Tchantchou Flaubert
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
J Alzheimers Dis. 2006 Aug;9(4):421-7. doi: 10.3233/jad-2006-9408.
Homocysteine is a neurotoxic non-proteinogenic amino acid, an abnormal increase of which in plasma has been implicated in many pathological conditions including cardiovascular diseases, neural tube defects and is now recognized and Alzheimer's disease. Homocysteine elimination is regulated by the transmethylation and the transsulfuration pathways and is modulated by folate, a member of the B-vitamin family. A metabolic product of folate, 5 methyltetrahydrofolate, provides 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 (SAM), a compound that is known to activate homocysteine flux through the transsulfuration pathway. SAM is also necessary for utilization of the antioxidant glutathione via glutathione S-transferase. In this review, I will elaborate on different biochemical reactions that are implicated in the regulation of homocysteine elimination through the transmethylation and the transsulfuration pathways and on various consequences of folate deficiency on homocysteine metabolism.
同型半胱氨酸是一种具有神经毒性的非蛋白氨基酸，血浆中其水平异常升高与包括心血管疾病、神经管缺陷在内的多种病理状况有关，目前还被认为与阿尔茨海默病有关。同型半胱氨酸的清除受转甲基化和转硫途径调控，并受B族维生素家族成员叶酸的调节。叶酸的一种代谢产物5-甲基四氢叶酸提供一个甲基，该甲基通过转甲基化途径用于将同型半胱氨酸重新转化为甲硫氨酸。叶酸代谢效率会影响S-腺苷甲硫氨酸（SAM）的可用性，SAM是一种已知可通过转硫途径激活同型半胱氨酸通量的化合物。SAM对于通过谷胱甘肽S-转移酶利用抗氧化剂谷胱甘肽也是必需的。在本综述中，我将详细阐述通过转甲基化和转硫途径参与同型半胱氨酸清除调控的不同生化反应，以及叶酸缺乏对同型半胱氨酸代谢的各种影响。
