Vincenzetti Silvia, Polzonetti Valeria, Micozzi Daniela, Pucciarelli Stefania
School of Bioscience and Veterinary Medicine, University of Camerino, Camerino (MC), Italy.
Curr Med Chem. 2016;23(14):1408-31. doi: 10.2174/0929867323666160411125803.
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.
众所周知，嘧啶代谢途径紊乱可能导致神经、血液、免疫疾病、肾脏损害以及与恶性肿瘤相关。核苷酸稳态取决于嘧啶代谢的三个阶段：从头合成、这些代谢物的分解代谢和再循环。胞苷和尿苷除了用作嘧啶核苷酸补救的底物外，还通过肯尼迪循环作为脑磷脂酰胆碱和磷脂酰乙醇胺生物合成途径中使用的三磷酸胞苷的前体。除葡萄糖外，脑内磷脂酰胆碱和其他膜磷脂的合成还可利用血液中存在的三种化合物：胆碱、尿苷和一种多不饱和脂肪酸，如二十二碳六烯酸。一些作者利用大鼠模型发现，口服两种磷脂前体，如尿苷和ω-3脂肪酸，以及饮食中的胆碱，可以增加患有帕金森病的大鼠纹状体存活神经元产生的突触膜数量。其他作者发现，给高血压大鼠喂食尿苷和胆碱后，认知缺陷得到改善。由于尿苷参与改善记忆、睡眠障碍、抗癫痫作用以及神经元可塑性等重要神经功能，它最近也被认为是一种神经活性分子。胞苷和尿苷通过特定受体被脑摄取，并相继补救为相应的核苷酸。本综述致力于嘧啶代谢途径的酶学，其重要性已引起了几位研究脑生理病理学潜在机制的研究人员的关注。
