Uridine and its nucleotides: biological actions, therapeutic potentials

Connolly, G.P.; Duley, John A.

doi:10.1016/s0165-6147(99)01298-5

Cited by 176 publications

(131 citation statements)

References 49 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Through the uridine salvage pathway, uridine can be converted to UMP and then to other pyrimidine nucleotides, including CMP, dCMP, and TMP (4,10,18). In UPaseϪ/Ϫ mice, therefore, we have detected significant elevations in the concentrations of various pyrimidine nucleotides, including total uridine ribonucleotide, total cytidine ribonucleotide, dCTP, and dTTP.…”

Section: Discussionmentioning

confidence: 85%

Abnormalities in Uridine Homeostatic Regulation and Pyrimidine Nucleotide Metabolism as a Consequence of the Deletion of the Uridine Phosphorylase Gene

Cao

Leffert

McCabe

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

We report in the present study the critical role of uridine phosphorylase (UPase) in uridine homeostatic regulation and pyrimidine nucleotide metabolism, employing newly developed UPase؊/؊ mice. Our data demonstrate that the abrogation of UPase activity led to greater than a 6-fold increase in uridine concentrations in plasma, a 5-6-fold increase in lung and gut, and a 2-3-fold increase in liver and kidney, as compared with wild type mice. Urine uridine levels increased 24-fold normal in UPase؊/؊ mice. Uridine half-life and the plasma retention of pharmacological doses of uridine were significantly prolonged. Further, in these UPase؊/؊ mice, abnormal uridine metabolism led to disorders of various nucleotide metabolisms. In the liver, gut, kidney, and lung of UPase؊/؊ mice, total uridine ribonucleotide concentrations increased 2-3 times as compared with control mice. Cytidine ribonucleotides and adenosine and guanosine ribonucleotides also increased, although to a lesser extent, in these organs. Most significant deoxyribonucleotide changes were present in the gut and lung of UPase؊/؊ mice. In these tissues, dTTP concentration increased more than 4-fold normal, and dCTP, dGTP, and dATP concentrations rose 1-2 times normal. In kidney, dTTP concentration increased 2-fold normal, and dCTP and dGTP concentrations rose less than 1-fold normal. In addition, the accumulated uridine in plasma and tissues efficiently reduced 5-fluorouracil host toxicity and altered the anesthetic effect of pentobarbital. These data indicate that UPase is a critical enzyme in the regulation of uridine homeostasis and pyrimidine nucleotide metabolism, and 5-fluorouracil activity.

show abstract

Section: Discussionmentioning

confidence: 85%

Abnormalities in Uridine Homeostatic Regulation and Pyrimidine Nucleotide Metabolism as a Consequence of the Deletion of the Uridine Phosphorylase Gene

Cao

Leffert

McCabe

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…These bases can enter the enterocytes via nucleobase transporters and be salvaged by the action of hypoxanthine-guanine phosphorybosiltransferase (1,2). Uridine is known to be rapidly absorbed and incorporated to the cellular nucleotide pool by the action of uridine kinase (29). The concentrations of adenosine were dependent on the RNA concentration in the culture medium and increased over the first 2 hours of incubation but decreased afterward, parallel to the increase in inosine.…”

Section: Discussionmentioning

confidence: 99%

Ribonucleic Acid Hydrolysis by Intestinal Explants of Neonatal Piglets

Rueda¹,

Gómez-León²,

Gil³

2002

Journal of Pediatric Gastroenterology and Nutrition

View full text Add to dashboard Cite

Background: Healthy human adults are able to hydrolyze dietary nucleic acids and nucleotides in the gastrointestinal tract, thus facilitating absorption of the resulting nucleosides. However, little is directly known of the ability of infants to hydrolyze nucleic acids early in life. Methods: Purified RNA (50, 100, 250, and 500 mg/L) in a suitable medium was exposed to jejunal explants of weaning piglets to determine if enzymes expressed by the explants were sufficient to hydrolyze the nucleic acid. Aliquots from the media were taken at time intervals, from 0 to 6 hours, and assayed for ribonucleoside content by high-performance liquid chromatography. Results: The investigators found a significant increase of free ribonucleosides during the study period and for all RNA concentrations tested, thus suggesting that intestinal explants are able to hydrolyze RNA. The kinetics of nucleoside concentrations varied for each nucleoside. For example, inosine increased over the entire 6-hour period and adenosine increased for the first 2 hours, decreasing afterward. Conclusions: It is concluded that cells from the intestinal epithelium are capable of hydrolyzing RNA. These results suggest that RNA present in human milk is hydrolyzed in the intestinal tract of the breast-fed infant, thus providing an additional source of nucleosides. The results indicate that current supplementation of infant formulas with nucleotides should be reconsidered to take into account the contribution of RNA present in human milk to the pool of bioavailable nucleotides. JPGN 35:685-690, 2002.

show abstract

“…However, UTP was ineffective in 4-aminopyridine (4-AP)-induced epileptiform activity [140]. Uridine has already been tested in human studies [360][361][362][363][364], and a decrease in seizure activity in response to Urd has been demonstrated in humans [363][364][365]. Uridine is also found in mother's milk and may be useful as a nutritional supplement during early postnatal development [366,367]; consequently, Urd is a well tolerable drug, which showed low toxicity [63,64,360,361].…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

View full text Add to dashboard Cite

Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

show abstract

Uridine and its nucleotides: biological actions, therapeutic potentials

Cited by 176 publications

References 49 publications

Abnormalities in Uridine Homeostatic Regulation and Pyrimidine Nucleotide Metabolism as a Consequence of the Deletion of the Uridine Phosphorylase Gene

Abnormalities in Uridine Homeostatic Regulation and Pyrimidine Nucleotide Metabolism as a Consequence of the Deletion of the Uridine Phosphorylase Gene

Ribonucleic Acid Hydrolysis by Intestinal Explants of Neonatal Piglets

The Antiepileptic Potential of Nucleosides

Contact Info

Product

Resources

About