Overview
Uridine is one of the key nucleotide that making RNA
[1-3]. It is a glycosylated pyrimidine-analog containing uracil attached to a ribose ring[or more specifically, a ribofuranose] via a β-N1-glycosidic bond. It is one of the five standard nucleosides which make up nucleic acids[including both RNA and DNA] with the others four being adenosine, thymidine, cytidine and guanosine. The five nucleosides are commonly abbreviated to their one-letter codes U, A, T, C and G respectively. Thymidine is found in deoxyribonucleic acid[DNA] and not ribonucleic acid(RNA]. Conversely, uridine is found in RNA and not DNA
[1, 3]. The remaining three nucleosides can be found in both RNA and DNA. In RNA, they would be represented as A, C and G whereas in DNA they would be represented as dA, dC and dG
[1,3].
Biosynthesis and source
Uridine is widely produced in the form of uridine monophosphate[uridylate] through the decarboxylation of orotidylate, being catalyzed by orotidylate decarboxylase
[4]. The orotidylate is produced from orotate, which is combined with 5-phosphoribosyl-1-pyrophosphate[PRPP] to form orotidylate by pyrimidine phosphoribosyltransferase. PRPP is created from ribose-5-phosphate by a further phosphorylation, serving as an energetic molecule to drive the reaction forward, while orotate is generated in several steps from carbamoyl phosphate and aspartate
[4].
Diet is not an important source of uridine. Clinical studies and animal experimentation suggest that the
liver synthesizes and degrades uridine, and is likely to have a central role in maintaining plasma uridine. Blood platelets and storage organelles of various species are reported to contain UTP and may provide releasable pools of uridine after catabolism
[5].
Applications
Uridine is phosphorylated to nucleotides, which are used for DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation
[6-8]. Uridine plays a very important role in the glycolysis pathway of galactose. It can be used as a precursor in the production of CDP-choline. It is an important nutrient and widely used as a dietary supplement. It can improve the brain cholinergic functions and hepatic mitochondrial function in certain liver toxins. It plays a major role in pain physiology and brain energy utilization to maintain ATP production under restricted oxygen conditions
[6, 8]. Uridine has many biological effects and, is thus can be used for the treatment of various kinds of diseases. In general, uridine can be used for the treatment for the following diseases such as cardiovascular disease and hypertension, respiratory dysfunction, liver disease, infertility, epilepsy, cancer & AIDS, Parkinsonism, anxiety, sleep dysfunction and Ischemia and hypoxia
[7,8].
Effect on the central nerve system
Uridine plays a crucial role in the pyrimidine metabolism of the brain. It supplies nervous tissue with the pyrimidine ring, and in turn, participates in a number of important metabolic pathways. Uridine and its nucleotide derivatives may also have an additional role in the function of the central nervous system as signaling molecules. Uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Uridine can exert various kinds of effects on the central nerve system[CNS]
[1, 8-10] It was found to be an active component of sleep-promoting substances in our brain
[11, 12, 2] Anti-epileptogenic and anti-convulsant effect
[3, 9, 10] Thermoregulatory effect
[4, 13] long-term exposure to uridine improve our memory
[5, 14] involved in the regulation of neuronal plasticity through for example that it enhances neurite outgrowth
[15]. Based on those above findings, it can be used for the treatment of various diseases such as developmental delay, seizures, ataxia, severe language deficit, age-related cognitive decline and even Alzheimer's disease and Parkinson's disease. Uridine might also be useful as a nutrition supplement during development. Uridine[as uridine monophosphate] is found in mother's milk and has been proposed to play a role in regulatory mechanism through which plasma composition influences brain development
[16].
Cystic fibrosis
Cystic fibrosis is characterized by abnormal fluid transport across many epithelia including airways, pancreas, sweat glands and small intestine. This disease is associated with decreased Cl2 transport
and increased Na+ transport. The disease is caused by an absence or dysfunction of the cystic fibrosis transmembrane conductance regulator[CFTR], a Clchannel expressed by epithelial cells, and by an increase in active Na+ absorption[17, 18]. The uridine nucleotide can be used for the treatment of cystic fibrosis since UTP activates P2 purinoceptors, bypasses the defective Clsecretion to activate an alternative Ca2+ -dependent Clsecretory pathway, further stimulating Clsecretion in epithelial cells and decreased Na+ absorption
[18].
Effects on the circulatory system
The effects of uridine and its nucleotides on isolated blood vessels are complex, sometimes acting directly on smooth muscle cells, at other times stimulating surrounding endothelial cells. Uridine and its nucleotides produce opposing effects in some tissues, which suggests that these ligands could act at distinct receptors or via intracellular messenger systems. Further studies are warranted, because many of these effects were observed at potentially physiological levels, and could aid the development of a novel series of antihypertensive agents based on uridine analogues
[19].
Modulation of reproduction
An important function of uridine could be to promote sperm motility, as seminal plasma uridine concentrations are positively correlated to percentage sperm motility
[20]. It is perhaps relevant, therefore, that regulation of uridine diphosphatase during spermatogenesis in the rat was reported to be under hormonal control. The predominance of uridine in seminal fluids must lead to questions about its role in the environment of fertilization and implantation, but as yet these remain unanswered
[21].
Cancer and antiviral therapy
Uridine and UDP‹glucose have been used to counter the unwanted toxicity of pyrimidine-based anticancer drugs. Uridine has been used as a rescue therapy for myelotoxicity and gastrointestinal toxicity produced by 5-fluorouracil
[22]. Uridine and benzylacyclouridine protected mice against the neurotoxic side effects of pyrimidine-based drugs, such as azidothymidine used to treat HIV infection
[23].
