Enzymology of Pyrimidine Metabolism and Neurodegeneration
Enzymology of Pyrimidine Metabolism and Neurodegeneration
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DOI：
10.2174/0929867323666160411125803
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发表时间：
2016-01-01
影响因子：
4.1
通讯作者：
Pucciarelli, Stefania
中科院分区：
文献类型：
--
作者：
Vincenzetti, Silvia;Polzonetti, Valeria;Pucciarelli, Stefania
众所周知，嘧啶途径的紊乱可能导致神经、血液、免疫疾病、肾损伤以及与恶性肿瘤的相关性。核苷酸稳态取决于嘧啶代谢的三个阶段：这些代谢物的从头合成、分解代谢和再循环。胞苷和尿苷除了用作嘧啶核苷酸回收的底物外，还充当三磷酸胞苷的前体，用于通过肯尼迪循环进行脑磷脂酰胆碱和磷脂酰乙醇胺的生物合成途径。除了葡萄糖之外，大脑中磷脂酰胆碱和其他膜磷脂的合成还可以利用血流中存在的三种化合物：胆碱、尿苷和二十二碳六烯酸等多不饱和脂肪酸。一些作者使用大鼠模型发现，口服两种磷脂前体（例如尿苷和 omega-3 脂肪酸）以及饮食中的胆碱，可以增加存活纹状体生成的突触膜的量。诱发帕金森病的大鼠的神经元。其他作者发现，在喂食尿苷和胆碱的高血压大鼠中，认知缺陷得到改善。尿苷最近也被认为是一种神经活性分子，因为它通过改善记忆、睡眠障碍、抗癫痫作用以及神经元可塑性来参与重要的神经功能。胞苷和尿苷通过特定受体被大脑吸收，并相继被回收为相应的核苷酸。本综述致力于嘧啶途径的酶学，其重要性引起了几位研究大脑病理生理学机制的研究人员的注意。
It is well known that disorders of pyrimidine pathways may lead to neurological, hematological, immunological diseases, renal impairments, and association with malignancies. Nucleotide homeostasis depends on the three stages of pyrimidine metabolism: de novo synthesis, catabolism and recycling of these metabolites.Cytidine and uridine, in addition to be used as substrates for pyrimidine nucleotide salvaging, also act as the precursors of cytidine triphosphate used in the biosynthetic pathway of both brain's phosphatidylcholine and phosphatidylethanolamine via the Kennedy cycle. The synthesis in the brain of phosphatidylcholine and other membrane phosphatides can utilize, in addition to glucose, three compounds present in the blood stream: choline, uridine, and a polyunsaturated fatty acids like docosahexaenoic acid.Some authors, using rat models, found that oral administration of two phospholipid precursors such as uridine and omega-3 fatty acids, along with choline from the diet, can increase the amount of synaptic membrane generated by surviving striatal neurons in rats with induced Parkinson's disease. Other authors found that in hypertensive rat fed with uridine and choline, cognitive deficit resulted improved. Uridine has also been recently considered as a neuroactive molecule, because of its involvement in important neurological functions by improving memory, sleep disorders, anti-epileptic effects, as well as neuronal plasticity. Cytidine and uridine are uptaken by the brain via specific receptors and successively salvaged to the corresponding nucleotides. The present review is devoted to the enzymology of pyrimidine pathways whose importance has attracted the attention of several researchers investigating on the mechanisms underlying the physiopathology of brain.