Biological Methylation and Drug Design
Biological Methylation and Drug Design
复制标题
生物甲基化与药物设计
DOI：
10.1007/978-1-4612-5012-8
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
P. Ueland
中科院分区：
文献类型：
--
作者：
R. Borchardt;C. Creveling;P. Ueland
本文回顾了迄今为止的工作，表明一碳循环的元素可能涉及精神疾病。我们的研究小组报告了一碳循环（红细胞中）的两种酶甲硫氨酸腺苷转移酶（MAT）和丝氨酸羟甲基转移酶（SHMT）在精神分裂症和抑郁症中活性不足，而在躁狂症中活性过度。这与报道的S-腺苷甲硫氨酸在人体中的抗肿瘤作用相关。另一个研究小组也发现SHMT在精神分裂症患者的血清中活性低下。这种缺陷似乎与磷脂在膜中的分布异常有关，磷脂酰胆碱相对缺乏，磷脂酰丝氨酸相对过量。证据表明，药物似乎并不负责这些结果将提交。综述了脂质和蛋白质转甲基化系统在细胞调控系统中的作用。在许多系统中，脂质转甲基化与受体-最终信使偶联以及跨膜信息传递有关。蛋白质甲基化参与许多细胞系统，包括细菌和白细胞的趋化性、神经递质释放、精子运动和钙调蛋白功能。
This paper reviews the work available to date suggesting that elements of the one-carbon cycle may be involved in psychiatric illnesses. Two enzymes of the one-carbon cycle (in erythrocytes) methionine adenosyltransferase (MAT) and serine hydroxymethyltransferase (SHMT) have been reported by our group to be underactive in schizophrenia and depression and overactive in mania. This correlates with the reported anti-depressant effects of S-adenosylmethionine in humans. SHMT has also been found by another group to be underactive in serum of schizophrenics. This defect appears to be linked to abnormalities in the distribution of phospholipids in the membrane, with a relative deficiency of phosphatidylcholine and a relative excess of phosphatidylserine. Evidence showing that medications do not appear to be responsible for these findings will be presented. A review is then made of the role of transmethylation systems for lipids and proteins in cellular control systems. Lipid transmethylation is related in many systems to receptor-final messenger coupling and so to information transfer across the membrane. Protein methylation is involved in many cellular systems including chemotaxis in bacteria and leucocytes, neurotransmitter release, sperm motility and calmodulin function.