Orotic acid is a pyrimidinedione and a carboxylic 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 synthesized in the body via a mitochondrial enzyme, dihydroorotate dehydrogenase or a cytoplasmic enzyme of Pyrimidine metabolism, 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 dihydroorotate dehydrogenase, where it later combines with phosphoribosyl pyrophosphate (PRPP) to form Orotidine 5'-monophosphate, 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.

Chemistry

Orotic acid is a Bronsted acid and the anion (orotate) is able bind to metals. For example it forms a pentahydrate complex with nickel. On heating in water at 100 oC the pentahydrate is converted into polymeric trihydrate.M.J.Plater, M.R.St.J.Foreman, J.M.S.Skakle, R.A.Howie CCDC 189770: Experimental Crystal Structure Determination, 2002, DOI: 10.5517/cc6cgmm 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'-bipyridine present other solids can be obtained.

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 transcarbamylase 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. Orotic aciduria is a cause of megaloblastic anaemia.

References

External links

* {{DEFAULTSORT:Orotic Acid Pyrimidinediones Enoic acids

Synthesis

Chemistry

Pathology

See also

References

Further reading

External links