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 manufactured in the body via a mitochondrial enzyme, dihydroorotate dehydrogenase or a cytoplasmic enzyme of pyrimidine synthesis pathway. It is sometimes used as a mineral carrier in some dietary supplements, most commonly for lithium orotate.
Synthesisis synthesized to orotic acid by the enzyme dihydroorotate dehydrogenase, where it later combines with phosphoribosyl pyrophosphate to form orotidine-5'-monophosphate. 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.
PathologyA 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 decreasing adenosine triphosphate production.
Orotic aciduria is a cause of megaloblastic anaemia.