Castro R, Rivera I, Blom H J, Jakobs C, Tavares de Almeida I
Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, Lisbon 1649-003, Portugal.
J Inherit Metab Dis. 2006 Feb;29(1):3-20. doi: 10.1007/s10545-006-0106-5.
Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for atherosclerosis and vascular disease. Homocysteine is a branch-point intermediate of methionine metabolism, which can be further metabolised via two alternative pathways: degraded irreversibly through the transsulphuration pathway or remethylated to methionine by the remethylation pathway. Both pathways are B-vitamin-dependent. Plasma homocysteine concentrations are determined by nongenetic and genetic factors. The metabolism of homocysteine, the role of B vitamins and the contribution of nongenetic and genetic determinants of homocysteine concentrations are reviewed. The mechanisms whereby homocysteine causes endothelial damage and vascular disease are not fully understood. Recently, a link has been postulated between homocysteine, or its intermediates, and an alterated DNA methylation pattern. The involvement of epigenetic mechanisms in the context of homocysteine and atherosclerosis, due to inhibition of transmethylation reactions, is briefly overviewed.
高同型半胱氨酸血症被视为动脉粥样硬化和血管疾病的一种新的可改变风险因素。同型半胱氨酸是甲硫氨酸代谢的一个分支点中间体，它可以通过两条替代途径进一步代谢：通过转硫途径不可逆地降解，或通过再甲基化途径再甲基化为甲硫氨酸。这两条途径均依赖于B族维生素。血浆同型半胱氨酸浓度由非遗传因素和遗传因素决定。本文综述了同型半胱氨酸的代谢、B族维生素的作用以及同型半胱氨酸浓度的非遗传和遗传决定因素的贡献。同型半胱氨酸导致内皮损伤和血管疾病的机制尚未完全明确。最近，有人推测同型半胱氨酸或其中间体与DNA甲基化模式改变之间存在联系。本文简要概述了由于转甲基反应受到抑制，表观遗传机制在同型半胱氨酸与动脉粥样硬化关系中的作用。
