Orotic acid

Orotic acid

Systematic (IUPAC) name
1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Identifiers
CAS Registry Number	65-86-1 Y
ATC code	None
PubChem	CID 967
DrugBank	DB02262 N
ChemSpider	942 N
UNII	61H4T033E5 N
KEGG	C00295 N
Chemical data
Formula	C5H4N2O4
Molecular mass	156.10 g/mol
SMILES O=C(O)\C1=C\C(=O)NC(=O)N1
InChI InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)  N Key:PXQPEWDEAKTCGB-UHFFFAOYSA-N  N
N (what is this?)  (verify)

Orotic acid is a heterocyclic compound and an acid; it is also known as pyrimidinecarboxylic acid. Historically it was believed to be part of the vitamin B complex and was called vitamin B₁₃, but it is now known that it is not a vitamin.

The compound is manufactured in the body via a mitochondrial enzyme, dihydroorotate dehydrogenase.^[1] or a cytoplasmic enzyme of pyrimidine synthesis pathway. It is sometimes used as a mineral carrier in some dietary supplements (to increase their bioavailability), most commonly for lithium orotate.

Synthesis

Dihydroorotate is synthesized to orotic acid by the enzyme dihydroorate dehydrogenase, where it later combines with phosphoribosyl pyrophosphate (PRPP) to form orotidine-5'-monophosphate (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.^[2]

Safety

Orotic acid can be mutagenic in mammalian somatic cells. It is also mutagenic for bacteria and yeast.^[3]

Pathology

A buildup of orotic acid can lead to orotic aciduria and acidemia. It may be a symptom of an increased ammonia load due to a metabolic disorder, such as a urea cycle disorder.

In ornithine transcarbamoylase deficiency, 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 blood urea nitrogen 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 tricarboxylic acid cycle (TCA) decreasing adenosine triphosphate (ATP) production.

See also

• Magnesium orotate
• Pyrimidine biosynthesis

References

External links

Wikimedia Commons has media related to Category:Orotic acid.

• Orotic Acid at the US National Library of Medicine Medical Subject Headings (MeSH)
• Greenbaum, Sheldon B. (1954). "Potential Metabolic Antagonists of Orotic Acid: 6-Uracilsulfonamide and 6-Uracil Methyl Sulfone1". Journal of the American Chemical Society 76 (23): 6052. doi:10.1021/ja01652a056.