Showing metabocard for Orotic acid (MMDBc0000076)

Record Information
Version1.0
StatusDetected and Quantified
Creation Date2020-10-27 23:29:30 UTC
Update Date2024-09-29 15:02:32 UTC
Metabolite IDMMDBc0000076
Metabolite Identification
Common NameOrotic acid
DescriptionOrotic acid is a minor dietary constituent. Indeed, until it was realized that it could be synthesized by humans, orotic acid was known as vitamin B-13. The richest dietary sources of orotic acid are cow's milk and other dairy products as well as root vegetables such as carrots and beets. Dietary intake probably contributes to a basal rate of orotic acid excretion in urine because fasting decreases excretion by ~50%. However, it is now apparent that most urinary orotic acid is synthesized in the body, where it arises as an intermediate in the pathway for the synthesis of pyrimidine nucleotides. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotate phosphoribosyltransferase and orotidylate decarboxylase activity. The most frequently observed inborn error of pyrimidine nucleotide synthesis is a mutation of the multifunctional protein UMP synthase (UMP synthase deficiency or orotic aciduria). This disorder prevents the conversion of orotic acid to UMP, and thus to other pyrimidines. As a result, plasma orotic acid accumulates to high concentrations, and increased quantities appear in the urine. Indeed, urinary orotic acid is so markedly increased in individuals harboring a mutation in UMP synthase that orotic acid crystals can form in the urine. The urinary concentration of orotic acid in individuals suffering from orotic aciduria can be of the order of millimoles per millimole creatinine. By comparison, the urinary level in unaffected individuals is ~ 1 µmol/mmol creatinine (PMID: 17513443 ). Orotic aciduria is characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy and most cases appear to have a good prognosis. When present in sufficiently high levels, orotic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of orotic acid are associated with at least seven inborn errors of metabolism, including argininemia, LPI syndrome (lysinuric protein intolerance), hyperornithinemia-hyperammonemia-homocitrullinuria (HHH), OTC deficiency, citrullinemia type I, purine nucleoside phosphorylase deficiency, and orotic aciduria. Orotic acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.
Structure
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for #<Metabolite:0x00007f9238dab160>


  Mrv1652309032023582D          

 11 11  0  0  0  0            999 V2000
    2.8579    0.0000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -1.2375    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7145   -0.4125    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    0.8250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145    1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145    2.0625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289    0.8250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  2  3  2  0  0  0  0
  2  4  1  0  0  0  0
  4  5  2  0  0  0  0
  5  6  1  0  0  0  0
  6  7  2  0  0  0  0
  6  8  1  0  0  0  0
  8  9  1  0  0  0  0
  9 10  2  0  0  0  0
  9 11  1  0  0  0  0
  4 11  1  0  0  0  0
M  END
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3D MOL for #<Metabolite:0x00007f9238dab160>

HMDB0000226
     RDKit          3D
Orotic acid
 15 15  0  0  0  0  0  0  0  0999 V2000
    2.5704    1.0982    1.0617 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.0502    0.1371    0.4392 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8887   -0.8593   -0.0025 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.6054    0.1169    0.2143 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2148    1.1169    0.6608 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5768    1.0640    0.4295 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3373    1.9676    0.8301 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0609    0.0091   -0.2408 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2428   -0.9730   -0.6775 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7246   -1.9599   -1.3089 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0748   -0.9229   -0.4544 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.1523   -1.0406   -0.9439 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.1786    1.9519    1.1929 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0866   -0.0189   -0.4083 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7233   -1.6872   -0.7924 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  6  8  1  0
  8  9  1  0
  9 10  2  0
  9 11  1  0
 11  4  1  0
  3 12  1  0
  5 13  1  0
  8 14  1  0
 11 15  1  0
M  END
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3D SDF for #<Metabolite:0x00007f9238dab160>


  Mrv1652309032023582D          

 11 11  0  0  0  0            999 V2000
    2.8579    0.0000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -1.2375    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7145   -0.4125    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    0.8250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145    1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145    2.0625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289    0.8250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  2  3  2  0  0  0  0
  2  4  1  0  0  0  0
  4  5  2  0  0  0  0
  5  6  1  0  0  0  0
  6  7  2  0  0  0  0
  6  8  1  0  0  0  0
  8  9  1  0  0  0  0
  9 10  2  0  0  0  0
  9 11  1  0  0  0  0
  4 11  1  0  0  0  0
M  END
> <DATABASE_ID>
MMDBc0000076

> <DATABASE_NAME>
MIME

> <SMILES>
OC(=O)C1=CC(=O)NC(=O)N1

> <INCHI_IDENTIFIER>
InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)

> <INCHI_KEY>
PXQPEWDEAKTCGB-UHFFFAOYSA-N

> <FORMULA>
C5H4N2O4

> <MOLECULAR_WEIGHT>
156.0963

> <EXACT_MASS>
156.017106626

> <JCHEM_ACCEPTOR_COUNT>
4

> <JCHEM_ATOM_COUNT>
15

> <JCHEM_AVERAGE_POLARIZABILITY>
12.461507679606417

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
3

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid

> <ALOGPS_LOGP>
-0.89

> <JCHEM_LOGP>
-1.227664501

> <ALOGPS_LOGS>
-1.54

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
1

> <JCHEM_PHYSIOLOGICAL_CHARGE>
-1

> <JCHEM_PKA>
8.781577888084735

> <JCHEM_PKA_STRONGEST_ACIDIC>
2.827266331449678

> <JCHEM_PKA_STRONGEST_BASIC>
-6.031557162374663

> <JCHEM_POLAR_SURFACE_AREA>
95.5

> <JCHEM_REFRACTIVITY>
33.27460000000001

> <JCHEM_ROTATABLE_BOND_COUNT>
1

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
4.51e+00 g/l

> <JCHEM_TRADITIONAL_IUPAC>
orotic acid

> <JCHEM_VEBER_RULE>
0

$$$$
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3D-SDF for #<Metabolite:0x00007f9238dab160>

HMDB0000226
     RDKit          3D
Orotic acid
 15 15  0  0  0  0  0  0  0  0999 V2000
    2.5704    1.0982    1.0617 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.0502    0.1371    0.4392 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8887   -0.8593   -0.0025 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.6054    0.1169    0.2143 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2148    1.1169    0.6608 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5768    1.0640    0.4295 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3373    1.9676    0.8301 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0609    0.0091   -0.2408 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2428   -0.9730   -0.6775 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7246   -1.9599   -1.3089 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0748   -0.9229   -0.4544 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.1523   -1.0406   -0.9439 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.1786    1.9519    1.1929 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0866   -0.0189   -0.4083 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7233   -1.6872   -0.7924 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  6  8  1  0
  8  9  1  0
  9 10  2  0
  9 11  1  0
 11  4  1  0
  3 12  1  0
  5 13  1  0
  8 14  1  0
 11 15  1  0
M  END
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PDB for #<Metabolite:0x00007f9238dab160>

HEADER    PROTEIN                                 03-SEP-20   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   03-SEP-20         0                                  
HETATM    1  O   UNK     0       5.335   0.000   0.000  0.00  0.00           O+0
HETATM    2  C   UNK     0       4.001  -0.770   0.000  0.00  0.00           C+0
HETATM    3  O   UNK     0       4.001  -2.310   0.000  0.00  0.00           O+0
HETATM    4  C   UNK     0       2.667   0.000   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0       1.334  -0.770   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0       0.000   0.000   0.000  0.00  0.00           C+0
HETATM    7  O   UNK     0      -1.334  -0.770   0.000  0.00  0.00           O+0
HETATM    8  N   UNK     0       0.000   1.540   0.000  0.00  0.00           N+0
HETATM    9  C   UNK     0       1.334   2.310   0.000  0.00  0.00           C+0
HETATM   10  O   UNK     0       1.334   3.850   0.000  0.00  0.00           O+0
HETATM   11  N   UNK     0       2.667   1.540   0.000  0.00  0.00           N+0
CONECT    1    2                                                            
CONECT    2    1    3    4                                                  
CONECT    3    2                                                            
CONECT    4    2    5   11                                                  
CONECT    5    4    6                                                       
CONECT    6    5    7    8                                                  
CONECT    7    6                                                            
CONECT    8    6    9                                                       
CONECT    9    8   10   11                                                  
CONECT   10    9                                                            
CONECT   11    9    4                                                       
MASTER        0    0    0    0    0    0    0    0   11    0   22    0
END
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3D PDB for #<Metabolite:0x00007f9238dab160>

COMPND    HMDB0000226
HETATM    1  O1  UNL     1       2.570   1.098   1.062  1.00  0.00           O  
HETATM    2  C1  UNL     1       2.050   0.137   0.439  1.00  0.00           C  
HETATM    3  O2  UNL     1       2.889  -0.859  -0.003  1.00  0.00           O  
HETATM    4  C2  UNL     1       0.605   0.117   0.214  1.00  0.00           C  
HETATM    5  C3  UNL     1      -0.215   1.117   0.661  1.00  0.00           C  
HETATM    6  C4  UNL     1      -1.577   1.064   0.430  1.00  0.00           C  
HETATM    7  O3  UNL     1      -2.337   1.968   0.830  1.00  0.00           O  
HETATM    8  N1  UNL     1      -2.061   0.009  -0.241  1.00  0.00           N  
HETATM    9  C5  UNL     1      -1.243  -0.973  -0.677  1.00  0.00           C  
HETATM   10  O4  UNL     1      -1.725  -1.960  -1.309  1.00  0.00           O  
HETATM   11  N2  UNL     1       0.075  -0.923  -0.454  1.00  0.00           N  
HETATM   12  H1  UNL     1       3.152  -1.041  -0.944  1.00  0.00           H  
HETATM   13  H2  UNL     1       0.179   1.952   1.193  1.00  0.00           H  
HETATM   14  H3  UNL     1      -3.087  -0.019  -0.408  1.00  0.00           H  
HETATM   15  H4  UNL     1       0.723  -1.687  -0.792  1.00  0.00           H  
CONECT    1    2    2
CONECT    2    3    4
CONECT    3   12
CONECT    4    5    5   11
CONECT    5    6   13
CONECT    6    7    7    8
CONECT    8    9   14
CONECT    9   10   10   11
CONECT   11   15
END
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SMILES for #<Metabolite:0x00007f9238dab160>

OC(=O)C1=CC(=O)NC(=O)N1
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INCHI for #<Metabolite:0x00007f9238dab160>

InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)
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Synonyms
ValueSource
OrotsaeureChEBI
Uracil-6-carboxylic acidChEBI
Uracil-6-carboxylateGenerator
OrotateGenerator
1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylic acidHMDB
1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acidHMDB
1,2,3,6-Tetrahydro-2,6-dioxopyrimidin-4-carbonsaeureHMDB
2,6-Dihydroxy-4-pyrimidinecarboxylic acidHMDB
2,6-Dihydroxypyrimidine-4-carboxylic acidHMDB
2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acidHMDB
2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acidHMDB
6-Carboxy-2,4-dihydroxypyrimidineHMDB
6-CarboxyuracilHMDB
6-Uracilcarboxylic acidHMDB
Acide orotiqueHMDB
Acido oroticoHMDB
Acidum oroticumHMDB
Animal galactose factorHMDB
LactiniumHMDB
MolkensaeureHMDB
OROHMDB
OrodinHMDB
OropurHMDB
OrotoninHMDB
OrotonsanHMDB
OrotsaureHMDB
OroturicHMDB
OrotylHMDB
Uracil-6-carbosaeureHMDB
Vitamin b13HMDB
Whey factorHMDB
Zinc orotateHMDB
Orotate, zincHMDB
Acid, oroticHMDB
Orotate, potassiumHMDB
Potassium orotateHMDB
Orotate, sodiumHMDB
Sodium orotateHMDB
Molecular FormulaC5H4N2O4
Average Mass156.0963
Monoisotopic Mass156.017106626
IUPAC Name2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid
Traditional Nameorotic acid
CAS Registry Number65-86-1
SMILES
OC(=O)C1=CC(=O)NC(=O)N1
InChI Identifier
InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)
InChI KeyPXQPEWDEAKTCGB-UHFFFAOYSA-N