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DOI：
10.1182/blood.v81.12.3404.3404
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发表时间：
1993
期刊：
影响因子：
20.3
通讯作者：
S. Stabler;J. Lindenbaum;D. Savage;R. Allen
中科院分区：
文献类型：
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作者：
S. Stabler;J. Lindenbaum;D. Savage;R. Allen
同型半胱氨酸可以通过钴胺素（Cbl）和叶酸依赖酶蛋氨酸合成酶甲基化形成蛋氨酸；血清总同型半胱氨酸水平在95%以上的Cbl或叶酸缺乏症患者中升高。同型半胱氨酸也可以与丝氨酸在吡哆醛磷酸依赖反应中缩合形成胱氨酸，该反应由胱氨酸-合成酶催化。半胱硫氨酸随后被吡哆醛磷酸依赖酶γ -半胱硫氨酸酶裂解成半胱氨酸和α -酮丁酸盐。为了评估Cbl和叶酸缺乏症患者的胱胱甘氨酸水平，我们开发了一种新的毛细管气相色谱-质谱分析方法，并测量了正常受试者和临床证实这些维生素缺乏症患者血清中的胱胱甘氨酸。50名正常献血者血清胱硫氨酸正常范围为65 ~ 301 nmol/L（中位数为126 nmol/L）。在30例临床证实Cbl缺乏的患者中，胱硫氨酸的值在208 - 2920 nmol/L之间（中位数为816 nmol/L）， 26例（87%）高于正常范围。在20例临床证实叶酸缺乏的患者中，胱硫氨酸浓度在138 nmol/L至4150 nmol/L之间（中位数为1560 nmol/L）， 19例（95%）高于正常范围。5例半胱甘氨酸-合成酶缺乏症患者血清总同型半胱氨酸值高，血清半胱甘氨酸值低或低正常值，范围从30 nmol/L到114 nmol/L，即使他们接受吡哆醇治疗并有部分反应。1例5- ch3 -四氢叶酸合成缺陷患者和5例CH3-Cbl合成缺陷患者的血清总同型半胱氨酸和半胱硫氨酸的高值在311 nmol/L至1500 nmol/L之间，尽管他们分别接受叶酸和Cbl治疗，并有部分反应。我们的结论是，在大多数Cbl和叶酸缺乏症患者的血清中评估胱硫氨酸水平，并且它们在血清总同型半胱氨酸水平升高的鉴别诊断中是有用的。
Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3-tetrahydrofolate and five patients with defects in the synthesis of CH3-Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.