Metabolic consequences of folate-induced reduction of hyperhomocysteinemia in uremia.
Metabolic consequences of folate-induced reduction of hyperhomocysteinemia in uremia.
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叶酸诱导尿毒症高同型半胱氨酸血症减少的代谢后果。
DOI：
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发表时间：
1997
影响因子：
13.6
通讯作者：
V. Zappia
中科院分区：
文献类型：
--
作者：
A. Perna;D. Ingrosso;N. Santo;P. Galletti;M. Brunone;V. Zappia
血浆同型半胱氨酸是公认的心血管疾病危险因素，在接受血液透析的尿毒症患者中血浆同型半胱氨酸升高。作者最近证明，一个后果是红细胞膜蛋白甲基化水平降低，这是由细胞内腺苷同型半胱氨酸（一种有效的甲基转移酶抑制剂）的增加引起的。蛋白质甲基化参与受损膜蛋白的修复机制，甲基化受损会导致改变的蛋白质的积累。叶酸是同型半胱氨酸转化为蛋氨酸的辅助因子，叶酸治疗可有效降低血浆同型半胱氨酸。本文详细介绍了口服甲基四氢叶酸（叶酸的活性形式）对 14 名尿毒症血液透析患者的代谢影响的研究。两个月的治疗导致血浆同型半胱氨酸水平显着降低，与叶酸前水平成比例反应。在 13 名同型半胱氨酸水平高于 20 µM 的患者中，有 5 名患者的血浆同型半胱氨酸水平降至低于 15 µM。治疗后，腺苷甲硫氨酸（甲基转移中的甲基供体）的水平显着增加；腺苷同型半胱氨酸水平增加幅度较小。因此，两种化合物之间的比率（甲基化抑制的存在和程度的极好指标）显着改善。所有患者治疗后血浆蛋氨酸水平均升高，且与治疗后腺苷蛋氨酸水平相关。结论是，用甲基四氢叶酸治疗使血浆同型半胱氨酸浓度回到“可接受的”水平，并且代谢结果朝着正常转甲基流增加的方向，如通过[腺苷甲硫氨酸]/[腺苷同型半胱氨酸]比率的增加来监测。
Plasma homocysteine, a well-recognized risk factor for cardiovascular disease, is elevated in uremic patients on hemodialysis. The authors have recently demonstrated that one consequence is the reduction in red cell membrane protein methylation levels, caused by a rise of intracellular adenosylhomocysteine, a potent inhibitor of methyltransferases. Protein methylation is involved in a repair mechanism of damaged membrane proteins, and an impairment in methylation leads to the accumulation of altered proteins. Therapy with folates, cofactors in the transformation of homocysteine to methionine, is effective in lowering plasma homocysteine. This article details a study on the metabolic effects of oral methyltetrahydrofolate, the active form of folic acid, on 14 uremic hemodialysis patients. Two months of therapy led to a significant reduction of plasma homocysteine levels, with a proportional response to pre-folate levels. In five of 13 patients with homocysteine levels above 20 microM, plasma homocysteine level was reduced to less than 15 microM. After treatment, levels of adenosylmethionine, the methyl donor in transmethylations, had significantly increased; levels of adenosylhomocysteine had increased to a smaller extent. Therefore, the ratio between the two compounds, an excellent indicator of the presence and the degree of methylation inhibition, was significantly ameliorated. Methionine plasma levels increased after treatment in all patients and were correlated with posttreatment adenosylmethionine levels. It was concluded that treatment with methyltetrahydrofolate brings the plasma homocysteine concentration back to an "acceptable" level, and the metabolic consequences are in the direction of an increase in the normal flow of transmethylations, as monitored by an increase in the [adenosylmethionine]/[adenosylhomocysteine] ratio.
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S-腺苷-L-同型半胱氨酸在完整红细胞中抑制蛋白质羧基甲基化。
DOI：
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发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Barber,JR;Clarke,S
通讯作者：
Clarke,S
DOI：
10.1001/jama.1992.03490070059042
发表时间：
1992-08
期刊：
JAMA
影响因子：
--
作者：
M. Stampfer;M. Malinow;W. Willett;L. Newcomer;B. Upson;D. Ullmann;P. Tishler;C. Hennekens
通讯作者：
M. Stampfer;M. Malinow;W. Willett;L. Newcomer;B. Upson;D. Ullmann;P. Tishler;C. Hennekens
影响因子：
37.8
作者：
ROBINSON, K;MAYER, EL;JACOBSEN, DW
通讯作者：
JACOBSEN, DW
影响因子：
37.8
作者：
MALINOW, MR;NIETO, FJ;BOND, G
通讯作者：
BOND, G
影响因子：
37.8
作者：
Robinson, K;Gupta, A;Jacobsen, DW
通讯作者：
Jacobsen, DW