Bottiglieri T, Hyland K, Reynolds E H
Metabolic Disease Center, Baylor Research Institute, Dallas, Texas.
Drugs. 1994 Aug;48(2):137-52. doi: 10.2165/00003495-199448020-00002.
This review focuses on the biochemical and clinical aspects of methylation in neuropsychiatric disorders and the clinical potential of their treatment with ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.
本综述聚焦于神经精神疾病中甲基化的生化及临床方面，以及用腺苷蛋氨酸（S-腺苷甲硫氨酸；SAMe）进行治疗的临床潜力。SAMe参与众多涉及核酸、蛋白质、磷脂、胺类及其他神经递质的转甲基反应。SAMe的合成与叶酸及维生素B12（氰钴胺）代谢密切相关，已发现这两种维生素的缺乏均会降低中枢神经系统SAMe浓度。叶酸和维生素B12缺乏均可导致类似的神经和精神障碍，包括抑郁、痴呆、脊髓病和周围神经病变。SAMe在中枢神经系统具有多种药理作用，尤其是对单胺神经递质代谢和受体系统。SAMe具有抗抑郁特性，初步研究表明它可能改善痴呆患者的认知功能。用甲基供体（甜菜碱、蛋氨酸和SAMe）进行治疗与叶酸和C-1（一碳）代谢先天性缺陷患者的髓鞘再生有关。这些研究支持了当前的一种理论，即在几种神经和精神疾病中，甲基化受损可能通过不同机制发生。
