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{{Short description|Chemical compound synthesized in the body via a mitochondrial enzyme}} |
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{{Citations missing|date=October 2007}} |
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{{Drugbox |
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| Verifiedfields = changed |
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{{drugbox |
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| Watchedfields = changed |
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| verifiedrevid = 265738220 |
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| verifiedrevid = 388986736 |
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| IUPAC_name = 1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid |
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| IUPAC_name = 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid |
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| image = Orotic-acid-2D-skeletal.png |
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| image = Orotic acid.svg |
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| width = 150px |
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| width = 150px |
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<!--Clinical data--> |
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| tradename = |
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| Drugs.com = {{drugs.com|international|orotic-acid}} |
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| pregnancy_category = |
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| legal_status = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| elimination_half-life = |
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<!--Identifiers--> |
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| IUPHAR_ligand = 4690 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 65-86-1 |
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| CAS_number = 65-86-1 |
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| CASNo_Ref = {{cascite}} |
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| ATC_prefix = none |
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| ATC_prefix = none |
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| ATC_suffix = |
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| ATC_suffix = |
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| ATC_supplemental = |
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| ATC_supplemental = |
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| PubChem = 967 |
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| PubChem = 967 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = EXPT02447 |
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| DrugBank = DB02262 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = 61H4T033E5 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = C00295 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 942 |
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| smiles = O=C(O)\C1=C\C(=O)NC(=O)N1 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 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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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = PXQPEWDEAKTCGB-UHFFFAOYSA-N |
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| synonyms = uracil-6-carboxylic acid |
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<!--Chemical data--> |
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| C=5 | H=4 | N=2 | O=4 |
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| C=5 | H=4 | N=2 | O=4 |
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| molecular_weight = 156.10 g/mol |
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| bioavailability = |
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'''Orotic acid''' is a ] and an ]; it is also known as '''pyrimidinecarboxylic acid'''. It was once believed to be part of the ] complex and was called '''vitamin B<sub>13</sub>''', but it is now known that it is not a ] but is instead manufactured in the body by ].<ref name="">{{cite web |title=Vitamin B13 (Orotic Acid) |url=http://www.dietandfitnesstoday.com/vitaminB13.php }}</ref><ref name="Husebye">{{cite journal |author=Husebye E, Skar V, Høverstad T, Melby K |title=Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people |journal= Gut |volume=33 |issue= |pages=1331–1337 |year=1992 |pmid= |doi=10.1136/gut.33.10.1331 |url=http://gut.bmj.com/content/33/10/1331.abstract }}</ref><ref name="Greenbaum">{{cite journal |author=Greenbaum SB |title=Orotic acid antagonist: "6-Uracilsulfonic Acid, a Sulronic Acid Analog of Orotic Acid |journal=J. Am. Chem. Soc. |volume=76 |issue=23 |pages=6052–6054 |year=1954 |pmid= |doi= |url= }}</ref> |
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'''Orotic acid''' ({{IPAc-en|ɔː|ˈ|r|ɒ|t|ɪ|k}})<ref>{{cite Merriam-Webster|Orotic acid|access-date=2023-02-07}}</ref> is a ] and a ]. Historically, it was believed to be part of the ] complex and was called '''vitamin B<sub>13</sub>''', but it is now known that it is not a ]. |
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Its salts, known as orotates, are sometimes used as mineral carriers in some ], to increase their ]. ] is the most frequently used in this manner. |
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The compound is synthesized in the body via a ]l enzyme, ]<ref>{{cite journal | vauthors = Rawls J, Knecht W, Diekert K, Lill R, Löffler M | title = Requirements for the mitochondrial import and localization of dihydroorotate dehydrogenase | journal = European Journal of Biochemistry | volume = 267 | issue = 7 | pages = 2079–2087 | date = April 2000 | pmid = 10727948 | doi = 10.1046/j.1432-1327.2000.01213.x | doi-access = free }}</ref> or a cytoplasmic enzyme of ]. It is sometimes used as a ] in some ] (to increase their ]), most commonly for ]. |
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==Synthesis of Orotate== |
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Dihydroorotate is synthesized to Orotic Acid by Dihydroorate Dehydrogenase, where it later combines with PRPP (Phosphoribosyl Pyrophosphate) to form ] (OMP). A distinguishing characteristic of pyrimidine synthesis is that the pyrimidine ring is fully synthesized before being attached to the ribose sugar, whereas purine synthesis happens by building the base directly on the sugar.<ref>Lippincott. Biochemistry 4th Edition. 2008</ref> |
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==Orotic acid diseases== |
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== Synthesis == |
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] is synthesized to orotic acid by the ] dihydroorotate dehydrogenase, where it later combines with ] (PRPP) to form ] (OMP). A distinguishing characteristic of ] is that the pyrimidine ring is fully synthesized before being attached to the ], whereas purine synthesis happens by building the base directly on the sugar.<ref>{{cite book | veditors = Harvey D, Ferrier D | publisher= Lippincott, Williams & Wilkins| title= Biochemistry | edition = 5th | date = 2008| page= 302| url= http://www.uobabylon.edu.iq/eprints/paper_11_9137_715.pdf}}</ref> |
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A buildup of orotic acid can lead to ]. It may be a symptom of an increased ] load due to a ], such as a ]. |
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==Chemistry== |
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In ], a disorder of the urea cycle, excess carbamoyl phosphate is converted into orotic acid. This typically leads to increased urinary orotic acid excretion, because the orotic acid is not being properly utilized and must be eliminated. |
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Orotic acid is a ] and its ], the orotate ], is able to bind to metals. ], for example, has been investigated for use in treating ],<ref>{{cite journal| vauthors = Bach I, Kumberger O, Schmidbaur H |title = Orotate complexes. Synthesis and crystal structure of lithium orotate(—I) monohydrate and magnesium bis octahydrate|journal = ]|year = 1990|volume = 123|issue = 12|pages = 2267–2271|doi = 10.1002/cber.19901231207}}</ref><ref>{{cite journal | vauthors = Sartori HE | title = Lithium orotate in the treatment of alcoholism and related conditions | journal = Alcohol | volume = 3 | issue = 2 | pages = 97–100 | year = 1986 | pmid = 3718672 | doi = 10.1016/0741-8329(86)90018-2 }}</ref> and complexes of ], ], ], and ] are known.<ref name ="orotate salts" /> The pentahydrate nickel orotate ] converts into a polymeric trihydrate upon heating in water at 100 °C.<ref name ="orotate salts">{{cite journal | vauthors = Plater MJ, Foreman MR, Skakle JM, Howie RA | title = Hydrothermal crystallisation of metal (II) orotates (M= nickel, cobalt, manganese or zinc). Effect of 2, 2-bipyridyl, 2, 2-dipyridyl amine, 1-methyl-3-(2-pyridyl) pyrazole, phenanthroline and 2,9-dimethyl-1,10-phenanthroline upon structure. | journal = Inorganica Chimica Acta | date = April 2002 | volume = 332 | issue = 1 | pages = 135–145 | doi = 10.1016/S0020-1693(02)00728-4 | url = }}</ref><ref>{{cite journal| vauthors = Plater MJ, Foreman MR, Skakle JM, Howie RA |title = CCDC 189770 – Catena-((μ<sub>2</sub>-1,2,3,6-tetrahydro-2,6-dioxopyrimidine-4-carboxylato-N,O,O')-triaqua-nickel(ii))|journal = ]|year = 2002|doi = 10.5517/cc6cgmm}}</ref><ref>{{cite journal| vauthors = Karipides AN, Thomas B |journal = ]|year = 1986|volume = C42|pages = 1705–1707|title = The structures of tetraaqua(uracil-6-carboxylate)zinc(II) monohydrate (''A'') and tetraaqua(uracil-6-carboxylato)nickel(II) monohydrate (''B'')| issue=12 |doi = 10.1107/S0108270186090856}}</ref> Crystals of the trihydrate can be obtained by hydrothermal treatment of nickel(II) acetate and orotic acid. When the reactions are run with bidentate nitrogen ligands such as 2,2'-] present, other solids can be obtained. |
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== Pathology == |
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Orotic acid can be mutagenic (causes ]s) in mammalian somatic cells. It is also mutagenic for bacteria and or yeast. |
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A buildup of orotic acid can lead to ] and acidemia.<ref>{{cite journal | vauthors = Balasubramaniam S, Duley JA, Christodoulou J | title = Inborn errors of pyrimidine metabolism: clinical update and therapy | journal = Journal of Inherited Metabolic Disease | volume = 37 | issue = 5 | pages = 687–698 | date = September 2014 | pmid = 25030255 | doi = 10.1007/s10545-014-9742-3 | s2cid = 25297304 | authorlink3 = John Christodoulou (geneticist) }}</ref> It may be a symptom of an increased ] load due to a ], such as a ]. |
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In ], an X-linked inherited and the most common urea cycle disorder, excess carbamoyl phosphate is converted into orotic acid. This leads to an increased serum ammonia level, increased serum and urinary orotic acid levels and a decreased serum ] level. This also leads to an increased urinary orotic acid excretion, because the orotic acid is not being properly utilized and must be eliminated. The hyperammonemia depletes alpha-ketoglutarate leading to the inhibition of the ] (TCA) decreasing ] (ATP) production. |
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Orotic aciduria is a cause of megaloblastic anaemia. |
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==See also== |
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* ] |
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==References== |
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== Biochemistry == |
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{{Reflist|2}} |
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Orotic acid is a precursor to a RNA base, uracil. <ref>{{cite journal | vauthors = Ashihara H, Stasolla C, Loukanina N, Thorpe TA| doi=10.1034/j.1399-3054.2000.108001025.x | title=Purine and pyrimidine metabolism in cultured white spruce (''Picea glauca'') cells: Metabolic fate of <sup>14</sup>C-labeled precursors and activity of key enzymes | year=2000 | journal=Physiologia Plantarum | volume=108 | pages=25–33 }}</ref> The ] of ]s has a higher concentration of orotic acid than that of a non smoking ]. It is reasoned that the smoking causes the pyrimidine biosynthesis process in the mother to be altered thus causing the orotic acid concentration to increase.<ref>{{cite journal | vauthors = Karatas F | title = An investigation of orotic acid levels in the breastmilk of smoking and non-smoking mothers | journal = European Journal of Clinical Nutrition | volume = 56 | issue = 10 | pages = 958–960 | date = October 2002 | pmid = 12373615 | doi = 10.1038/sj.ejcn.1601420 | s2cid = 29181790 }}</ref> |
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==External links== |
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* {{MeshName|Orotic+Acid}} |
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A modified orotic acid (5-fluoroorotic acid) is toxic to ]. The mutant yeasts which are resistant to 5-fluoroorotic acid require a supply of ].<ref>{{cite journal | doi=10.2323/jgam.39.303 | title=Isolation of ''Phaffia rhodozyma'' auxotrophic mutants by enrichment methods | year=1993 | vauthors = Adrio JL, Veiga M, Casqueiro J, López M, Fernández C | journal=The Journal of General and Applied Microbiology | volume=39 | issue=3 | pages=303–312 | s2cid=84498320 | doi-access=free }}</ref> |
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{{Nucleotide metabolism intermediates}} |
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== See also == |
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* ] |
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* ] |
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== References == |
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{{pharma-stub}} |
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{{Reflist}} |
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== Further reading == |
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{{refbegin}} |
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* {{cite journal | doi = 10.1021/ja01652a056| title = Potential Metabolic Antagonists of Orotic Acid: 6-Uracilsulfonamide and 6-Uracil Methyl Sulfone| journal = Journal of the American Chemical Society| volume = 76| issue = 23| pages = 6052–6054| year = 1954| vauthors = Greenbaum SB }} |
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{{refend}} |
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== External links == |
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{{Commons category|Orotic acid}} |
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* {{MeshName|Orotic+Acid}} |
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{{Nucleotide metabolism intermediates}} |
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{{DEFAULTSORT:Orotic Acid}} |
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