General Information of MET (ID: META00241)
Name Uridine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
1-b-D-Ribofuranosyl-2,4(1H,3H)-pyrimidinedione; 1-beta-D-Ribofuranosylpyrimidine-2,4(1H,3H)-dione; 1-beta-D-Ribofuranosyluracil; 1-beta-delta-Ribofuranosyl-2,4(1H,3H)-pyrimidinedione; 1-beta-delta-Ribofuranosyluracil; Allo uridine; Allo-uridine; Allouridine; Urd; Uridin; b-D-Ribofuranoside 2,4(1H,3H)-pyrimidinedione-1; beta-Uridine; beta-delta-Ribofuranoside 2,4(1H,3H)-pyrimidinedione-1; u
Source Endogenous;Escherichia Coli Metabolite;Yeast Metabolite;Food;Cosmetic;TCM Ingredients;Microbial
Structure Type   Pyrimidine nucleosides  (Click to Show/Hide the Complete Structure Type Hierarchy)
Nucleosides, nucleotides, and analogues
Pyrimidine nucleosides
PubChem CID
6029
HMDB ID
HMDB0000296
Formula
C9H12N2O6
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00299
DrugBank ID
DB02745
ChEBI ID
16704
FooDB ID
FDB007411
ChemSpider ID
5807
METLIN ID
90
Physicochemical Properties Molecular Weight 244.2 Topological Polar Surface Area 119
XlogP -2 Complexity 371
Heavy Atom Count 17 Rotatable Bond Count 2
Hydrogen Bond Donor Count 4 Hydrogen Bond Acceptor Count 6
Function
Uridine, also known as beta-uridine or 1-beta-D-ribofuranosylpyrimidine-2,4(1H,3H)-dione, is a member of the class of compounds known as pyrimidine nucleosides. Pyrimidine nucleosides are compounds comprising a pyrimidine base attached to a ribosyl or deoxyribosyl moiety. More specifically, uridine is a nucleoside consisting of uracil and D-ribose and a component of RNA. Uridine is soluble (in water) and a very weakly acidic compound (based on its pKa). Uridine can be synthesized from uracil. It is one of the five standard nucleosides which make up nucleic acids, the others being adenosine, thymidine, cytidine and guanosine. The five nucleosides are commonly abbreviated to their one-letter codes U, A, T, C and G respectively. Uridine is also a parent compound for other transformation products, including but not limited to, nikkomycin Z, 3'-(enolpyruvyl)uridine 5'-monophosphate, and 5-aminomethyl-2-thiouridine. Uridine can be found in most biofluids, including urine, breast milk, cerebrospinal fluid (CSF), and blood. Within the cell, uridine is primarily located in the mitochondria, in the nucleus and the lysosome. It can also be found in the extracellular space. As an essential nucleoside, uridine exists in all living species, ranging from bacteria to humans. In humans, uridine is involved in several metabolic disorders, some of which include dhydropyrimidinase deficiency, MNGIE (mitochondrial neurogastrointestinal encephalopathy), and beta-ureidopropionase deficiency. Moreover, uridine is found to be associated with Lesch-Nyhan syndrome, which is an inborn error of metabolism. Uridine is a nucleoside consisting of uracil and D-ribose and a component of RNA. Uridine plays a role in the glycolysis pathway of galactose. In humans there is no catabolic process to metabolize galactose. Therefore, galactose is converted to glucose and metabolized via the normal glucose metabolism pathways. More specifically, consumed galactose is converted into galactose 1-phosphate (Gal-1-P). This molecule is a substrate for the enzyme galactose-1-phosphate uridyl transferase which transfers a UDP molecule to the galactose molecule. The end result is UDP-galactose and glucose-1-phosphate. This process is continued to allow the proper glycolysis of galactose. Uridine is found in many foods (anything containing RNA) but is destroyed in the liver and gastrointestinal tract, and so no food, when consumed, has ever been reliably shown to elevate blood uridine levels. On the other hand, consumption of RNA-rich foods may lead to high levels of purines (adenine and guanosine) in blood. High levels of purines are known to increase uric acid production and may aggravate or lead to conditions such as gout.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Apolipoprotein (Apo)
            Apolipoprotein A-II (APOA2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (-265T >C(rs5082)) of APOA2
                      Induced Change Uridine concentration: increase (FC = 1.13)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Obesity [ICD-11: 5B81]
                      Details It is reported that mutation (-265T >C(rs5082)) of APOA2 leads to the increase of uridine levels compared with control group.
      Equilibrative nucleoside transporter (ENT)
            Equilibrative nucleoside transporter 2 (SLC29A2) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Inhibition (Nitrobenzylthioinosine (NBMPR)) of SLC29A2
                      Induced Change Uridine concentration: decrease (FC = 0.15)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC29A2 leads to the decrease of uridine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Overexpression of SLC29A2
                      Induced Change Uridine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC29A2 leads to the increase of uridine levels compared with control group.
      GPCR secretin (GPCR-2)
            Glucagon receptor (GCGR) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockout of Gcgr
                      Induced Change Uridine concentration: increase (FC = 1.7)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Type 2 diabetes mellitus [ICD-11: 5A11]
                      Details It is reported that knockout of GCGR leads to the increase of uridine levels compared with control group.
      Hydrolases (EC 3)
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Uridine concentration: decrease (FC = 0.68 / 0.82)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the decrease of uridine levels compared with control group.
      Lyases (EC 4)
            Cystathionine gamma-lyase (CTH) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Knockout of Cth
                      Induced Change Uridine concentration: increase (FC = 2.61)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Organic acid disorderss [ICD-11: 5C50]
                      Details It is reported that knockout of Cth leads to the increase of uridine levels compared with control group.
      Nitrogen permease regulator (NPR)
            Natriuretic peptide receptor B (NPR2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Deletion of NPR2
                      Induced Change Uridine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that deletion of NPR2 leads to the increase of uridine levels compared with control group.
      Pore-forming PNC peptide (PNC)
            Cellular tumor antigen p53 (TP53) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Knockout of TP53
                      Induced Change Uridine concentration: increase (Log2 FC=1.28)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockout of TP53 leads to the increase of uridine levels compared with control group.
      Transferases (EC 2)
            Pyridoxal kinase (PDXK) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Knockout (CRISPR/Cas9 sgRNA) of PDXK
                      Induced Change Uridine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute myeloid leukaemia [ICD-11: 2A60]
                      Details It is reported that knockout of PDXK leads to the decrease of uridine levels compared with control group.
References
1 Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity. Am J Clin Nutr. 2018 Jul 1;108(1):188-200.
2 Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem J. 1997 Dec 15;328 ( Pt 3)(Pt 3):739-43.
3 Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes. BMC Genomics. 2011 Jun 1;12:281.
4 Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab. 2014 Nov 4;2:24.
5 Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes. Oxid Med Cell Longev. 2021 Feb 13;2021:8877691.
6 Npr2 inhibits TORC1 to prevent inappropriate utilization of glutamine for biosynthesis of nitrogen-containing metabolites. Sci Signal. 2014 Dec 16;7(356):ra120.
7 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.
8 Vitamin B6 Addiction in Acute Myeloid Leukemia. Cancer Cell. 2020 Jan 13;37(1):71-84.e7.

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