Methoxistasis: integrating the roles of homocysteine and folic acid in cardiovascular pathobiology.
Methoxistasis: integrating the roles of homocysteine and folic acid in cardiovascular pathobiology.
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DOI：
10.3390/nu5083235
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发表时间：
2013-08-15
期刊：
影响因子：
5.9
通讯作者：
Loscalzo J
中科院分区：
文献类型：
--
作者：
Joseph J;Loscalzo J
在过去的四十年中，蛋氨酸-同型半胱氨酸循环和相关叶酸代谢的异常引起了极大的兴趣，由于高同型半胱氨酸血症和人类病理学，特别是动脉粥样硬化血栓形成性心血管疾病之间的联系。然而，包括高剂量叶酸在内的B族维生素补充剂的临床试验尚未证明在预防或治疗心血管疾病方面有任何益处。除了这些临床试验的持续时间可能比调节慢性疾病状态的持续时间短之外，降低血液同型半胱氨酸水平可能是一种过于简化的复杂生物扰动方法。甲硫氨酸-高半胱氨酸循环和叶酸代谢调节氧化还原和甲基化反应，反过来又受氧化还原和甲基化状态调节。在正常情况下，存在正常的氧化还原-甲基化平衡或“甲氧稳态”，由甲硫氨酸-同型半胱氨酸循环协调。病理状态下的异常同型半胱氨酸水平可能反映了甲氧代谢紊乱。我们建议，未来的研究应针对估计从甲氧稳态的偏差，以及如何最好地恢复它。这种方法可能会导致预防和治疗心血管疾病，包括心力衰竭的重大进展。
Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.
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