Tchantchou Flaubert, Shea Thomas B
University of Maryland, Baltimore, Maryland, USA.
Vitam Horm. 2008;79:83-97. doi: 10.1016/S0083-6729(08)00403-2.
Folate deficiency is associated with increase in homocysteine levels. Abnormal plasma levels of that neurotoxic nonproteinogenic amino acid is implicated in many pathological conditions including cardiovascular diseases, neural tube defects, and is now recognized as a risk factor in Alzheimer's disease (AD) dementia. Homocysteine elimination is regulated by two metabolic pathways, namely, the transmethylation and the transsulfuration pathways. Its elimination via these two metabolic pathways is modulated by folate, a member of the B-vitamin family. Folate provides, via its metabolic end product 5-methyltetrahydrofolate, a methyl group that is used to reconvert homocysteine back to methionine through the transmethylation pathway. The efficiency of folate metabolism has an impact on the availability of S-adenosylmethionine, a compound that is known to activate homocysteine flux through the transsulfuration pathway and is necessary for utilization of a downstream antioxidant called glutathione under the catalysis of glutathione S-transferase enzyme. In this review, we will explore the impact of folate deprivation on the regulation of the methionine cycle and exhaustively describe different biochemical reactions that are implicated in the regulation of homocysteine elimination and that folate deficiency influences in AD neuropathology.
叶酸缺乏与同型半胱氨酸水平升高有关。这种具有神经毒性的非蛋白质氨基酸的血浆水平异常与许多病理状况相关，包括心血管疾病、神经管缺陷，并且现在被认为是阿尔茨海默病（AD）痴呆的一个风险因素。同型半胱氨酸的清除由两条代谢途径调节，即转甲基化途径和转硫化途径。通过这两条代谢途径对其清除的调节受B族维生素家族成员叶酸的影响。叶酸通过其代谢终产物5-甲基四氢叶酸提供一个甲基，该甲基用于通过转甲基化途径将同型半胱氨酸重新转化为甲硫氨酸。叶酸代谢的效率会影响S-腺苷甲硫氨酸的可用性，S-腺苷甲硫氨酸是一种已知可通过转硫化途径激活同型半胱氨酸通量的化合物，并且在谷胱甘肽S-转移酶的催化下是利用下游抗氧化剂谷胱甘肽所必需的。在本综述中，我们将探讨叶酸缺乏对甲硫氨酸循环调节的影响，并详尽描述与同型半胱氨酸清除调节相关且叶酸缺乏在AD神经病理学中产生影响的不同生化反应。
