The methionine-homocysteine cycle and its effects on cognitive diseases.
The methionine-homocysteine cycle and its effects on cognitive diseases.
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发表时间：
2003-02
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通讯作者：
Alan L. Miller
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作者：
Alan L. Miller
同型半胱氨酸是一种含硫氨基酸，是必需氨基酸蛋氨酸的代谢物，存在于蛋氨酸循环的关键生化交叉点- s -腺苷蛋氨酸，必不可少的无处不在的甲基供体，维生素B12和叶酸之间。血液中高水平的同型半胱氨酸预示着这一重要过程的崩溃，从而导致深远的生化和生命后果。同型半胱氨酸与心血管疾病之间的联系已得到充分证实，通过为其代谢提供营养辅助因子来降低血浆总同型半胱氨酸已被证明可降低心血管事件的风险。关于同型半胱氨酸代谢与认知功能之间联系的信息已经出现，从轻度认知能力下降（与年龄相关的记忆丧失）到血管性痴呆和阿尔茨海默病。同型半胱氨酸再甲基化辅助因子钴胺素（B12）和叶酸以及反式硫酸辅助因子维生素B6的显著缺乏在老年人中很常见，随着年龄的增长，同型半胱氨酸也随之增加。高同型半胱氨酸血症已被证明是认知功能障碍的独立危险因素。同型半胱氨酸可引起间接和直接的血管损伤，这与血管性痴呆有关，随着同型半胱氨酸水平的升高，多发脑梗死和痴呆的风险增加。人们发现，患阿尔茨海默病的风险与血浆中高水平的同型半胱氨酸、低水平的叶酸、维生素B6和B12之间存在显著的相关性。所有这些疾病关联被认为是通过增加同型半胱氨酸和s -腺苷型同型半胱氨酸以及随后的许多物质（包括DNA和蛋白质）的低甲基化而相互关联的，这些物质使血管结构和神经元更容易受到损伤和凋亡。为蛋氨酸循环的正常运作提供营养辅助因子可以改善甲基化并保护大脑免受损伤。需要进行进一步的研究来评估这是否也会降低认知疾病的风险和/或改善认知功能。
Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine, and exists at a critical biochemical intersection in the methionine cycle - between S-adenosylmethionine, the indispensable ubiquitous methyl donor, and vitamins B12 and folic acid. High blood levels of homocysteine signal a breakdown in this vital process, resulting in far-reaching biochemical and life consequences. The link between homocysteine and cardiovascular disease is well established, and decreasing plasma total homocysteine by providing nutritional cofactors for its metabolism has been shown to reduce the risk of cardiovascular events. Information has been emerging regarding a connection between homocysteine metabolism and cognitive function, from mild cognitive decline (age-related memory loss) to vascular dementia and Alzheimer's disease. Significant deficiencies in the homocysteine re-methylation cofactors cobalamin (B12) and folate, as well as the trans-sulfuration cofactor vitamin B6, are commonly seen in the elderly population, with a resultant increase in homocysteine with advancing age. Hyperhomocysteinemia has been shown to be an independent risk factor for cognitive dysfunction. Indirect and direct vascular damage can be caused by homocysteine, which has been implicated in vascular dementia, with an increased risk of multiple brain infarcts and dementia as homocysteine levels rise. A significant correlation has been found between risk of Alzheimer's disease and high plasma levels of homocysteine, as well as low levels of folic acid, and vitamins B6 and B12. All of these disease associations are thought to be interrelated via increased homocysteine and S-adenosylhomocysteine and subsequent hypomethylation of numerous substances, including DNA and proteins, that render vascular structures and neurons more susceptible to damage and apoptosis. Providing the nutritional cofactors for proper functioning of the methionine cycle may improve methylation and protect the brain from damage. Further studies need to be performed to assess whether this will also reduce the risk of cognitive diseases and/or improve cognitive functioning.