Title:Enzymology of Pyrimidine Metabolism and Neurodegeneration
Volume: 23
Issue: 14
Author(s): Silvia Vincenzetti, Valeria Polzonetti, Daniela Micozzi, Stefania Pucciarelli
Affiliation:
关键词:
嘧啶打捞，“de novo”嘧啶，嘧啶代谢酶，嘧啶动态平衡，核苷转运，脑磷脂的合成，神经系统疾病。
摘要: 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.
